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Title Experimental Studies on Attitude of Dogs with RegeneratedLiver Against Hemorrhagic Shock
Author(s) TSUJI, MASAHIKO
Citation 日本外科宝函 (1966), 35(2): 268-292
Issue Date 1966-03-01
URL http://hdl.handle.net/2433/207294
Right
Type Departmental Bulletin Paper
Textversion publisher
Kyoto University
268 日本外科宝函第35巻第2号
Experimental Studies on Attitude of Dogs with Regenerated Liver Against Hemon・hagicShock
by
MASAHIKO TSUJI
2nd Department of山 rgeryKanazawa Univer,ity. Medicnl School
(Director: Prof. Dr. Tc1110 HoNJO)
Received for Publication Jul、, 31,1965
CONTENT
I. Introduction Method of Lamson
II. Materials and Metho::ls
1. Material>
2. Production of Hemorrhagic Shock
i. Wigge目・ Method( Western R田erv’e
Method)
11. Modified Method of L;inN•n 3. Examinations and Methods
i. Maximum Bleeding Volume
ii. Time-span to Maximum Bleeding
Volume, Spontaneous Returning Time
and Time-span to 15 and 30 per cent
Spontaneous Returning
iii. おurvivalTime
iv. Chang田 inPortal Pressure
v. Chang回 inHematocrit Ratio
vi. Histologi四 IStudies
III. l~ esults
I. Results in :¥nimalぉ with50 per cent Liver
Iミ田町tion
i. Change in Red Blood Cell Count
ii. Rate of Hepatic Regeneration
2. R田 ultsof Experiment5 with \へligger’お
Me出od
i. Maximum Bleeding Volume
ii. Survival Rate
3. lミ円ults of Experiments with Modified
1. Group of Blood Returning at the Time
of 15 per cent Spontaneous Returning
ii. Group of Blood Returning at the Time
of 30 per cent S伊 ntaneousReturning
a. Maximum Bl閉 dingVolume
h. Time-sp:in to M川 imumBl田ding
Volume
"・ Time-span to Spontaneou' Return-
in耳d. Time-span to 30 per cent Spont・
aneous Returning
じ討urvivalRate
[. Influence of、Sexon the Results
g. Relation to Temperature
I. Changes in Portal Pr田sure
'1. Changか inHematocrit Ratio
6. Histologiι叫 Findings
i. Before Withdrawal of Bl山xi
ii. At the Time of Spontaneous Returning
iii. At the Time of 30 per cent Sponta-
neous Returning
iv. At the Time of 70 per cent S伊ntane-
ous Returning
IV目 Disrn田ion
V. Summar、VI. References
INTRODUCTION
It is well known fact that the liver plays an』mportantrole against various surgical
intervention. Above all, significance of the liver in hemorrhagic shock includes numerous
problems attracting interests of surgeons in every respect.
Hepatic resection has been considered to be a principal treatment for surgical diseases
of the liver since early days, and many reports on this aspect can be seen28>川. As the
*’l'he gist of the p陀即日tp3per w:同 reported 日t5Jst Annual M何 tingof .fop.111e同じ 恥 1etyof the Disease,; of
D沼田tiveUrg:‘111'.
REGENERλTED LIVER AG.¥INST HEMORRHAGIC SHOCK 269
marvellous understanding and advancement of physiology23l31>, anatomy32> and hepatic
regeneration14l3Bl have come to be introduced to the operative techniques, together with
the advancement in anesthesiology, extensive hepatic resection is positively carried out today
not only for primary malignant neoplasms of the liver25l 35l m, but for metastatic carcinoma
of the liver as concomitant removal of the malignant involvement. Accordingly, cases of
hepatic resection are rapidly increasing in number at present, attracting attention of di-
nicians to pathophysiology in organism with regenerated liver.
Notwithstanding the residual liver parenchyma encounters serious disturbances in in-
trahepatic circulation, in liver function and in enzymatic system of the liver, showing
degeneration of liver cells after hepatic resection, the residual liver parenchyma well stands
against this aggression and comes to exceed preoperative weight several weeks after sur-
gery2i 1i 24J 2n川 36l. On the other hand, however, so-called liver death, as pointed out be
HYED26l, BOYCE and others8l, implies an extremely delicate aspect of the liver against
aggressions in some occasions. It is also well noticed that resistance against aggressions
is smaller in organisms with impaired liver12i 1 si.
Pathophysiology of the liver in hemorrhagic shock has been investigated by WrGGERS49l,
FrNE13l, SHORR42l and others from various aspects, and prevailing opinions attribute the
cause of experimental hemorrhagic irreversible shock to liver anoxia. As decribed in the
above, the residual liver parenchyma well stands against the temporary serious liver insuf-
ficiency following hepatic resection and regenerates remarkably to restore to normal liver
in its weight, size and histological findings. When an organism with thus regenerated
liver encounters hemorrhagic shock which leads to profound liver anoxia, it is an interest-
ing clinical problem to clarify whether this organism shows tolerance by the phenomenon
of familiarization to aggression, as pointed out by PAREIS and others37l, or it is less re-
sistant as organisms having the impaired liver.
In the present experiment, the attitude of regenerated liver against hemorrhagic shock
was studied from such a standpoint, in order to explore an aspect of pathophysiology of
regenerated liver.
II. MATERIALS AND METHODS
1. Materials Seventy-two adult mongrel healthy dogs of both sexes weighing from 7.5 to 13.0 kg
were used in the pr田 entexperiment after they were observed at shortest for 3 days feed-
ing with mixed food. Experimental animals were divided into control dogs and those
with regenerated liver.
i) First Group; Group of normal dogs: for control study.
ii) Second Group ; Group of dogs with regenerated liver.
Fifty per cent of the entire liver was first resected and the dogs were subjected to
experiment 2 months after surgery. Dogs were fixed in the spine position on the table
and the abdomen was opened with upper median incision under intravenous anesthesia with
25 mg/kg body weight of pentothal sodium. The liver hilus was adequately exposed.
Then, the entire left superior, and entire left inferior lobes of the liver were resected by
mass ligature, and partial resection of the quadrate lobe and middle lobe was additionally
270 日本外科宝函第35巻第2号
performed. After the resection of the liver, the abdomen was closed. The dogs were
subjected to observation for 2 months, and the animals looked healthy were used as those
with regenerated liver. Hepatic resection was carried out so that the weight of resected
liver might correspond to 50 per cent of the entire liver weight. The entire liver weight
was assumed to be 3.0 per cent of the body weight according to the result of KAMIMURA,
in our clinic.
2. Production of Hemorrahgic Shock
Both control and experimental dogs kept away from diet for about 1 to 2 hours on
the very day of the experiment. As shown in Fig. 1, the dogs were fixed in the spine
position and anesthetized with intravenous injection of 15 to 25 mg/kg body weight of
pentothal sodium. A polyethylene catheter of 3 mm in diameter was inserted into the
femoral artery, and 3 mg/kg body weight of heparin sodium was administered. A three-
way-cock was connected to irrigator and mercurial manometer for artificial bleeding, re-
turning of blood and determination of arterial pressure, and another three-way-cock was
used for returning of blood and other purposes. All the apparatus used in the experiment
were strictly sterilized and all the experimental procedures were carried out in aseptic
condition.
i) WIGGERS’Method (Western Reserve Method) 49>
Blood was rapidly withdrawn through the polyethylene catheter inserted into the
femoral artery. As shown in Fig. 2, when the average arterial pressure reached 50 mmHg,
arterial presaure was maintained in that level for 90 minutes. Then, blood was further
withdrawn and arterial pr白 sure was held in a level of 30 mmHg for 45 minutes, and
entire withdrawn blood was returned.
ii) Modified Method of LAMSON29>
From the catheter inserted into the femoral artery, blood was withdrawn into an
Fig. 1 Illu,tration .,f Experiment. l'<"it
T コ
+lE
2U
A叫
JVB
VB
γlム
丁68cm
CAP.巧Oinmflg
↑ U:i色dt。rLηtu.siof¥and Other
J、to卜1anorr r おuyposes
¥ t ¥ Cathett.< in民moralVein
REGENERATED LIVER AGAINST HEMORRHAGIC SHOCK
Fig. 2 Chang問。tArterial I》res.;ureand
Bleeding Volume in Hemorrhagic
Shock by Wiggers' Method
271
A寸前叫If'tuso .. (Mo内)
irrigator which was kept in the height of 68 cm
from the heart of the animal fixed in the spine
position. As shown in Fig. 3, by shifting the
irrigator up and down, arterial pressure was held
in a level of 50 mmHg, and the entire with-
drawn blood was returned after certain interval
of time.
↓?岬山notBl凹州陶叫M叫V。l叫帆)
J I-一一一一一一一十一一 ー ー一一1501 印•9v•okm比'"''' No叩 M>vUICTllι >Id;<
100
50
。
('"""'""
.4.r.叫 lp,.,,,時
"'"副
3. Examinations and Methods
In WIGGERS’method, maximum bleeding
volume and survival time were determined both
, 2 3 4 , 6 1 g q ·o~, in control and experimental animals, and in
LAMSON’s method, maximum bleeding volume,
time-span to maximum bleeding volume, spontaneous returning time and survival time
were determined. Portal pr回 sure and hematocrit ratio were determined to disclose an
aspect of intrahepatic circulation and hemodynamics, and changes in intrahepatic circula-
tion and liver cells were studied histologically.
i ) Maximum Bleeing Volume
When WIGGERS’method is used, the term of maximum bleeding volume represents
the volume of bl田 dingat a moment in which withdrawn blood volume required for the
production of shock state was the largest, while in modified LAMSON’s method it means
the volume of bleeding at a moment in which increment of bleeding ceas白・ Fluctuation
of bleeding volume was represented in a unit of 10 cc and determination was performed
every 10 minutes.
ii) Time-span to maximum bleeding volume, spontaneous returning time and time-
span to 15 and 30 per cent spontaneous returning.
As bleeding is commenced using modified method of LAMSON, volume of blood within
Fig. 3 Changes of Arterial Pressure and Bleeding Volume in Hemorrhagic
Shock b、ModifiedMethod of Latll><旧
. ..¥rterial Pr田sure(mmHg) j Proportion of Bleeding to Maximum Bleeding Volume (%)
S!ageojBI叫ng 且恥|胡叫~1<.iチ ミ同ιo\主i-vnl胡 eusBlo叫Jkιturi1
150 ct乱,.;thA山c.1¥I,I"'""山 h山内ιぺ15,X半円IB\wJ~clυγn
I 00
so .U'5l0門
。1
Bleedi『9 3 2 4 5 13 q 10 I I hvs. マ6
272 日本外科宝函第35巻第2号
the irrigator continues to increase, which ceases, however, after certain interval of time.
The interval of time between the commencement of bleeding and this moment is defined
as time-span to maximum bleeding volume. Volume of bleeding does not change for a while thereafter (this is called balanced stage), and it begins to decr回 seafter certain in-
terval of time. This moment is called spontaneous returning time. Blood within the ir-rigator continues to decrease thereafter, the moment, in which already returned blood
volume reaches 15 or 30 per cent of the maximum bleeding volume, is called time-span
to 15 or 30 per cent spontaneous returning, respectively.
Time-span to maximum bleeding volume corresponds to the time required for decreas-ing blood pressure to 50 mmHg, and spontaneous returning time corresponds to the moment in which the compensatory 回 pacityof organism comes to be unable to maintain blood
pressure of 50 mmHg. As mentioned in the below, time-span to 15 and 30 per cent spontaneous returning is considered to correspond to an adequate interval of time to produce
reversible and irreversible shock, respectively. In the present experiment, it was intended
to find out some differences between control and experimental dogs, from the difference of these intervals of time. Reading of these time was considerably difficult, and it was done by the help of movement of small air-bubble in the catheter placed in a horizontal
plane, which was watched for a while. During the experiment, obstruction was frequently observed due to blood clotting, but it was removed by additional administration of heparin, aspiration and/or pushing with syringe.
iii) Survival time
Interval of time between the commencement of bleeding and death was checked. When animals survived over 12 hours, observation was done thereafter every 1 hour, and in the survivals of more than 18 hours, it was pursued if the animals were alive or dead.
iv) Changes in portal pressure
Hemorrhagic shock was produced in 5 control and 5 experimental dogs using modified
method of Lamson. The entire blood within the irrigator was returned at 30 per cent spontaneous returning stage, and portal pressure was simultaneously determined. Portal pressure was determined through the catheter inserted into the portal vein from a branch of mesenteric vein by laparotomy prior to the production of shock state.
v) Changes in hematocrit ratio
Hemorrhagic shock was produced by modified method of Lamson in 6 control and
6 experimental dogs. Hematocrit ratio, was determined at the moments of maximum bleeding, spontaneous returning time, time of 30 per cent spontaneous returning and 90
minutes after returning of the entire withdrawn blood. Determination of hematocrit ratio
was done following the method of Wintrobe using blood taken from the femoral artery.
vi) Histological Studies
Histological study was carried out 1 control and 1 experimental dogs. The animals
were anesthetized as described in the above, and the abdomen was opened with upper median incision. Tissue section of the liver was taken from the marginal part of the
hepatic lobe. The sections were also taken from a dog subjected to the Lamson’s method
without blood return, at the time of spontaneous returning, time of 30 and 70 per cent spontaneous returni
REGENERATED LIVER主G主INSTHEMORRHAGIC SHOCK 273
immediately fixed in 10 per cent formalin, which were provided for production of paraffin
section. The microscopic sections were stained with eosin and hematoxylin.
III. RESULTS
1. Results in Animals with 50 per cent Liver Resection
i. Change in red blood cell count
As shown in Tab. 1, red blood cell count was 434×104土16×104,on the average,
1 week after hepatic resection, revealing a decrease of 15 per cent compared to preopera-
tive level of 514×104土33×104. Red blood cell count remained in a low level of 480
×104土21×104, even 4 weeks after surgery, which, however, roughly restored to pre-
operative level to become 514×lQ4士35×104,8 weeks after surgery.
ii. Rate of hepatic regeneration
As represented in Tab. 2, rate of hepatic regeneration was from 86 to 111 per cent,
97土8per cent on the average, of the preoperative entire liver weight, which corresponded
to 71 to 122 per cent, 94土16per cent on the average, of the resected liver weight, 2
months after hepatic resection.
2. Results of Experiments with WIGGERS’Method
Experiments of hemorrhagic shock following WIGGERS’method was carried out in
11 control and 9 experimental dogs, during the period from September to December in
1963, as shown in Tab. 3 and Tab. 4.
i. Maximum bleeding volume
As shown in Fig. 4, maximum bleeding volume in control dogs was from 38 to 53
αkg body weight, 46土3cc/kg body weight on the average, showing considerable in-
dividual difference. Maximum bleeding volume in experimental dogs was from 41 to 54
cc/kg body weight, 4 7土4cc/kg body weight. Although there was not a small individual
diference in both of these groups, a significant difference could not be found in these 2
groups.
ii. Survival rate
Twelve hour survival rate in control group was 6 111 (54 per cent), as shown in
Tab. 3, and 24 hour surv甘alrate was 2/11 (18 per cent), while 12 hour survival rate
in experimental group was 5. 9 (55 per cent), as shown in Tab. 4, and 24 hour survival
rate was 2/9 (22 per cent), revealing no significant difference in these 2 groups.
3. Results of Experiments with Modified Method of LAMSON
Tab. 1 Chan日りりfRed Blood (、ellCount after 50°0 Hepal町 tomy
I〕ogNo. Preope. ×J0・1
After 1 W 1 After :?W × 101 × JO•I
After -!¥!¥/ 1 After 6W I 入ft≪rfl¥¥'
x J04 I x J04 I x l別
41'..'.
1-12
458
HO
100
506
166
502
nUTA
nu只υ
F
ヘυP
ヘυ
508 つ-
pboo
-A
のム
oon白
510
546
468
182
564
126
438 5:; l
Mean 51」士33 ふ134士16 449士27
l忌6 」64
121
468
172 -186
526 557
第 2号第35巻日本外科宝函2n
Liver Post Mortem
Inererr g ! % %
126 ! 96 ! 93
94 86 71
157 11 1 目 122
92 : a9 I 19
146 103 i 106
四士24 I 97±8 1 9~~
Body Weight kg
9.0
1.~
9.0
7.5
8.0
8.0士0.5
Reop.
9.0
9.0
8.5
7.5
9.0
Dog Nり
qLPOno
--つん
0000
Results
after川目 Iafter叫
115 ・ 52 I Surviv吋 I 16.00
130 ' 46 I Survived I 14.00
120 . 50 1 11.20
130 ' -16 j St iv
130 口 I Su円 ived
1~5 j.j ~ 7.50
120 I 17 I Survived 110 38 9.40
1 IO 48 Survived
130 53 8.30
110 13 ' 11.40
1 Survived/Total
6/11 I 2/11
8.5土o.s1ι1ean
Hemorrhagic Sh配 kby Wiggeば MethodI仁川1tnil、)Tab. 3
Bod、Wtkg
Survived
16.00
13.00
Survived
Max. Bleeding Volume cc/kg Body Wt.
Arterial Pressure mm Hg
δ
0
0
0
0
0
5
0
5
5
0
9
8
1
9
0
a
8
a
8
8
9
1
1
Se,
♀
合
♀
合
合
合
♀
♀
合
会
♀
Dog No.
’in
J
E
J
7
’nud
ハUηJ417gnkuqu
m
j
7,【i
勺,ゥ,
7a
路
一’’An
H
V
《
HU
一孔
D
D
:判
7
4
山
比
一
白
・
1ill-
則一
R
E
m
d
d
)
i
d
l
吋
l,閉
山-
2
w
w
五
kvkmv託いい
ー一
L
何
mlblmふ
川
紅
川
jm一
加
白
出
l
h
h
出
e聞
n-
ub
-
ρ
、.3え圃
Ln
-
s-
pb
-
O幽
D
-
T叩-e
-
M
一μhE
げh
-K
-
バリE
C
-
ub
-
JAm
」6士3120士108.5土 0.5M"・"'
Tab. 4
Survived
I Survived
Survived/ fo旬l
も/9 ; 2/9
Tab. 2 Regeneratiりnof Liver 60 Da~» after 50°ムHepat怠ctomy
Liver at Operation, 1
Caleulaled I
Removed!Remnant I Total I Total ' Post Mortem , I I g I g ' g I g i
136 I 134 210 260 ,
132 138 270 ! 232
1 ~9 126 255 283
116 I 109 I 225 ! 201
138 132 270 I 278
130士6I 128士7 260土 15,251土24i
13.00
Max. Bleeding Volume cc/kg B,刈yWt.
イ
7
1
6
2
8
1
2
3
一
日
l
-」
5
1
4
5
4
一17士1
Arterial I'r白 suremm Hg
110
120
120
110
140
120
130
130
120
120士5
l弘川、\\ I
kg
9.0
9.5
I ;J
9.0
7,5
8.0
8.5
I ,;J
10.0
ト)u 入
一比一
13f平
合
平
早
合
一
Mean
I><山 ;-.J,’
i. Group of blood returning at the time
of 15 per cent spontaneous returning
Entire withdrawn blood was returned at
the time of 15 per cent spontaneous retruning
in 3 control and 3 experimental dogs. The ob-
tained results are summarized in Tab. 5.
Maximum bleeding volume was from 41
to 50 cc/kg body weight, 45土3cc/kg body
weight on the average, in control group, while
in experimental group it was from 42 to 49
cc/kg body weight, 46土3cc/kg body weight
on the average, showing no marked difference
between these 2 groups.
Spontaneous returning time in control group
was from 2 to 3 hours, 2 hours and 30 minutes
土20minutes on the average, and in experi-
mental group it was from 1 hour and 50 minutes
to 2 hours and 50 minutes, 2 hours and 20
minutes土20minutes on the average, also re-
vealing no significant difference between these
2 groups.
Twenty-four hour survival rate in control
group was 313 (100 per cent) and it was also 3/3 (100 per cent) in experimental group.
Thus, there was no significant difference in these 2 groups, all the animals in both groups
surv1vmg.
ii. Group of blood returning at the time of 30 per cent spontaneous returning
The results of blood returning at the time of 30 per cent spontaneous returning in
16 control and 14 experimental dogs are summarized in Tab. 6 and Tab. 7.
a. Maximum bleeding volume
As shown in Fig. 5, maximum bleeding
275 REGENERATED LIVER AGAINST HEMORRHAGIC SHOCK
Fig. 4 Maximum Bleeding Volume in Hernor-rhagic Shぽ kby Wiggers’Method
;弘
. 8
-・50・ 。
. . . 40 。
30-
ト受と Contrnls Do95 with
Rvieneraled Liver
group was from 34 to volume in control
: MI"<. Bleeding Volu Se ,Body Wt. Arterial Prt"'川 Ifぐ
ミ; kg mmHg i~:~::~~~王宮京 j Begummg
I 1.50 50
I 2.00 I 」l
1.20 41
I 140±20 I
Cases "i th Arterial Infusio日;1tthe Stageけ115% S1xmtaneous Blcx>d Return
削げげ
hD
Jm
ク
’HO
/
口υ
5
仰
M
「ー
ト
eOR
e
m
T
Tab. 5
1'1.esults
S11n・l¥Td
?ぢurv1v刊 l
Survived
3目 !O
し00
2.50
3.00
2.40
2.00
2.30士20
130
130
110
120土10110.0士!.~
1~.o
9.5
7.5
♀
♀
合
14qopo
q吋υ
内べ
υηtυ
J
一=ι==)
Sm、l、r!
Sur、l、打l
Survived
3.30士30I
z.3o I 3.40 I .50 1 '.C.10
2.50 I 3.20
乙20士20 1・ 3.10±20 I
15士3
』6土3
QJ
内
/
】
弓
j
tL‘
a4144A
120士10 I 1.3山
9.0
8.5
10.0
9.0士0.5
平
合
合
Mean
II
42
43
Mean
日む〉同
J
-v心亡にむ己UM叫Uザ一
月一
τιL同cc
276 日本外科宝函第35巻第2号
52 cc 1kg body weight, 44土4じck広 body weight on the average, and in experimental
group it was from 36 to 53 cc/kg body weight, 45土4cc/kg body weight on the average,
showing no marked difference in these 2 groups.
b. Time-span to maximum bleeding volume
人R shown in Fig. 6, time-span to maximum bleeding volume in control group was
from 50 minutes to 2 hours and 50 minutes, 1 hour and 40 minutes士 20minutes on
the average, while in experimental group it was from 1 hour to 2 hours and 50 minutes,
1 hour and 50 minutes士 30minutes on the average. Although the results of the 2
groups spread considerably in a wide range, there was no significant difference between
these 2 groups.
c. Time-span to spontaneous returning
As shown in Fig. 6, time-span to spontaneous returning in control group was from
1 hour and 40 minutes to 4 hours and 10 minutes, 2 hours and 40 minutes土 30minutes
on the average, and in experimental group it was from 1 hour and 30 minutes to 3 hours
and 50 minutes, 2 hours and 50 minutes土 40minutes on the average. Although the
results of the 2 groups were scattered in a wide range, there could not be observed any
significant difference in these 2 groups.
d. Time-span to 30 per cent spontaneous returning
As shown in Fig. 6, time-span to 30 per cent spontaneous returning in control group
was from 3 hours to 6 hours and 40 minutes, 4 hours and 50 minutes土 50minutes
on the average, and in experimental group it was from 3 hours and 30 minutes to 7
Tab. 6 t・,トが withArterial lnfu剖onat the St.1gじり[30°占 s,”川t.tlll"""Bl印JdReturn (心mtrりlsI
1 ' • ;'vi.". Bleedin Volume. Time to Spont. Iミ田ultsDog i¥i,,_恥 BodyWt .. .¥rter凶 Pressure ~一一- Bl()(ld Retmn 一一 ー
同 J mmHg Time_ to l cc/ki; , Beginn・ 30% after 12 h見 lafter 24 hrs. 'I : h目 mt_i:!S・ JB《:idyWt. mg !
11 合 8.5 I 140 『 2.10 .17 3.20 5.50 臼rvived 17.00
16 ♀ 8.5 125 : 1.40 43 2.50 l.40 I l.40
17 cs 10.0 115 2.50 13 』10 6.40 Survived I LOO
18 合 8.5 135 1.20 -15 二JO 3.:20 Survived
JI 合 10.0 120 1.30 39 二.1υ3AO 日.20
35 ♀ 9.0 115 : 1.50 17 '.2.40 5.10 Survived 13.00
37 cs 8.5 120 1.40 50 3.00 l. l 0 10.00
38 CS 10.5 140 , 1.20 , 42 '.2.50 5.50 j Survived Died
5:2 ♀ 9.0 120 .50 ' 36 1.40 3.00 ! 9.20
53 合 8.0 I ~O 1.20 34 1.50 3.30 8.40
ω ♀ 8.0 125 1.30 43 : l.50 3.20 1.50
56 ~ 8.5 ' 115 1.40 13 i 2.20 5.00 J0.30
71 ♀ 7.0 130 1.50 5'.2 '.2.50 5.10 11.50
72 合 9.0 125 :!.'.20 ll 3.50 6.20 ' Sm、l、叩l Died
71 ♀ Li 115 '.2.20 16 3.JO G.00 9.40 1 ー
76 ♀ 8.5 110 I.HI 47 2.30 ・l.30 出 r、i、ed 13.00
i Survived/Total Me-dn '8.5士1.01 125士10 l.40±20 4.1士4 '.2.IO土304.50土日一 一
7/16 0/16
l¥EGE0:EI<.¥TED LIVEI¥. .¥CAINST HEMOI<RHλ(;IC SHOCJ¥ ハ門戸噌
ιJ II
Tab. 7 C山"' with Arterial Infusion at the Stage of 30% Spontaneous Blood l~eturn
1Dυ宮、"1th Regenerated Liver J
Dog No.I 決\
I iMax. Ble出 nf!Volurn~寸1rne to Spont. Bod、Wt.主rkri:ilPr白 sureIζBlood Return
kg mm Hg 寸而子下了一石7雇--Be;日irn;-6 300;
I hrs. rnins. Bodx Wt. 111にafter 12 h円.I after 2-1 hrs
23 050nωに
4
0
5
5
0
R
U
5
5
0
D
0
8
9
9
m
8
8
7
7
日
8
7
7
9
8
一
士一戸、υ
一。。
♀
8
6
8♀
♀
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♀
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♀
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目
125士5
2.1
25
135
140
125
115
130
115
110
110
26
46
日2
っjv《
hυ
勺
dn4dFhJPO
日νιv戸
huo白且
υnD
125
120
120
125
13云
120
Mean
Fig. 5 Maximum Bleeding Volume in Hemor-
rhagic Shock by Modified Method of Lamson
百60
/〕ー. .
50- 。。
~~o 。。 ,, 40 。 . . 。 . 。30
|震 Controls Do_9S附hRe~enrnited Liver
Results
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3.50 6.40 メ11r、I、肝I I Died
::LUO L己り 10.50
3.30 1 6.00 I Survived i 14.00
2.50 :'i.10 9.40
:uo 7.10 ! S11r、1、ed 17.00
2.00 : ;;.10 ' 11.10
3.00 ! 6却| 出川附l ' 15.00
1.50 3.30 i 8.50
z.3o s.oo I 11.20
2.00 ' l.10 i 川、i山 l 13.00
l目30 3.40 i 8.30
3.40 : 6.50 I Sm、l、叶 Died
'.C.50 l.10 9.40
2.10 51 2.20 i :i.50 I Survived 13.00
! 吋llf¥"日目 1rrりt日l2.50士105.30士60:
7/1・1 0/14
1.50±30 ' t:)士i
Fig. 6 Time to吋t1gP>of Balanced, Begmn-
ing and 30% Spontaneous Blc~d Return
-Controls -Dけ日、 withRegenerated Liw1
「lrl . 可 . 。
I c 6
()c 5
ハ~ CJ . 4
I 、一、乙
3 822 ~~・
r_, 《}
§;,A~ 2 か。 It . 。
L Balanced Be~inn•nq •t 30メネnl.5!oodR<totn 5f'"*・ Dlood ~ti; m
278 日本外科宝函可'n5~ ;~'~2 号
hours and 10 minutes, 5 hours and 30 minutes土 60minutes on the average, revealing
a slight prolongation in this group. The results in both groups widely spr田 ding,it was
difficult to notice recognizable marked difference between these 2 groups.
e. Survival rate
Twelve hour survival rate in control group was 7 /16 (44 per cent) and 24 hour
survival rate 0/16 (0 per cent), and in experimental group the former was 7 /14 (50 per
cent) and the latter also 0/14 (0 per cent). All the animals died until 24 hours after
surgery in both groups and there was no significant difference in these 2 groups.
f. Influence of sex on the results
Since the results of both control and experimental group were scattered in a wide
range in the experiment following the modified method of LAMSON, some possibility of
influence of sex on the results was presumed and analysis on this point was attempted.
Concerning maximum bleeding volume, as shown in Fig. 7, average value of male
dogs in control group was 43土2cc kg body weight and that of female dogs in the same
group was 45土2cc/kg body weight, while in experimental group average value of male
dogs was 46土4cc/kg body weight and that of female dogs in the latter group was
44土3cc k広・ Thus, even in analysis based on sexes, significant difference could not be
found between these 2εroups.
A只日hownin Fig. 8, spontaneous returning time of male dogs in control group was
2 hours and 50 minutes土 30minutes, on the average, and that of female dogs in the
Fig. 7 Relaliorship betwεen Maximum Bleed-in日 Volumeand Sex in Hemorrhagic討hocl、ll¥・ Modified Method of Lamson
c<y;匂
0 -Co叶川Is• -Do'S wolh "'•qenuatcd L,叫す
. 。. 50 0 • 0 g・
O e 0 G
ぁ. 8しi I. •_) .
40 0 • . ・ 0つ
30
均7 Male Femalε
Fig. 8 Relβtionship between Sex and Period りfTime tけ吋tage'of Balanced, Beginning and 30% Spontaneous Blood Retur 日
. " -門•I• "o - ιOTih•IS •o -fem4Jc • ・Do~S w・耐 R勾enera匝Aじ"'
hTS
~
マ. .
" . A ‘
6
A oo• 5 t:. &
g •
4 A " . 企 I. A .. A f A 。
3 A A p!年・ 。..
~:· ~:よ2 . 、ゑ
に; Balanced Bc,inn,崎。7 JO戸怜ontBI叫 h加、 加!Bioodl¥t!tm
REGENER..¥ TED LIVER .¥CλINST HEMOl<IミH.¥Clt、子、1-1<凡h: :C79
same group was 2 hours and 30 minutes土 30minutes, on the average, while that of
male dogs in experimental group was 2 hours and 50 minutes土 30minutes, on the
average, and that of female dogs of the latter group was 2 hours and 40 minutes土 40
minutes, on the average, showing no obvious difference between both sexes and both
groups.
g. Relation to temperature
During the course of experiments following the modified method of LAMSON, some
correlation between the results and temperature was infered and it was considered that
this interference of temperature might be a cause of so much scattered results of experi-
ments. Therefore, from a presumption that some significant difference would be sought
between control and experimental groups, when the results of experiment are analysed
excluding the interference of temperature, experimental results were analysed o.n this pre-
sumption. Namely, experiments following modified method of LAMSON carried out during
the period of 1 year from September 15, 1963 to September 14, 1964 were divided into
4 groups; experiments done from September 15 to December 14, (Dog No. 1-9, 70-
89) in autumn, experiments done from December 15 to March 14, (Dog No. 10-29)
in winter, experiments done from March 15 to June 1 I, (Dog No. 30 49) in spring
and experiments done from June 15 to September 14, (Dog No. 50 69) in summer.
~~( l'I 》11,
15. Dec ~l J. Mar
13. M肌
~1 I. Jun.
15. Jun. ~I!.たpt.
).). Sept. ~H. D民\
Mean
Tab. 9
丸吋"'川 、
15. I>町
13.
~l .J. I、'i.1r
~l -1. Jun.
l九.Jun. ~14. s叩t.
Tab. 8 Relalionship hetween Hemorrhagic Shock and Temperature I Contrけkl
Dogs Mean ' Time to Max. Bleeding I Maxy ~leed- !Time to Spcnt. J Surv1川
T、冶e町叩I w hrs. mins. Body t. hrs. mins. after 12 hrs.
5.0 2.30士30 4.1士3 3.15士30 3/ーl
I 13.5 1.50士JO 4~土4 :CAO土20 21」ホ
4 23.・1 1.20士20 38士3 1.55土 10 0/4
4 12.l 2.00士20 ー!?土2 3.10士30 2/4
19 i 1 l.5 1.40土20 ーI~ 土4 2.40士30 7/16
Relationship between Hemorrhagic Shock and Temperature I D1》g'、、ithH.egenerated Liver)
Nト弔問iB~:叩午' i~l時王子山;;rs .4 5.0 I 2.JO土5 48土3 :i.:.'0士三日 21』
6 15.5 1.50士30 16士2 2.50士30 2/3'‘
2;).-1 1.20士10 39±2 2.00士20 1/4
15. Sept. っ 12.1 2.00±20 ' 48土3 I 3.20±20 1 213 ~l .J. Dec. , v
Menn 17 11.5 J元副 一一 .J:)士l下2:;-±3;下一日7* Other 3 dogs out of 7 \\’ere 'ubjected Iけ"'"' ''"・ith arterial infusion at the stage of 15°ふ只戸川t印刷出 bl口氏lreturn in hemorrhagic shock lηmodified method of Lam田 n.
280 日本外科宝函第35巻第2号
Based on this classification, maximum bleeding volume, time-span to maximum bleeding,
time-span to spontaneous returning, time-span to 30 per cent spontaneous returning and 12
hour survival rate were studied, as represented in Tab. 8 and Tab. 9. Average tempera-
ture at noon was 12.1℃ in autumn, 5.0°C in winter, 15.5°C in spring and 25.4°C in
summεr, year round average temperature being 14.5 'C.
Concerning maximum bleeding volume, as shown in Fig. 9, the values were lower
in summer to be 38土3cc/kg body weight in control group on the average and 39土2
cc/kg body weight in experimental group on the average, being lower than year round
average value of 44士4cc/ kg body weight in control group and 45土4cc/kg body weight
in experimental group. The largest value in this season was close to the smallest value
in other three seasons. However, significant difference could not be observed between
these 2 groups, even when the influence of seasons was taken into consideration.
Spontaneous returning time and time-span to 30 per cent spontaneous returning were
also obviously shorter in summer in both groups compared with those in other three seasons.
Twelve hour survival rate in control group was 0/4 (0 per cent) in summer, whereas
in other three seasons it was 7 /12 (58 per cent), and in experimental group it was 1/4
(25 per cent) in summer, whereas it was 6/10 (60 per cent) in other three seasons,
both showin広 obviouslylower value in summer. However, there was no significant differ-
ence between control and experimentalεroups, even though the influence of seasons was
taken into consideration.
As obvious from these findin停, the results were worse in summer. Hereupon, the
Fig. 9 Relationship hetween Temperature an<l Maximum Bleeding Volume
0 -(o.,,trols ・- Do9.s w;Jh Re'eneu1te.d Live<
c%9
. 0 •
50 . . ~ αっ.. 8 。
0・s• α. 40 . 。 .
0・。30
援らo~ 1 5.s•c 2 5.4(: I 2. 1 •c.
15.Deε 15.門ar. 15.Jun. l'i.S.pt 14.1'』 14.J,υn. 14.Sul 14.匝£,
Fig. 10 Relatiけnshiphetween Temperature and Time t日目tage"of Balanced, Beginning and 30?; Spontaneous Blond Return
hrs '7
6
。"o Co• 十•ols..・- bo9s w川 Re9enet首吋 L,叫V
B・-l!alancod ’
LI A -Be,i>nlng・TSpontaneous Blood ~d'rn 口• 3o;4Sp馴 1ane。usBlood l¥e1川 7、
. 0・ . . ロ. ロ. ロ
ロ。ロ ロ
5 句。.
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ロ
4 A ロ .
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d込
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' • 0
~~t A
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6• ~ J. 0 0 ・。a• ・. .
5 0・ι I 5. 5'仁 2. 5. 4・c I 2 I・ι15 Dec 15.門" 15 J;n 15.古"ff
. . .
l一~~ζa剖/'" 14 M"、 14 Jυn /45の1 / 4.Dec
281
results obtained during summer season was excluded and those of blood returning
time of 15 and 30 per cent spontaneous returning in control and experimental groups
were compared with each other. Maximum bleeding volume in control group was 45土
4 cc/kg body weight on the average and 47土3cc 'kg body weight in experimetal group,
revealing no marked difference. Time-span to maximum bleeding volume was 1 hour
and 50 minutes士 20minutes on the average in control group, while it was 2 hours
士 20minutes on the average in experinental group, and no significant difference could
be observed. Spontaneous returning time was 2 hours and 50 minutes士 20minutes
and 3 hours土 30minutes in experimental group, also revealing no marked difference.
Time-span to 30 per cent spontaneous returning was 5 hours and 20 minutes土 40
minutes in control group and 6 hours士 40minutes in experimental group, showing no
significant difference between 2 groups.
Twelve hour survival rate was 7 /12 (58 per cent) in control group and 6/10 (60
per cent) in experimental group, similarly showing no significant difference.
From these findings, it is assumed that there existed no significant difference between
control group and experimental group, even when the influence of the seasen was taken
into consideration.
4. Chan広esin Portal Pressure
Hemorrhagic shock was produced following the modified method of LAMSON in 5
control dogs and 5 experimental dogs. Blood was returned at the time of 30 per cent
spontaneous returning, and changes in portal pressure were simultaneously studied.
As represented in Tab. 10, Tab. 11 and Fig. 11, portal pressure before withdrawal
of blood was from 111 mmH20 to 138 mmH20, 125土9mmH20 on the average, in
control group, while it was from 135 mmH20 to 154 mmH20, 146 mmH20 on the
average, in experimental group, obviously showing higher level in the latter. As the
at the
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Char取引けfpりrtalPre>>Ur~ in Hemorrhagic Shock h, Modified Method of Lamson
After Total Arterial Infusion hrs.
Tab. IO
3
100
110
125
60
106
2
J
一こ」H
==’}
』
rw-己斗℃おEbCむ註むと
戸一--F王子Z(』
第 2号
withdrawal of blood was started, portal pr田 surebegan to decrease in parallel with rapid
fall in arterial pressure in both groups, although the degree of decrease was smaller in
portal pressure. Changes in portal pr白 surewere ever resembling to each other in control
group and experimental group, which reached the lowest level at spontaneous returning
time, corresponding to 60 per cent and 58 per cent in control group and experimental
group, respectively. Portal pressure turned to increase in most cases at the time of 30 per cent spontaneous retruning. By the blood returning at 30 per cent spontaneous return-ing, arterial pressure mostly restored to 90 per cent of the level before withdrawal of
第35巻日本外科宝函内8~
Changes of Arterial Pressure in Cases with Meosurement of Porto! Pressure in Hemorrhagic Shock hv Modified Method of Lamson
同
一
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Tab. 11
wyiJ
M
m
匂
い入、Nuhk
円
仁D
N
Tinw to cc/kg Be.ginn-, |官、 mins.ぬ刈、Wt. mg
51 ♀ 8.5 i .50 ' 39 1.40
I s4 ♀ 8.5 [ 1.20 ~ 4 1 : ~ .00 55 ' 合 9.0I 1. 10 46 3.00
! 57 c JO.O I 1.00 36 ~. 10 I ss ♀ 9.0 i l.30 39 i 2.10
I Mean 1.20士20 40土3 2.20士303.20士20'
61 l♀ 9.0 J..10 41 1.50 ' 3.40
64 ♀ 7.5 .50 : 38 2.20 4.00
65 ' ♀ 8.5 ' J.30 4 l 2.00 ~ 5.10
68 合 9.0 1.50 i 37 2.40 1.-10
I 69 I c 9.0 ! 1.00 i 46 I 2.20 ! 3.00 i
Mean ; 1.20土20;40士3:-2.1己士20i1.10士一
30°;;
J
一±」】こ=υ
LL
=」一Wu--7』む
pzxhuγ
-
戸一=5JU4
=ニ
Fig. 11 Changes of Portal Pres.~ure in Hemorrhagic Shock b,-Modified Method of L1m田口
守Y凶桁色釧e(mm帥
200 I 0・ιorilr。ls.‘Do,$ ....,;fh句馴U&tGdliver
15" 0
100
h~. tr t ヲ
30メ恥it81~~ Re:tuv~ 21,;d Tot.ill Attt11'al lntusicm
相t.Bloo:I~伽n+
~.Bl凶l1j
So
。跡,yeJ1~n9
blood, whereas portal pressure showed marked increase in both groups, exceeding the
level before withdrawal of blood. Rate of increase in portal pr回 sureafter returning of
blood in experimental group was slightly higher to 120 per cent compared with the average
value of 110 per cent in control group. Portal pressure behaved in a similar tendency
in both groups in parallel with a decrease in arterial pressure thereafter, although the
former was maintained in relatively high level.
5. Changes in Hematocrit Ratio
Hematocrit ratio was determined in 6 control and 6 experimental dogs of blood re-
turning at 30 per cent spontaneous returning in modified method of LAMSON. As shown
in Tab. 12 and Fig. 12, hematocrit ratio before withdrawal of blood in control group
was from 38 to 50 per cent, 45土4per cent on the average, and it was from 36 to 51
per cent, 43士4per cent on the average, in experimental group. The value decreased
gradually in both groups in parallel with blood withdrawal, which remained in lower level
at balanced stage and stage of spontaneous returning. Hematocrit ratio began to increase
again towards the time of 30 per cent spontane-
ous returning. It increased on after returning
of blood, in most cases showing a tendency of
blood condensation exceeding the level before
withdrawal of blood, 4 hours and 30 minutes
after retunning of blood.
6. Histological Findings
As shown in Tab. 13, hemorrhagic shock
was produced by modified method of LAMSON
without returning of blood in 1 control and 1
experimental dogs. Obtained histological find-
283 RE<;J.:NlミRλTEDLIVER.\心λINSTHEMOR!くHAGICSHOCK
Fig. 12 Changes of HematocritRatio in He-morrhagic日hockJ,,・ Modified Metho【Iof
so
40
- ,,,
30
制働時 r.州抑凶1oodR•'"""'"'""''・·~' L聞かg・・n
h伊陣副司 h 脚内
Changes of Hematocrit Ratio With the Lapse of Time in Hemorrhagic Shock by Modified Method of Lamson
Tab. 12
After Total Arterial lnfusio日
・l.5 hrs 3 hrs.
Qd
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37 39
37 38
36 37
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13 -15
3.1 35
33 : 36
39 i 38
40 ' 40
36 36
」3 43
11 41
1.5 hrs
Changes at the Stage of
Spont. Blood Return
Beginning 30?占
3.1
36
32
40
43
36
ηノム只u1lnoquFD
つοqJ44hqosqqo
6
7
3
2
4
0
一4
9
2
9
5
5
3
3
3
4
4
4
一3
3
4
3
4
3
No.
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日UGdaunuFb44APOFbqυnU14
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4
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4
4
4
5
4
80
90
75
110
80
80
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会
合
♀
一
平
合
合
♀
早
合
Dog
Bleeding
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3
5
7
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-
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284 日本外科宝函第35巻第2号
Tab. 13 Case> with Histological Observation of Liver in Hemorrhagic Shock by Modified Method of Lamson
[ Max.印刷mgi Time t口 SpantaneousBlood Return I Dog, ,HけdyWt.1.'..¥rterial I , from the Time of Bl剖 inghrs. mins・lSurri刈
1 Sex I ,ressure :-- 一一一f一 一一一- ! 一一一一一←一一一No. 1 ほ :mmH日 :Time判cc/ほ iBe~inn- i 30°' I 50% 70% I 10眠 Time
I :hrs. mins.!BodyWt.; mg 1 '0 ! I
c~~t~ol ___ __I _:z_:亘互戸竺i~ .00 1_ :~_vvi. , ・_fk_ i _~~~ '_ -豆I~玉江更hぷh~~~:rner- i 4 1合 9.0I 125 i 1.50 i 46 i 2.50 ! ・l.40 i 6AO I 7.40 ! 9.00 : 9.20
ings are summarized as described in the below.
i. Before withdrawal of blood (Fig. 13, 14).
Slight cell infiltration in Glisson’s sheath and irregularity of acinal structure could be
observed here and there more frequently in regenerated liver than in control liver. No
characteristic abnormality could be otherwise observed.
ii. At the time of spontaneous returning (Fig. 15, 16).
Congestion around the central veins and central sinusoids could be observed in both
grou伊 withaccompanying hemosiderin granules in Kupffer cells and vacuole degeneration
in some central liver cells. In reεenerated liver, considerable infiltration of neutrophiles
was observed.
iii. At the time of 30 per cent spontaneous returning (Fig. 17, 18).
The changes differed little essentially from those at the time of spontaneous return-
ing, although they were slightly accentuated.
iv. At the time of 70 per cent spontaneous returning (Fig. 19, 20).
In both groups, atrophy of liver cells in the central area of the hepatic lobules was
marked, and in some places destruction of small number of liver cells and neutrophile
infiltration were observed. In the peripheral ar回 ofthe hepatic lobules, hemorrhage was
observed within Glisson’s sheath frequently, with neutrophile infiltration and liver cell
destruction around.
In general, regenerated liver sometimes showed considerably serious congestion and
infiltration of neutrophiles and small round cells when compared with control liver. How・
ever, degeneration and atrophy of liver cells were a little more slight in regenerated liver
than in control liver.
IV. DISCUSSION
Concerning pathophysiology of the liver in hemorrhagic shock, numerous studies have
been reported and the important role of the liver in such condition has been pointed out.
In hemorrhagic shock, intrahepatic blood flow decreases remarkab)y22>, and the liver, which
owes 80 per cent of its blood flow to the portal vein, encounters readily serious anoxia,
partly due to remarkable decrease in oxygen content in portal blood'人 Glycogenis released
from the liver in early stage41>, and with a progressive decrease in oxygen consumption
in the liver, glycogen content in the liver prominently decr白 sesaccompanied by marked
decrease in high-energy phosphate of the liver30H0>, disturbance of enzymes and co・enzymes
1ll45>, decrease in production of albumin10> prothrombin11> and fibrinogen18>20, release of
REGENERATED LIVERλGAINST HEMORRJ-1λGIC SHOCK 285
kalium41) ann increase in amino-acid content in blood33l. It is widely known that this
series of these phenomenon progresses closely in parallel with the degree of liver failure
due to anoxia. SHORR42> pointed out that VDM is produced in the anoxic liver, and
increase in this substance is a cause of irreversible shock. FJNE13> emphasized, in this
respect, proliferation of intrahepalic anaerobic bacteria四 usedby liver anoxia and toxin
produced by this bacteria. CoHN9> increased remarkably survival rate of shock by in-
creasing arterial inflow to the liver, in his experiment using liver perfusion. From these
observations, it is assumed that the liver is not only so much susceptible to anoxia in
hemorrhagic shock, but playing decisive role in the development of irreversible shock.
Now-a-days, liver resection is considered to be a principal therapeutic maneuver for
surgical diseases of the liver, and it is widely carried out. Accordingly, the patients haト
ing regenerated liver are largely increasing in number, and it is necessarily considered that
oc白 sion,in which such patients undergo surgical intervention for the second time, is ever
increasing. It is not only of pathological but of clinical importance to investigate whether
or not the regenerated liver, which is not less than normal liver in its weight and size,
shows characteristic response to the large alterations caused by surgery with or without
some resistance in such occasions, when it is considered that the liver plays an important
role, as mentioned in the above, against aggressions. From this point of view, experi同
mental regenerative liver was produced in dogs and its response to hemorrhagic shock,
which is assumed to influence the liver so largely, was investigaled.
According to the reports of F1scHBACK14>, MANN7J, Grindley et BOLLMAN and others,
weight of the residual liver parenchyma restor田 topreoperative weight 4 to 6 weeks after
liver resection of 70 per cent of the entire liver weight. Fisher15> also observed the
similar results of hepatic regeneration 1 month after hepatic resection of 43 per cent of
the entire liver weight. In recent years, significance of;portal blood16>, hepatic blood
flow15> and humoral factor3> has been gradually clarified. Considering these points, liver
resection was carried out in the present experiment to the extent of 50 per cent of the
entire liver weight, which scarcely causes stricture of the portal vein and is carried out
by simple procedures with expectance of getting sufficient amount of liver regeneration.
Experiment of hemorrhagic shock was performed 2 month after hepatic resection, at which
period influence of hepatic resection itself回 nbe made negligible as possible. At this
period, the residual liver parenchyma showed 94 per cent of regeneration rate and decrease
in red blood cell count observed shortly after liver resection already restored to preopera-
tive level. Accordingly, it was assumed that volume of hepatic resection and interval of
time between the resection and production of hemorrhagic shock was approximately adequate
for the purpose of the pr白 entexperiment.
Many methods have been reported on the production of hemorrhagic shock. Among
these, WIGGERS reported that normovolemic shock state can be produced by inducing
hypostatic condition in two phases and by returning the entire withdrawn blood after
maintaining blood pr白;sure in a low level for certain period of time. By this method,
however, it is not always successful to produce irreversible shock and WIGGERS reported
himself that the rate was 82 per cent. In the present experiment also, 24 hour survival
rate in control group showed approximately similar result of 2/11 (19 per cent). On
286 日本外科宝函第35巻第2号
the other hand, L主MSONdevised to produce hemorrhagic shock using a bottle for blood
withdrawal, in which blood pressure can be held in any level of hypotension. Although duration of time of hypotensive state differs considerably depending 11pon individuality by
this method of hemorrhagic shock, withdrawn blood in the bottle begins to return to the
organism spontaneously as the compensatory capacity of animals is exhausted out after
certain interval of time. Using this method, FINE observed that irreversible shock αn be produced if all the remaining blood within the bottle is returned to the body at the
moment when the volume of spontaneous ret町 nr回品目 30to 40 per cent of the max-imum bleeding volume. When this method was employed in the pr白 entexperiment, all
the control animals survived when the blood in the bottle was returned at 15 per cent spontaneous returning, and all the animals died when the blood in the bottle was returned
at 30 per cent spontaneous returning. Hence, it was assumed that this method was the
most suited to the aim of the present experiment, since by this method reversible and ir-reversible shock can be produced ad libitu111 and observation can be done preciously during the experiment.
It was pointed out by ALLEN1l, BERGMANNり andothers that shock is closely related
to temperature and weather. BLALOCK的 observedprolongation of shock state in chilly condition, and REMINGTON39' reported that for the production of the identical degree of
shock state, bleeding volume should be increased in winter. In the present experiment, results obtained during summer showed less maximum bleeding volume, shortening of
spontaneous returning time and decrease in survival rate in control and experimental groups compared with those obtained in other three seasons, obviously revealing decrease in shock
resistance. It is assumed that this should be carefully taken into account at the compari-
son of the experimental results. In this respect, experiment employing VVIGGERs’method was carried out during the period from September to December, in which temperatぽe
and weather is considered to have little influence on the experimental results, and analy-
sis of the experimental results by modified method of LAMSON was done with this con-
sideration.
In the results of experiment of hemorrhagic shock by WIGGERS’method, maximum
bleeding volume in control dogs was 46土3cc/kg body weight on the average, and that of experimental dogs was in the similar level to be 4 7土4cc/kg body weight on the
average. Twelve hour survival rate in control group was 6/11 (54 per cent), and it
was 5/9 (56 per cent) in experimental group. Twenty-four hour survival rates were
2/11 (18 per cent) and 2/9 (22 per cent), respectively in control group and experimental group, also showing no marked difference from each other. Principal aim of Wiggers’ method consists in producing hemorrhagic shock of identical condition by maintaining cer-
tain hypotensive state for certain length of time taking arterial pressure as an indiαtor. It is considered that there exist some occasions in which the state of shock still remains
in a reversible phase under such conditions without being driven to irreversible phase, partly owing to individual difference in compensatory capacity. In fact, in the pr僻 nt
experiment, approximately 20 per cent of the animals still survived 24 hours after produじ’
tion of shock state in control group, despite, on the other hand, animals of as many as
50 per cent died 12 hours after production of shock state. Accordingly, as was pointed
REGENERλTED LIVER ,¥G.-¥Iλ’ST HEMORRf-1.¥GIC SHOCK 287
out by WIGGERS’himself, influences of individuality cannot be neglected. Although it
was difficult to find difference to be mentioned in the experimental results between control
group and experimental group, as described in the above, conclusion as to the superiority
or inferiority of experimental animals cannot be readily drawn.
On the other hand, in the results of experiment by modified method of Lamson,
significant difference could not be observed between control group and experimental group
in maximum bleeding volume, spontaneous returning time and time-span to 15 per cent
spontaneous return, when the blood within the bottle was returned at the time of 15 per
cent spontaneous return. Significant difference could not be observed also in 24 hour
survival rate and the animals of both groups invariably survived. This finding is in-
terpreted that the animals preserve the capacity to restore around the time of 15 per cent
spontaneous return, even if compensatory mechanism of circulatory system is disturbed by
continuation of hypotensive state caused by withdrawal of blood. It is assumed that, in
this respect, both control and experimental animals have similar response. When the blood
within the bottle was returned at the time of 30 per cent spontaneous return, maximum
bleeding volume in control group was 44土4cc/kg body weight, and it was 45土4cc/kg
body weight in experimental group, respectively on the average. Time-span to maximum
bleeding volume was 1 hour and 40 minutes土 20minutes on the average in control
group, and it was 1 hour and 50 minutes土 30minutes on the average in experimental
group. Spontaneous returning time in control group was 2 hours and 40 minutes on the
average, and it was 2 hours and 50 minutes土 40minutes on the average in experi-
mental group. Time-span to 30 per cent spontaneous return was 4 hours and 50 minutes
士 50minutes on the average in control group, and it was 5 hours and 30 minutes土
60 minutes on the average in experimental group. Although these results are scattered
in considerably wide range, they show similar tendency to each other revealing no marked
difference between control and experimental groups, even when the results obtained dur-
ing summer is excluded considering the influence of seasons, as mentioned in the above.
Twelve hour survival rate in control group was 7 /16 (45 per cent), and 7 /14 (50 per
cent) in experimental group. Twenty-four hour survival rate was 0 per cent in both
groups. Namely, animals in both groups showed definitely similar results. Towards the
time of 30 per cent spontaneous return, hematocrit ratio and portal pressure began to
show obvious tendency of increase. FRIEDMAN and FrNE20l explained this finding to be
due to increase in intrahepatic vascular resistance from the findings of hepatic angio-
graphy. Moreover, from the fact that from this stage hepatic Qo2 rapidly decreases, it
is assumed that hemorrhagic shock becomes irreversible in this stage45>. In this respect
also, the r田 ponsewas similar in control group and experimental group to each other.
Uncountable studies have been carried out on regeneration of residual liver parenchyma
after extensive hepatic resection, and it is considered in general that the liver, which has
accomplished regeneration, has nothing different from normal liver in histological appea-
ranee, cellular constitution and its functi0n27l. However, it is considered that reconstruc-
tion of intrahepatic vascular system is markedly retarded, despite early recovery in liver
weight and its function43>. This fact is understood from the results of the present ex-
periment that portal pressure in control group was 125土9mmH20 on the average before
288 日本外科宝函第35巻第2号
the withdrawal of blood, whereas it was obviously in a higher level of 146土7mmHρ in experimental group, on the average, when the blood within the bottle was returned at
the time of 30 per cent spontaneous return. Recovery of portal pressure after the blood was returned at the time of 30 per cent spontaneous return was slightly higher to be 120
per cent in experimental group compared with that of 110 per cent in control group, being
suggestive of larger vascular resistance of the intrahepatic portal system in experimental
animals than in normal ones.
As has been discussed, an organism having regenerated liver did not show any re-
cognizable difference in the result of hemorrhagic shock by the modified method of LAMSON and WIGGERS’method when compared with normal animals, despite its disadvantageous
condition in hepatic circulation as presumed from the findings of portal pressure in the pr白 entexperiment. Accordingly, it is at least assumed that the dogs with regenerated liver is in no way inferior to normal ones in the response to hemorrhagic shock, though
it is a little excessive to say that the dogs with regenerated liver is more resistant to shock state of this kind than normal ones.
V. SUMMARY
In order to study the attitude of organism having regenerated liver following hepatic
resection against hemorrhagic shock, hemorrhagic shock was produced by the modified
method of LAMSON and method of WIGGERS’in dogs having 2 month aged regenerated liver after 50 per cent hepatic resection. By the comparison of the results in these animals
with those of normal ones, the following results were obtained.
1) In maximum bleeding volume in hemorrhagic shock by WIGGERS’method, sig-
nificant difference could not be observed between control and experimental animals. Twelve and twenty-four hour survival rates were 6/11 (54 per cent) and 2/11 (18 per
cent) in control animals, while they were 5/9 (56 per cent) and 2/9 (22 per cent) respectively in experimental animals, revealing no significant difference between these two
groups.
2) In the experiment of hemorrhagic shock by modified method of Lamson, all the
animals of both groups survived more than 24 hours, when the blood was returned at the time of 15 per cent spontaneous return, and when the blood was returned at the time of 30 per cent spontaneous return, all the animals in both groups died within 24 hours after withdrawal of blood.
3) There was no significant difference between control group and experimental group
in maximum bleeding volume, time-span to maximum bleeding volume, spont釦回usre-
turning time, time-span to 15 and 30 per cent spontaneous return and 12 and 24 hour survival rates, regardless of the time of return of the blood within the bottle either at the
time of 15 per cent or 30 per cent spontaneous return in the experiment by modified method of Lamson. Namely, significant difference could not be found out in the attitude of animals between these two groups in reversible and irreversible phase of hemorrhagic shock.
4) Portal pressure in experimental group was higher before withdrawal of blood and recovery rate of portal pressure after returning of the blood within the bottle was a
REGENERATED LIVER AGAINST HEMORRHAGIC SHOCK 289
litter higher than in control group, suggesting a little larger vascular resistance in the in-
trahepatic portal system.
5) Changes in hematocrit ratio in experimental group showed similar tendency as
in control group, revealing no significant difference from each other.
6) From these findings, it is assumed that the dogs with regenerated liver show
the similar response to hemorrhagic shock as control dogs without revealing inferiority in
this respect.
Accomplishing the pr田町tpaper, the author is deeply indebted to Prof. Dr. Ichio Honjo for his encourage-
ment and valuable advices throughout the cou日eof the present experiment.
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(* in Jn問問)
REGENERATED LIVER AGAINST HEMORRHAGIC SHOCK 291
Fig. 15 At the Time of Spont. Blood Return
Control H. E. ( x 150)
Fig. 17 At the Time of 30% Spontaneous Blood
Return Control H. E. (× 150)
寸限切1記~-~監犠咽,主活葱'F..ll回..,,翁U祉,、,u:馳~~ヨ
Fig. 14 Before Bleeding Regenerated Liver
H. E. (× 150)
Fig. 16 At the Time of Spont. Blood Return
Regenerated Liver H. E. (× 150)
Fig. 18 At the Time of 30% Spontaneous Blood
Return Regenerated Liver H. E. (× 150)
292 日本外科宝函第35巻第2号
Fig. 19 At the Time of 70% Spontaneous Blood
Return Control H. E. (× 150)
和文抄録
肝再生犬の出血ショ ツクに対する態度
金沢大学医学部第2外科学教室(指導:本庄一夫教授)
辻
近年肝悪性彊疹等に対し肝広汎切除が広〈行なわれ
るようになるにつれ,再生肝の病態生理が臨床的にも
一段と注目されるようになった.肝切除後の残存肝は
暫時高度の肝障害に陥るにもかかわらずよくそれに耐
え著しい肝再生を行ない,その重量は急速に切除前値
に接近する.
一方今日では生体に加えられる侵襲に対し肝が最も
重要な役割を演ずる臓器の一つであることは,よく知
られた事実である.されば肝障害に耐え著しい再生を
行なった再生肝は再び侵装が加えられた場合,正常肝
に比し抵抗性の冗進或いは減弱などの特異性を示す
か,否かは興味ある問題である.かかる観点から50%
肝切除により作成した肝再生犬及び正常犬を用い,著
しい肝障害をもたらす出血ショック をWiggers法及び
Lamson変法により作成し,再生肝の病態生理の一面
を窺わんと意図し次の織な結果を得た.
1) Wiggesr法による出血ショックに於てP 肝再生
犬群,対照犬群の聞に最大出血量, 12時間及び24時間
生存率に関して,何ら有意の差異を認めなかった.
2) bmson変法による出血ンョックに於て15%自
然還血期返血を行なった群では,対照群,肝再生犬群
の何れも全て24時間以上生存し, 30%自然還i血期返血
政 彦
を行なった群では,対照群,肝再生犬群の何れも全て
24時間以内に死亡した.
3) Lamson変法に於ける15%自然還血期返血群及
び30%自然還血期返血苦手の何れに関しても,最大出血
量,最大出血到達時間,自然還血開始時間, 15%及び
30%自然選血期到達時間, 12時間及び24時間生存本に
於てp 気温,気候及び性別による影響を考慮しても,
肝再生犬群と対照犬群との間に有意の差を見出すこと
が出来なかった.iWち出血シ司ツクの可逆相,不可逆
相に於ける両群の態度には有意の差異を認めなかっ
fこ.
4) 門脈圧は肝再生犬群に於てはp 出血前値に於て
も,出血により下降した門脈圧の返血後回復率に於て
も,対照群に比しやや高値を示し,門脈系血管抵抗の
やや大なることを示唆した.
5) ヘマトグリット値の推移は肝再生犬群と対照群
とはほぼ同様の傾向を示し有意の差異を認め得なかっ
fこ.
6) 以上により肝再生犬は出血ショックに対し正常
犬と同様の態度を示し,正常犬に比し明らかにショ ッ
ク耐性を有するとは言えないまでも,決して劣るもの
ではないと言える.