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7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 118
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
11
Comparative study between cardioprotective effects
of intermittent antegrade blood cardioplegia with
terminal warm blood reperfusion (hot-shot) versus
intermittent antegrade blood cardioplegia in
pediatric cardiac surgery
Hussein H Sabri FRCA Samia I Sharaf MD Abla A Saab MD
Mohammed Saleh MSc
Department of Anesthesiology Intensive Care and Pain Management
Faculty of Medicine Ain shams University Cairo
Abstract
Background Terminal warm blood cardioplegia (hot-shot) has been shown to enhance
myocardial protection in adult cardiac surgery The aim of current study is to evaluateterminal warm cardioplegic blood reperfusion compared to conventional reperfusion to
determine whether it has a beneficial cardioprotective effect during pediatric cardiac
surgery Methods This prospective study was carried out in Ain Shams University
Hospital on sixty children scheduled for pediatric cardiac surgery Patients were
randomly allocated into 2 equal groups Control group (C) 30 patients received
intermittent antegrade cold blood cardioplegia Hot-shot group (HS) 30 patients
received intermittent antegrade cold blood cardioplegia with terminal warm blood
reperfusion just before declamping We traced and compared the effect of warm
cardioplegic blood reperfusion versus conventional reperfusion on clinical outcome
parameters myocardial oxygen and lactate extraction ratio after declamping and serum
level of cardiac troponin I Results This study demonstrated higher percentage of
spontaneous defibrillation into sinus rhythm in hot-shot group when compared to
control group (767 versus 333 respectively) lower level of inotropic support
required for weaning from CBP in hot-shot group when compared to control group
(44plusmn55 versus 105plusmn65 respectively) lower level of inotropic support required in the
ICU in hot-shot group when compared to control group ( 754plusmn612 versus 1225plusmn1032
respectively) less duration of inotropic support required in the ICU in hot-shot group
when compared to control group (95plusmn72 hours versus 149plusmn118 hours respectively)
Myocardial lactate extraction ratio was significantly elevated at all studied time
interval in hot-shot group when compared to control group lower level of Serum
troponin I at 4 hours after declamping in -shot group when compared to control group
(132plusmn80 ngml versus 313plusmn231 ngml) lower level of Serum troponin I at 8 hours
after declamping in hot-shot group when compared to control group (100 plusmn 58ngml
versus 191plusmn 115ngml) Conclusions This study demonstrated that intermittent cold
blood cardioplegia with terminal warm blood cardioplegia offered favorable effect on theclinical outcome parameters in term of higher percentage of spontaneous defibrillation
into sinus rhythm and lower level of inotropic support in comparison to intermittent
cold blood cardioplegia Moreover intermittent cold blood cardioplegia with terminal
warm blood cardioplegia accelerated recovery of aerobic metabolism and reduced the
myocardial damage following ischemia reperfusion injury
Keywords terminal warm blood cardioplegia bullHot-shot bull pediatric myocardialpreservation
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
12
Introduction
In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital
heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-
tection has become of great interestto cardiac anesthetists who should
tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater
safety in performing complex con-genital heart repairs
Despite major advances in the
technical aspects of surgical repairof congenital heart diseases peri-
operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac
damage from inadequate myo-cardial protection can prolong
hospital stay and result in delayedmyocardial fibrosis leading to
cardiac dysfunction months to years
later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term
outcome with surgical correction
Advances in cardioplegic techni-ques include intermittent ante-
grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al
1986 Caputo et al 1998)
However because of structuralfunctional and biochemical diff-
erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to
pediatric cardiac practice withoutevident base (Toyoda et al 2003
Modi et al 2004)
The aim of the current study is
to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac
practice in comparison to inter-
mittent antegrade cold bloodcardioplegia
Patients and methods
After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained
from the parents of each child
Methodology
Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were
enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)
thirty patients submitted forcorrection of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
Study group [Hot-shot]
(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
with terminal warm cardioplegic
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids
blood plasma and other drugs
Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial
blood samples were taken for
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
15
Table (1) Components added to crystalloid solution per liter
KCl 40 mmol L-1
NaHCO3 40 mmol L-1
Lidocaine 100 mg L-1
Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio
pH 76
Hematocrit 17-22
K + 20 mmol L-1
Na+ 150 mmol L-1
Cl+ 150 mmol L-1
Ca2+ 2 mmol L-1
Osmolaritv 380 mOsm L-1
Weaning of cardiopul-
monary bypass After completion
of the surgical repair rewarming
was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp
Ventricular distention during re-perfusion was avoided by regu-
lation of systemic venous return
and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation
persisted Pacing the heart was
applied if there was second orthird degree heart block orintractable sinus bradycardia
Once optimal heart rate
electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload
CBP was gradually stopped If
systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice
inotrope [dobutamine infusion
starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was
ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1
min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient
At the end of bypass
protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The
chest was then closed in routine
fashion once meticulous hemos-tasis was achieved
Postoperative care Patient
admitted to pediatric cardiac sur-
gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were
based on unit protocol hemody-
namic status and clinical judgment
Parameters of the study
Assessment of clinical outcomeIntraoperative and postoperative
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Comparison of cardioprotective effects Hussein Sabri et al
12
Introduction
In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital
heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-
tection has become of great interestto cardiac anesthetists who should
tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater
safety in performing complex con-genital heart repairs
Despite major advances in the
technical aspects of surgical repairof congenital heart diseases peri-
operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac
damage from inadequate myo-cardial protection can prolong
hospital stay and result in delayedmyocardial fibrosis leading to
cardiac dysfunction months to years
later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term
outcome with surgical correction
Advances in cardioplegic techni-ques include intermittent ante-
grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al
1986 Caputo et al 1998)
However because of structuralfunctional and biochemical diff-
erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to
pediatric cardiac practice withoutevident base (Toyoda et al 2003
Modi et al 2004)
The aim of the current study is
to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac
practice in comparison to inter-
mittent antegrade cold bloodcardioplegia
Patients and methods
After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained
from the parents of each child
Methodology
Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were
enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)
thirty patients submitted forcorrection of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
Study group [Hot-shot]
(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
with terminal warm cardioplegic
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids
blood plasma and other drugs
Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial
blood samples were taken for
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Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
15
Table (1) Components added to crystalloid solution per liter
KCl 40 mmol L-1
NaHCO3 40 mmol L-1
Lidocaine 100 mg L-1
Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio
pH 76
Hematocrit 17-22
K + 20 mmol L-1
Na+ 150 mmol L-1
Cl+ 150 mmol L-1
Ca2+ 2 mmol L-1
Osmolaritv 380 mOsm L-1
Weaning of cardiopul-
monary bypass After completion
of the surgical repair rewarming
was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp
Ventricular distention during re-perfusion was avoided by regu-
lation of systemic venous return
and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation
persisted Pacing the heart was
applied if there was second orthird degree heart block orintractable sinus bradycardia
Once optimal heart rate
electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload
CBP was gradually stopped If
systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice
inotrope [dobutamine infusion
starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was
ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1
min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient
At the end of bypass
protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The
chest was then closed in routine
fashion once meticulous hemos-tasis was achieved
Postoperative care Patient
admitted to pediatric cardiac sur-
gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were
based on unit protocol hemody-
namic status and clinical judgment
Parameters of the study
Assessment of clinical outcomeIntraoperative and postoperative
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids
blood plasma and other drugs
Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial
blood samples were taken for
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Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
15
Table (1) Components added to crystalloid solution per liter
KCl 40 mmol L-1
NaHCO3 40 mmol L-1
Lidocaine 100 mg L-1
Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio
pH 76
Hematocrit 17-22
K + 20 mmol L-1
Na+ 150 mmol L-1
Cl+ 150 mmol L-1
Ca2+ 2 mmol L-1
Osmolaritv 380 mOsm L-1
Weaning of cardiopul-
monary bypass After completion
of the surgical repair rewarming
was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp
Ventricular distention during re-perfusion was avoided by regu-
lation of systemic venous return
and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation
persisted Pacing the heart was
applied if there was second orthird degree heart block orintractable sinus bradycardia
Once optimal heart rate
electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload
CBP was gradually stopped If
systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice
inotrope [dobutamine infusion
starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was
ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1
min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient
At the end of bypass
protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The
chest was then closed in routine
fashion once meticulous hemos-tasis was achieved
Postoperative care Patient
admitted to pediatric cardiac sur-
gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were
based on unit protocol hemody-
namic status and clinical judgment
Parameters of the study
Assessment of clinical outcomeIntraoperative and postoperative
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
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Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
15
Table (1) Components added to crystalloid solution per liter
KCl 40 mmol L-1
NaHCO3 40 mmol L-1
Lidocaine 100 mg L-1
Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio
pH 76
Hematocrit 17-22
K + 20 mmol L-1
Na+ 150 mmol L-1
Cl+ 150 mmol L-1
Ca2+ 2 mmol L-1
Osmolaritv 380 mOsm L-1
Weaning of cardiopul-
monary bypass After completion
of the surgical repair rewarming
was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp
Ventricular distention during re-perfusion was avoided by regu-
lation of systemic venous return
and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation
persisted Pacing the heart was
applied if there was second orthird degree heart block orintractable sinus bradycardia
Once optimal heart rate
electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload
CBP was gradually stopped If
systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice
inotrope [dobutamine infusion
starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was
ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1
min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient
At the end of bypass
protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The
chest was then closed in routine
fashion once meticulous hemos-tasis was achieved
Postoperative care Patient
admitted to pediatric cardiac sur-
gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were
based on unit protocol hemody-
namic status and clinical judgment
Parameters of the study
Assessment of clinical outcomeIntraoperative and postoperative
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
15
Table (1) Components added to crystalloid solution per liter
KCl 40 mmol L-1
NaHCO3 40 mmol L-1
Lidocaine 100 mg L-1
Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio
pH 76
Hematocrit 17-22
K + 20 mmol L-1
Na+ 150 mmol L-1
Cl+ 150 mmol L-1
Ca2+ 2 mmol L-1
Osmolaritv 380 mOsm L-1
Weaning of cardiopul-
monary bypass After completion
of the surgical repair rewarming
was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp
Ventricular distention during re-perfusion was avoided by regu-
lation of systemic venous return
and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation
persisted Pacing the heart was
applied if there was second orthird degree heart block orintractable sinus bradycardia
Once optimal heart rate
electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload
CBP was gradually stopped If
systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice
inotrope [dobutamine infusion
starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was
ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1
min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient
At the end of bypass
protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The
chest was then closed in routine
fashion once meticulous hemos-tasis was achieved
Postoperative care Patient
admitted to pediatric cardiac sur-
gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were
based on unit protocol hemody-
namic status and clinical judgment
Parameters of the study
Assessment of clinical outcomeIntraoperative and postoperative
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
17
O2 content CS oxygen content incoronary sinus blood sample
Myocardial lactate extraction
ratio was calculated according to
the following equation
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
18
Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards
cardiopulmonary bypass time (P
value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)
Table 3 Patientsrsquo characteristics and intraoperative dataControl group
No =30
Hot-shot group
No =30P value
Age (month) 175 plusmn 56 181 plusmn 57 0716
Sex (MF) 1416 1614 0797
Weight (Kg) 141 plusmn 38 148 plusmn 42 0481
Pathology (n)
Acyanotic 17 19 ASD 6 7
VSD 7 9
CAVSD 4 3
Cyanotic 13 11
TOF 7 6
DORV- PS 6 5
CBP (min) 643plusmn 259 679plusmn 288 0621
Ao Cx (min) 378plusmn 169 382plusmn 171 0916
Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749
Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect
VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis
CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp
Fisherrsquos exact test for sex Chi-square test for pathology
Parameters of the study
Clinical outcome parameters
Intraoperative parametersThere was a significant difference
between both study groups after
declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of
control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group
(P value was 0002) (Table 4)
As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no
significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P
value was 0748) (Table 4)
As regards intraoperative
inotropes there was a significantdifference between both studygroups as regards number of
patients who required inotropes
for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group
versus 24 patients of control group
(P value was 0015) (Table 4)
There was also a significantdifference between both groups as
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
19
regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot
group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)
Table 4 Intraoperative clinical outcome variablesControl
group
No =30
Hot-shot
group
No =30
P
value
Spontaneous defibrillation into sinusrhythm n ()
10 (333) 23 (767) 0002
Electrical defibrillation n () 20 (667) 7 (233) 0002
Requirement of pacing for weaning fromCBP n ()
7 (233) 5 (167) 0748
Requirement of intraoperative inotrope n
()24 (80) 14 (467) 0015
Inotrope score required for weaning from
CBP Mean plusmn SD 105plusmn
65 44plusmn
55 lt0001
n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t
test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous
defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope
Postoperative parameters
There was a significant
difference between both studygroups as regards inotropes
required in the intensive careInotropes were required in 14
patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score
in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)
Inotrope duration was 95plusmn72hrsin hot-shot group versus
149plusmn118hrs in control group (Pvalue was 0039) (Table 5)
As regards duration ofmechanical ventilation there was
no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38
hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)
As regards duration of ICU
stay there was no significantdifference between both study
groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control
group (P-value was 0099) (Table
5)
There was no significantdifference between both study
groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative
deaths in control group (P valuewas 0237) (Table 5)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1018
Comparison of cardioprotective effects Hussein Sabri et al
20
Table 5 Postoperative clinical outcome parametersControl
group
No =30
Hot-shot
group
No =30
P
value
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
983091983088
983091983093
983092983088
983092983093
983093983088
983093983093
983094983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137
983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent
95 confidence interval
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1118
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1118
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
21
As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the
different studied time intervals
throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7
Fig 2)
Table 7 Myocardial lactate extraction ratio (M lactate ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P-
value
M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027
M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042
M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024
M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001
M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001
Mean plusmn SD P value is significant when Plt005 unpaired t-test
983085983091983088
983085983090983093
983085983090983088
983085983089983093
983085983089983088
983085983093
983088
983093
983089983088
983089983093
983090983088
983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156
983145 983151 983150 983154 983137 983156 983145 983151 983077
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars
represent 95 confidence interval P-value is significant when Plt005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
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Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
983088
983093
983089983088
983089983093
983090983088
983090983093
983091983088
983091983093
983092983088
983092983093
983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155
983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137
983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081
983139983151983150983156983154983151983148 983143983154983151983157983152
983144983151983156983085983155983144983151983156 983143983154983151983157983152
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Toyoda et al (2003) examined
the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood
cardioplegia solution was composed
by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood
cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal
warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the
protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-
ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618
Comparison of cardioprotective effects Hussein Sabri et al
26
dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of
myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda
The current study is inagreement with Modi et al
(2004) who compared the use of
crystalloid cardioplegia cold blood
cardioplegia and cold blood
cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical
correction The efficacy of the 3
techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular
metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic
patients blood cardioplegia withhot-shot reduced metabolic injury
compared with cold crystalloidcardioplegia They also showed
that cold blood cardioplegia wason its own better than crystalloid
but not as good as cold bloodcardioplegia with hot-shot
Young et al (1997) failed to
demonstrate statistical advantage
for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-
tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood
cardioplegia in congenital heartsurgery when only antegrade
hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique
with substrate enrichment may bebeneficial for pediatric population
As conclusion the result of
the current study showed that theuse of cardioplegia with hot-shot
provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population
These criteria include warm
blood accelerates recovery oftemperature-dependent enzymatic
and metabolic function highpotassium concentration prolongs
electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema
References
1 Allen BS Okamoto F
Buckberg GD Bugyi H
Young H Leaf J
Beyersdorf F Sjostrand F
and Maloney JV Jr
Studies of controlledreperfusion after ischemiaXV Immediate functional
recovery after six hours of
regional ischemia by careful
control of conditions ofreperfusion and compositionof reperfusate J Thorac
Cardiovasc Surg 1986 92(3Pt 2) 621-35
2 Allen BS Current Conceptsin Pediatric Myocardial
Protection In Salerno TA and
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
27
Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29
3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the
solution Semin Thorac
Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54
4 Bull C Cooper J and
Stark J Cardioplegicprotection of the childrsquos
heart J Thorac Cardio-vasc
Surg 1984 88(2) 287-93
5 Caputo M Dihmis WC
Bryan AJ Suleiman MS
and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients
undergoing coronary arterybypass surgery Eur J
Cardiothorac Surg 199813(5) 559-64
6 Follette DM Fey K
Buckberg GD Helly JJ Jr
Steed DL Foglia RP and
Maloney JV Jr Reducingpostischemic damage by
temporary modifi-cation ofreperfusate calcium
potassium pH and
osmolarity J ThoracCardiovasc Surg 1981 82 (2)
221-38
7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995
60 (3) 839-842
8 Immer FF Stocker FP
Seiler AM Pfammatter JP
Printzen G and Carrel TP
Comparison of troponin-I and
troponin-T after pediatriccardiovascular opera-tion
Ann Thorac Surg 1998 66 (6)2073-7
9 Krause EG Pfeiffer D
Wollen-berger U and
Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an
approach implicating a peri-
operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)
Ischemia-reperfusion in
cardiac surgery 1st editionKluwer Academic 1993 317-33
10 Kronon MT Allen BS
Rahman S Wang T
Tayyab NA Bolling KS and
Ilbawi MN Reducingpostischemic reper-fusion
damage in neonates using a
terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770
11 Modi P Suleiman MS
Reeves B Pawade A Parry
AJ Angelini GD and
Caputo M Myocardial
metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818
Comparison of cardioprotective effects Hussein Sabri et al
28
12 Nomura F Forbess JM
and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in
neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7
13 Teoh KH Christakis GT
Weisel RD Fremes SE
Mickle DA Romaschin AD
Harding RS Ivanov J
Madonik MM Ross IM et
al Accelerated myocardial
metabolic recovery with
terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)
888-95
14 Toyoda Y Yamaguchi M
Yoshimura N Oka S and
Okita Y Cardioprotectiveeffects and the mechanisms of
terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125
(6) 1242-51
15 Wernovsky G Wypij D
Jonas RA Mayer JE Jr
Hanley FL Hickey PR
Walsh AZ Chang AC
Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial
switch operation in neo-natesand infants A comparison of
low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-
35
16 Young JN Choy IO SilvaNK Obayashi DY and
Barkan HE Antegrade cold
blood cardioplegia is not
demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J
Thorac Cardiovasc Surg1997 114(6) 1002-9