Effects Cycle Length Cardiac Refractory Periods in Mancirc.ahajournals.org/content/circulationaha/49/1/32.full.pdf · CYCLE LENGTHAND CARDIAC REFRACTORY PERIODS Table 1 Summary of

$Page 1: Effects Cycle Length Cardiac Refractory Periods in Mancirc.ahajournals.org/content/circulationaha/49/1/32.full.pdf · CYCLE LENGTHAND CARDIAC REFRACTORY PERIODS Table 1 Summary of$
The Effects of Cycle Lengthon Cardiac Refractory Periods

in Man

By PABLO DENES, M.D., DELON WU, M.D., RAMESH DHINGRA, M.D.,RAYMOND J. PIETRAS, M.D, AND KENNETH M. ROSEN, M.D.

SUMMARYThe effects of pacing-induced changes in cycle length on the refractory periods of the atrium,

A-V node and His-Purkinje system were studied in 24 patients using the extra stimulus technique.Refractory period determinations were made at two or more cycle lengths in all patients. Slopesrelating cycle length and refractory periods were calculated using the least squares method.

Both the effective and functional refractory periods (ERP and FRP) of the atrium shortenedwith decreasing cycle lengths, with a mean slope of +0.155 and +0.129 respectively. A-V nodalERP lengthened (mean slope, -0.177) while A-V nodal FRP shortened slightly (mean slope,+0.126). Bundle branch refractory periods as well as relative refractory periods of the His-Pur-kinje system also decreased, with mean slopes of +0.270 and +0.360, respectively. The ERP ofthe A-V node at any cycle length was related to the A-H at that cycle length (r= +0.646,P < 0.001).The responses of the human heart to changes in cycle length are generally similar to those

previously described in the animal laboratory. Such information contributes to our understandingof electrocardiographic phenomena such as aberrant conduction.

Additional Indexing Words:His bundle electrogramFunctional refractorv period

Premature atrial impulsesRelative refractory period

Effective refractory periodAberrant conduction

IN ISOLATED HEART TISSUE, as cycle lengthchanges, action potential durations and refrac-

tory periods are altered.' Mendez et al., workingwith intact denervated canine hearts, noted that thefunctional refractory periods of the atrium, A-Vnode, His bundle, and bundle branches shortenedas cycle length was decreased.2 These changes wereleast apparent in the A-V node and most striking inthe His-Purkinje system.The purpose of the present study was to examine

the effect of pacing-induced changes in cycle length

From the Section of Cardiology, Department of Medicine,Abraham Lincoln School of Medicine and the University ofIllinois College of Medicine, and the West Side VeteransAdministration Hospital, Chicago, Illinois.

Supported in part by NIH contract 71-2478 under theMyocardial Infarction Program and West Side VeteransAdministration Hospital BIS funds.

Address for reprints: Kenneth M. Rosen, M.D., Universityof Illinois Hospital, P. 0. Box 6998, Chicago, Illinois60680.

Received May 4, 1973; revision accepted for publicationAugust 30, 1973.

32

on the refractory periods of the atrium, A-V node,and His-Purkinje system in man.

MethodsRefractory periods were determined in 24 patients

during diagnostic cardiac catheterization. All patientswere in sinus rhythm and had normal QRS duration(0.10 sec or less) and normal conduction intervals asdetermined by His bundle recording technique.3 Themean age of the patients was 41 years (range 15-77),and there were 18 males and six females. Clinical andelectrocardiographic data as well as control conductionintervals are summarized in table 1. Only two patientshad received cardioactive drugs within the week priorto study (procaine amide in patient 4 and digoxin inpatient 8). Both drugs were discontinued 48 hoursprior to study in these latter two patients.

His bundle electrograms were recorded with atripolar catheter placed close to the tricuspid valve.4Atrial electrograms were recorded through two elec-trodes of a quadripolar catheter positioned fluoroscopi-cally against the lateral wall of the high right atrium.The remaining two electrodes were used for atrialpacing. Interelectrode distances were one centimeter.Recordings were obtained on a multichannel oscillo-scopic recorder (Electronics for Medicine, DR-16, WhitePlains, New York) at paper speeds of 100 and 200

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CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS

Table 1

Summary of Clinical Data, Electrocardiologic Data and Control Conduction Intervals for 24 Study Patients

Mean frontalPatient Age Cardiovascular Sinus rate QRS duration QRS axis ECG P-A A-l- H-Vnumber (years) Sex diagnosis (beats/min) (sec) (degrees) diagnosis (msec) (msec) (msec)

1 67 M HHD 90 0.09 -45 LVH 20 65 352 35 M HHD 74 0.09 + 5 ST-T 53 1iO 403 19 M No HI) 75 0.08 +30 WNL 19 100 364 42 F ASHD 58 0.09 +20 ST-T 40 92 345 54 M ASHD 103 0.08 +20 ST-T 15 90 536 26 m JIHD 96 0.10 +60 LVH 20 130 3507 13; M ASD secundum 94 0.08 +80 rr' in V1 20 6) 338 52 M ASHD 72 0.08 +30 ST-T 35 100 459 33 F R HD 78 0.08 +60 LVH 33 86 3.310 15 M No HD 65 0.10 +60 WNL 25 71 4811 67 M PMI) 35 0.09 -20 LVH 40 90 3012 19 M ASD) secundtum 78 0.10 +100 rr' in V1 25 124 4313 38 m No HD 85 0.08 0 WNL 15 95 3014 35 F ASHD 110 0.08 -15 WNL 28 70 4013 13 M No HD 92 0.06 +60 ST-T 28 73 4316 40 M ASHD 87 0.06 +40 WNL 21 104 2817 56 F Cale. peric. 84 0.07 +60 ST-T 35 1]13 3218 24 M PDA 81 0.09 +45) WNL 27 91 3719 23 M Coarct. 86 0.09 +20 LVH 19 103 3120 77 M HHI) 64 0.09 -10 ST-T 15 83 382'1 48 F No HD 73 0.09 +60 WNL 21 90 3422 19 M No HD 75 0.07 +60 WNL 37 76 4823 72 M ASHD 5a6 0.09 +10 ST-T 25 80 4324 47 F RHD 93 0.08 +50 WNL 32 100 40

Abbreviations: P-A = interval between the beginning of the P wave and the atrial electrogram as recorded by the His bundlecatheter; A-H = interval between the atrial electrogram and the His deflection; H-V = interval between the His bundle electro-gram and initiation of ventricular depolarization; HHD = hypertensive heart disease; HD = heart disease; ASHD = arterio-sclerotic heart disease; RHD = rheumatic heart disease; PDA = patent ductus arteriosus; ASD = atrial septal defect; PMD= primary myocardial disease; Coarct. = coarctation of the aorta; Calc. peric. = calcific pericarditis; WNL = within normallimits; LVH = left ventricular hypertrophy; ST-T = nonspecific ST and T wave changes.

mm/ sec. Stimuli were approximately twice diastolicthreshold, 2 msec in duration, and delivered by aprogrammable digital stimulator (manufactured by M.Bloom, Philadelphia, Pa.).

Refractory periods were measured with the techniqueof extra stimulus. The extra stimulus (S2) wasintroduced after every tenth driven (S,) or spontaneousbeat. S1-S2 intervals were decreased in 10-20 msecdecrements in successive test cycles.5 Refractoryperiods were first determined during either sinusrhythm or at the slowest paced rate producing stableatrial capture. All patients had refractory periodsdetermined at two or more cycle lengths. To examinethe effect of cycle length on refractory periods, slopeswere calculated by the least squares method forindividual patients. Mean slopes (± SEM) were thencalculated for refractory periods of the atria, A-V node,and His-Purkinje system. The term "significantly" wasdefined as a change in refractory period, statisticallydifferent from no change (zero slope). The relationbetween A-V nodal conduction time (A-H) andeffective refractory period was analyzed using thecorrelation coefficient.

Atrial and A-V nodal refractory periods were alsoCirculation, Volume XLIX, January 1974

analyzed by computing means and ranges for threeabsolute ranges of cycle length. These were 850 to 600msec (heart rate of 70 to 100 beats/min), 599 to 460msec (101 to 130 beats/min), and 459 to 330 msec(131 to 180 beats/min).A-H and H-V intervals were measured as previously

described.5 A1, H1, and V1 represent the atrial, Hisbundle, and ventricular electrograms of either sponta-neous or driven beats. A2, H2, and V2 represent theatrial, His bundle, and ventricular electrograms inresponse to the extra stimulus (S2).The atrial effective refractory period (ERP) was the

longest S1-S2 interval in which atrial capture failed tooccur. At times the coupling interval of the teststimulus was too long to determine the ERP. When thisoccurred, the atrial ERP was designated as being lessthan the shortest S1-S2 tested. Atrial functionalrefractory period (FRP) was the shortest attainablepropagated A1-A2 interval.The A-V nodal ERP was the longest A1-A2 interval

which did not propagate to the His bundle. A-V nodalFRP was the shortest propagated Hr-H2 interval.The ERP of the His-Purkinje system was the longest

H1-H2 interval in which conduction to the ventricles

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Atr'ium

= ~~~~~~~~No.o f pa tients 11Mean slope +155S. D. .06S E.M. 062

400 500 600 700 800 900 1000Cycle length (msec)

W 400

E

(D° 350

° 300U

aW: 2500c

u 200

a

FAt r urm

Number of potients 11Mean slope 4.1 29

~~~~S. D .045S.E.M. .014

400 500 600 700 800 900 1000Cvele lenath (msec)

I-_

F

Figure 1

Left) The atrial effective refractory period as a function of cycle length in 11 patients. Right) The atrialfunctional refractory period as a function of cycle length in 11 patients. Each patient is represented asa series of connected dots.

failed to occur. This is identical to the ERP of theventricular specialized conduction system as defined byWit et al.5 The relative refractory period (RRP) of theHis-Purkinje system was defined as the longest H1-H2interval at which the H2-V2 interval becomes longerthan HV1, interval of spontaneous or driven beats.Prolongation of H2-V2 could reflect conduction delays inthe His bundle distal to the His bundle recording siteand/or delays in both bundle branches.The refractory period of a bundle branch was

considered the longest H1-H2 interval producing theappropriate electrocardiographic pattemn of completebundle branch block. This refractory period could be

A V Node Number of patients 14Mean slope -.177

S D .145S. E.M. .040

either relative, with the critical degree of bundle branchdelay necessary to produce a pattern of completebundle branch block, or effective, with total failure ofconduction in that bundle branch.

All determinations could not be obtained in allpatients or at every cycle length studied.

ResultsEffect of Cycle Length on Refractory Periods

Atrium. Atrial ERP was successfully measured atone or more cycle lengths in 23 patients (table 2).In patient nine, the extra stimulus was not brought

550

en

E 500

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AV Node

No. of patients 15Mean slope +.126S D. .17S.E.M. .045

l

L

400 500 600 700 800 900 1000Cycle length ( msec)

1 1400 500 600

Cycle

Figure 2

Left) The A-V nodal effective refractory period as a function of cycle length in 14 patients. Right) TheA-V nodal functional refractory period as a function of length in 15 patients. The crossed dotsrepresent the atriad functional refractory period in those instances where this exceeded the A-V nodaleffective refractory period. The actual value of the A-V nodal ERP can only be less than the atrialFRP at these points.

Circulation, Volume XLIX, January 1974

03506

°£3000a

o 250

0

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2 200

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(msec)

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His Purkinje System

Number ofpetients 6

,< . ~~~Meon s lope + .27

S. D. .109S. E. M. .044

L400 500 600 700

Cycle length

1

800(msec)

E

-o0

0-

0

E,

cr-

550r

500F

Bundle Branches

- ~Right BB

. .Left BB

450-

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Number of patients 7

350-

300 L

IL4900 1000

L400 500 600 700

Cycle length

Mean slope + .360

S.D. .173

S. E. M. .065

800 900 10(m sec)

Z00

Figure 3

Left) Relative refractory period of the His-Purkinje system as a function of cycle length in six patients.Right) Refractory period of the bundle branches as a function of cycle length in seven patients. Thecrossed dots represent the A-V nodal functional refractory period in those instances where this exceed-ed the His-Purkinje system relative refractory period.

in close enough to measure atrial ERP or FRP atany cycle length. For purposes of analysis, slopes ofthe relationship of atrial ERP to cycle length were

calculated for patients in whom four or more

recordings over a cycle length range not less than200 msec (11 patients) were made. The mean

slope SEM was +0.155 0.020 msec (figs. 1 and4). Thus, atrial ERP decreased significantly as cyclelength was shortened. The means and ranges ofatrial ERP for all 23 patients are given in table 3.

Atrial FRP was measured in 23 patients (table2). Slopes were calculated for all patients in whomfour or more recordings over a cycle length rangenot less than 200 msec (11 patients) were made.The mean slope SEM was +0.129 + 0.014 msec

(figs. 1 and 4). Thus, atrial FRP decreasedsignificantly as cycle length was shortened. Themeans and ranges for all 23 patients are given intable 3.A-V node. A-V node ERP could be determined in

18 patients (table 2). Slopes were calculated for allpatients in whom three or more determinations over

a cycle length range not less than 200 msec (14patients) were made. The values at which atrialFRP exceeded the A-V nodal ERP at the initial(longest) cycle length were also computed (pa-tients 8, 10, and 19) for calculation of the slopes,since A-V nodal ERP could only be less than thevalues indicated. The mean slope-+ SEM was

-0.177 + 0.040 (figs. 2 and 4). Thus, A-V nodal ERP


< -02

-04 -EE:mean

-06

ERF FRP ERP FRP RRP RP

ATRIUM A-V NODE HPS BB.

Figure 4

The effect of change in cycle length on the change in re-

fractory periods of the atrium, A-V node, and His-Purkinjesystem. Each point represents the mean slope of change inrefractory period related to change in cycle length forindividual patients. A positive value indicates that as cyclelength decreases refractory periods decrease. A negativevalue indicates that as cycle length decreases refractoryperiod increases. A zero value indicates no change in refrac-tory period despite change in cycle length. ARP = change inrefractory period (msec); ACL = change in cycle length(msec); ERP = effective refractory period; FRP = functionalrefractory period; RRP = relative refractory period; RP.=refractory period; HPS = His-Purkinje system; BB = bundlebranches. Mean SEM are indicated.

c)

0

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450-

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3501

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Table 2

Electrophysiological Data for 24 Patients*

Patient CL A ERP A FRP AVN ERP AVN FRP A-H BB RP HPSRRP

1 630 240 285 <28.5 43 15 55;)20 210 265 < 265 34,5 65)430 200 245 <245 325 65

2 640 270 305 345 430 120480 < 305 < 3153) 390 435 150

3 667 265 290 300 440 100043 265 285 335 500 110462 <24.5 <270 320 445) 120

4 85)0 230 285 285 420 105600 225 265 280 415 125490 235 29,5 315 415) 165

a 70 190 265 < 265 335 90 355R 355450 180 245 <245 330 100 <330 <330390 180 255 <255 330 100360 190 2.50 t

6 600 <270 <270 275 33i5 65450 190 225 275) 325 105400 195 25)0 275 - 105

7 600 195 210 280 415 80445 190 215 325 41.5 200

8t -790 250 265 <265 350 75 470R 425580 225) 235 310 375 100 395 380470 200 225 285 360 110 <360 <360420 200 235 305 350 110

9 667 <210 <215 320 430 1154;5 <245 <245 405 460 128

10 7615 290 310 <310 490 80560 290 310 335 520 110410 270 290 350 505 120480 260 270 370 400 255445 25)0 280 t

11 710 270 310 3653 450 100580 270 295 405 475 120480 <425 <4225 425 475 160

12 690 230 2.50 330 495 130o60 22,5 260 370 510 180510 180 260 365 475 220480 190 210 390 470 280440 190 215 t-360 180 205 t -

13 6150 210 260 260 465 100530 230 275 290 435 140430 200 260 320 400 160

14 480 190 223 <2225 <290 70 315R -390 200 225 <225 <305 100 <305

1.5 480 <263 <26.3) 270 3,50 100400 190 200 250 315 100

16 613) 215) 300 340 440 11552(0 230 280 3350 423 140445 203 275 365 405 140375 205 265) t

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Patient CL

17 675560510470444360

18 745690565480400380

19 755670522

20 720580485420380

21 870650550450

22 720680

23 1000640480420

24 620560470353

A ERP A FRP AVN ERP AVN FRP A-H BB RP HPS RRP

230 280 310 470 120230230195190180

220220210205205165

150160160

34,5335290285265

230200185190

190170

360300250230

220190180170

300260240240230

300275280275275240

230195195

365365340330330

310295260260

200190

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<230270265

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310295320310

<200<190

<390<340<305<295250280290t

460470470

410390380375370365

405390360

<395<365<350<335<335

385360330335

425370

<440<390<365<380

405400390

160195230

95100105130130140

105110125

100115145155150

80120135125

100115

95135155180

105125150

425L<390

460R405355340

<335

460R380

<330

520L400

<365

425<390

460390365350

<335

410370

<330

455400

<365

*All values are expressed in msec.tCL at which type I second degree block proximal to H was present.tThe ERP of the HPS was 395 msec at the CL of 790 msec in this patient. The FRP of the A-V node ex-ceeded the ERP of the HPS at a shorter CL.Abbreviations: CL = cycle length; A ERP = atrial effective refractory period; A FRP = atrial functional

refractory period; AVN ERP = A-V nodal effective refractory period; AVN FRP = A-V nodal ftnctionalrefractory period; A-H = interval between the atrial electrogram and the His deflection recorded by the Hisbundle catheter; BB RP = Bundle branch refractory period; Ri = indicates right bundle; L indicates leftbundle; anid HPS RRP = His-Purkinje System relative refractory period.

lengthened significantly as cycle length was short-ened. The means and ranges for all 18 patients aregiven in table 3.A-V nodal FRP could be measured in 21 patients

(table 2). Slopes were calculated for all patients inwhom three or more determinations over a cyclelength range of more than 200 msec (15 patients)were made. The mean slope ± SEM was +0.126 ±0.045 msec (figs. 2 and 4). Thus, A-V nodal FRP


decreased as cycle length was shortened. Meansand ranges for all 21 patients are given in table 3.A-V nodal conduction time (A,-H,) lengthened

in all patients as cycle length was shortened. Therelationship of A-V nodal conduction time toeffective refractory period was examined by plot-ting A,-H1 intervals against the ERP of the A-Vnode for each patient at all cycle lengths in whichboth were measured. A statistically significant

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Table 3

The Effective and Functional Refractory Period at Three Cycle Length Ranges for the Atriumand the A-V Node*

CL = 850-600 599-460 459-380HR = 70-100 101-130 131-180

ATRIUTMERP mean (range) 235 (150-360) 225 (160-335) 201 (165-285)Number of observations 25 29 23Number of patients 19 18 16FRP mean (range) 278 (190-390) 267 (195-365) 248 (195-330)Number of observations 23 29 23Number of patients 19 18 16

A-V NODEERP mean (range) 303 (250-365) 340 (265-425) 307 (275-365)Number of observations 16 29 9Number of patients 15 16 8FRP mean (range) 421 (350-495) 419 (330-520) 351 (313-415)Number of observations 23 31 11Number of patients 18 18 10

*All values are expressed in msec.Abbreviations: HR = heart rate, beats/mim; CL = cycle length in msec; ERP = effective refractory period;

FRP = functional refractory period.

correlation was found with an (r) value of +0.65(fig. 5). No similar relationship was found betweenA,-Hi and A-V nodal FRP.

His-Purkinfe system. The RRP of the His-Purkinje system could be measured in six patients(table 2). Slopes were calculated for all six patients.The values obtained at the longest cycle length inwhich A-V nodal FRP exceeded the RRP of the His-

AH vs AVN-ERP

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250

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100

r =+.646SEE=34D=< 001 0

0

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400 450

Figure 5

The relationship of A-V nodal conduction times (A-H) andeffective refractory periods. The A-V nodal conduction times(A-H) of driven stimuli are plotted against A-V nodal effec-tive refractory periods at the driven cycle length (AVN-ERP). Values of 54 cycle lengths from 18 patients are

plotted.

0

0

Purkinje system were also computed from therecordings of all patients for calculation of theslopes, since the RRP of the His-Purkinje systemcould only be less than the values indicated. Themean slope ± SEM was +0.270 ± 0.044 (figs. 3 and4). Thus, the RRP of the His-Purkinje systemshortened significantly as cycle length was de-creased.Bundle branch refractory periods could be

measured in seven patients (left bundle branch intwo and right bundle branch in five, table 2).Slopes were calculated as described for the His-Purkinje system for these patients. The meanslope + SEM was +0.36 ± 0.065 (figs. 3 and 4).Thus, bundle branch refractory periods decreasedsignificantly as cycle length was shortened.The ERP of the His-Purkinje system could be

measured in only one patient (patient 8) and was395 msec at a cycle length of 790 msec (table 2).

Relationship between Refractory Periodsof Different Cardiac Tissues

Atrial FRP vs A-V Nodal ERP. The A-V nodaleffective refractory period could not be measured insix patients because the atrial FRP was longer at allcycle lengths. In eight of the remaining 18 patients,the atrial FRP was equal to or exceeded the A-Vnodal ERP at the longest basic cycle length tested.In all eight cases this cycle length was greater than600 msec.A-V Nodal FRP vs His-Purkinje System Refrac-

tory Periods. The RRP of the His-Purkinje systemCirculation, Volume XLIX, January 1974

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exceeded the A-V nodal FRP in five out of tendeterminations (50%) at basic cycle lengths greaterthan 700 msee, in five out of 36 determinations(14%) between cycle lengths of 700 and 500 msec,and in two out of 25 determinations (7%) at cyclelengths less than 500 msec.The RP of the bundle branches exceeded the A-V

nodal FRP in five out of ten determinations (50%)at basic cycle lengths greater than 700 msec, in fiveout of 36 determinations (14%) between 500 and700 msec and in three out of 26 determinations(12%) at cycle lengths less than 500 msec.These relationships can be better visualized by

examining the values from recording a typicalpatient. Values from patient 8 are shown in figure 6.At a cycle length of 790 msec, the shortest attainableinterval between two atrial impulses that traversethe A-V node (H,-H2) was 350 msec (A-V nodalFRP). Impulses that propagated through the node

J.G. REFRACTORY PERIODS

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AVERP

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500 600 700

CYCLE LENGTH (msec)

800

Figure 6

Refractory periods of the atrium, A-V node, and rightbundle branch as a function of cycle length in one typicalpatient (patient 8).RBB =refractory period of the right bundle branch

represented by open triangles and connected with inter-rupted lines. AVFRP= A-V nodal functional refractoryperiod represented by open circles and connected with fulllines. AVERP-A-V nodal effective refractory period rep-

resented by open circles and connected with interruptedlines. AFRP =atrial functional refractory period repre-sented by closed circles and connected with full lines.AERP=atrial effective refractory period represented byclosed circles and connected with interrupted lines.


with an H,-H2 between 350 and 470 msec producedright bundle branch block pattern. At a cycle lengthof 580 msec, the A-V nodal FRP was 375 msec, andimpulses with an H1-H. interval between 375 and395 produced right bundle branch block. At a basiccycle length of 470 msec, the A-V nodal FRPexceeded the right bundle branch refractory periodand functional right bundle branch block was notnoted. At the longest cycle length (790 msec) theatrial FRP exceeded the A-V nodal ERP. Sincethese RP diverge at shorter cycle lengths, A-V nodalERP exceeded atrial FRP at these cycle lengths.

DiscussionEffect of Cycle Length on Refractory Periods

It has been demonstrated with microelectrodetechniques in isolated cardiac tissues that actionpotential durations and refractory periods of atrialmuscle, ventricular muscle, and His-Purkinje cellsdecrease with shortening of cycle length.' The A-Vnodal cell differs in that recovery of excitability isdelayed beyond complete repolarization. At higherdriving rates, this gap between complete repolariza-tion and recovery of excitability increases further.6Mendez et al. examined the effects of changes incycle length on the functional refractory periods oftissues in denervated canine hearts. They demon-strated that the functional refractory periods of theatria, ventricles, and A-V node were a curvilinearfunction of cycle length and shortened as cyclelengths decreased.2 Although our findings in manshowed similar changes, the changes in refractoryperiods produced by changes in cycle length couldnot be described in terms of a single mathematicalfunction. In this respect our results differ from thoseobtained in canine hearts. This difference canperhaps be explained by the fact that autonomicnervous systems were intact in our patients. Inaddition, the cycle length ranges we could studywere limited since heart rates could not be slowerthan spontaneous sinus rhythm, or faster than therate at which A-V nodal Wenckebach periods wereobserved. Atrial ERP and FRP had positive meanslopes when related to cycle length. The A-V nodalERP had a negative mean slope when related tocycle length. In the recordings for all except onepatient A-V nodal ERP increased when cycle lengthwas decreased. In contrast, the FRP of the A-Vnode had a positive mean slope, although there vasa wide scatter of individual patients (fig. 4).Refractory periods in the His-Purkinje systemshowed the greatest decrease as eyele lengthshortened.

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Relationship between Refractory Periodsof the Cardiac Tissues

The FRP of an excitable tissue at a given cyclelength is the shortest attainable time intervalbetween two impulses traversing that tissue, mea-

sured at a point distal to the stimulation site.2 TheERP of a tissue is the longest time interval betweentwo impulses where the second fails to traverse it. Ifthe FRP of the atrium is longer than the ERP of theA-V node, the A-V nodal ERP cannot be measured,

since the atrium limits A-V conduction. Therelationship between change in atrial FRP and A-Vnodal ERP in response to variation in cycle lengthshowed that the atrium might limit the determina-tion of A-V nodal ERP at long cycle lengths, butthis is less likely to occur at short cycle lengths (fig.6 and table 2). A similar relationship between theA-V nodal FRP and the RP of the His-Purkinjesystem is possible. In long cycle lengths, therefractory period of the right bundle branch isfrequently longer than the FRP of the A-V node.This allows a premature beat to be conducted withan 1-H2 interval shorter than the right bundlebranch refractory period, producing functionalright bundle branch block (aberrant conduction).At shorter cycle lengths the right bundle branchrefractory period and the A-V nodal FRP converge,

and aberrant conduction cannot occur. Aberrantconduction of a premature supraventricular beat isthus more likely during sinus bradycardia or whenpreceding R-R intervals are lengthened.Measurement of His-Purkinje system refractory

periods with the atrial extra stimulus method isdependent upon three factors: 1) the A-V nodalFRP, 2) cycle length, and 3) the RP of the His-Purkinje system. In this study, those patients inwhom determinations of His-Purkinje system re-

fractory period could be obtained tended to haveshorter A-V nodal FRP than those patients in whomHis-Purkinje system refractory period could not bemeasured. Most determinations of His-Purkinjesystem refractory periods were obtained at cyclelengths greater than 600 msec. In two patients (5and 14), both with sinus tachycardia, initialrefractory period measurements could be obtainedonly at cycle lengths less than 600 msec.

Moe et al. noted a similar relationship indenervated canine hearts.7 In his study, bundlebranch refractory periods exceeded A-V nodalrefractory periods at longer cycle lengths. Epi-nephrine reduced the refractory periods of the A-Vnode, His bundle, and bundle branches. However,the epinephrine effects were more pronounced in

the A-V node than in the bundle branches. Thismight explain why bundle branch refractoryperiods could be obtained at cycle lengths less than600 msec in the two patients with sinus tachycardiawho were probably not under basal conditionsduring the period of the study.

Conduction Time and Refractory PeriodsA-V nodal conduction time (A-H interval)

increases as cycle length shortens. This increase hasbeen attributed to the low amplitude of the A-Vnodal action potential, the low A-V nodal restingmembrane potential, and the decreased rate ofdepolarization of the A-V nodal cells in response toshortening of cycle length.' Merideth et al.6 haveshown in rabbit hearts that the frequency-relateddepression of A-V nodal conductivity is associatedwith both an increase in diastolic threshold anddelays between full repolarization and recovery ofexcitability. Van Capelle et al.,8 working with ratheart, suggested that A-V nodal conduction time(A-H) could determine A-V nodal refractoriness fora subsequent impulse. Our study suggests that A-Hinterval might be a partial determinant of A-Vnodal ERP. No such relationship was found for A-Hand A-V nodal FRP.

Experimental Limitations

Several limitations should be considered in theinterpretation of our results. First, most of thepatients had evidence of organic heart disease. It ispossible that cycle length-refractory period relation-ships might have been slightly different in a groupof patients without heart disease. However, findingsin our six normal patients were similar to thefindings in the 18 patients with heart disease.Second, since autonomic nervous system influenceswere intact, reflex responses to paced changes incycle length could have influenced our results.Third, the results of this study probably are notapplicable to changes in refractory periods inducedby spontaneous changes in heart rates, as occurringwith exercise or change in posture. Spontaneouschanges in rate are generally mediated by changesin sympathetic and/or parasympathetic tone, whichhave direct effects on conduction. Similarly, thechanges described in this study would not apply tocycle length changes induced by drugs with directeffects on the conduction system.

This study therefore describes changes in refrac-tory periods related to paced changes in cyclelength and are of value in understanding cardiacelectrophysiological responses in man. These results


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may be directly applicable to changes in rate notmediated by the autonomic nervous system, asoccur in some paroxysmal arrhythmias or in A-Vblock.

References1. HOFFMAN BC, CRANEFIELD PF: Electrophysiology of

the heart. New York, McCraw-Hill Book Company,1960

2. MENDEZ C, GAUHZIT CC, MOE GK: Influence of cyclelength upon refractory periods of auricles, ventriclesand A-V node in the dog. Am J Physiol 184: 287,1956

3. DHINGRA RC, ROSEN KM, RAMMTOOLA SH: Normalconduction intervals and responses in 61 patientsusing His bundle recording and atrial pacing. Chest64: 55, 1973

4. SCHERLAG BJ, LAU SH, HELFANT RM, STEIN E,BERKOWITZ WD, DAMATO AN: Catheter techniquefor recording His bundle activity in man. Circulation39: 13, 1969

5. WIT AL, WEISS MB, BERKOWITZ WD, ROSEN KM,STEINER C, DAMATO AN: Patterns of atrioventricularconduction in the human heart. Circ Res 27: 345,1970

6. MERIDETH J, MENDEZ C, MUELLER WJ, CORDON GK:Electrical excitability of atrioventricular nodal cells.Circ Res 23: 69, 1968

7. MOE GK, MENDEZ C, HAN J: Aberrant A-V impulsepropagation in the dog heart: A study of functionalbundle branch block. Circ Res 15: 261, 1955

8. VAN CAPELLE FJL, DUPERRON JC, DUPBER D:Atrioventricular conduction in isolated rat heart. AmJ Physiol 221: 284, 1971


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KENNETH M. ROSENPABLO DENES, DELON WU, RAMESH DHINGRA, RAYMOND J. PIETRAS and

The Effects of Cycle Length on Cardiac Refractory Periods in Man

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1974 American Heart Association, Inc. All rights reserved.

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