CHANGES IN THE BLOOD NH3-N LEVEL AFTER...

TitleCHANGES IN THE BLOOD NH3-N LEVEL AFTERLIGATION OF THE HEPATIC ARTERY, WITH CHANGESIN THE HEMATOCRIT RATIO

Author(s) MIYAZAKI, TOYOKI

Citation 日本外科宝函 (1960), 29(1): 177-204

Issue Date 1960-01-01

URL http://hdl.handle.net/2433/207058

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University

CHANGES IN THE BLOOD NH3-N LEVEL AFTER LIGATION OF THE HEPATIC ARTERY, WITH

CHANGES IN THE HEMATOCRIT RATIO

by

ToYOKI MIYAZAKI

From the 1st Surgical Division, Kyoto University Medical School (Director : Prof. Dr. CrrrnATO ARAKI)

(Received for publication Sept. 26, 1959)

INTRODUCTION

177

HERRICK and others!0),24> pointed out that in annular nodular liver cirrhosis the

causes of portal hypertension followed by accumulation of ascitic fluid were (1)

that hepatic vein branches were compressed by regenerating liver nodules and (2)

that the elevated hepatic arterial pressure was transferred to the portal pressure

through free presinusoidal communications between hepatic arteries and portal veins.

They also made it clear that in cir・rhoticliver the rate of blood司owin the artery

had a relative increase as compared with the normal liver.5' On the other hand,

MARKOWITZ15' et al. found that postoperative penicillin could lower the mortality of dogs deprived of hepatic arterial blood supply by preventing massive liver necrosis.

In 1951, RrnNHOFF,28> BERMAN and othersu reported that the ligation of the hepatic

arter~ァ in a case of cirrhosis with ascites caused a decrease in ascites and improvements

of other clinical findings.

In our clinic too, in order to investigate clinical application of the ligation of the

hepatic artery, a series of experimental studies have been performed on changes

following the ligation, especiallJア onliver necrosis, in both normal dogs and those ascitic ones which, hemodynamically, are similar to those with cirrhosis.26' In parallel

with these studies, I tried to investigate the ammonia metabolism after the ligation

of the hepatic artery. Some invcstigators13＇・rn>.isihave reported that coma, which田cursin liver cirrhosis

or in EcK fistula, is often accompanied b~γan elevation of blood ammonia level, and

that administration of nitrogenous substance to patients with hepatic disorders may

cause neurological and mental disturbances similar to hepatic coma.12>•14> The blood ammonia level has come to play an important role in the development of neurological

and mental disorders in hepatic diseases. Experience tells us about the di自cultyof drawing blood from peripheral vessels

after the ligation of the hepatic artery. TANTURI and others29> also reported that the

ligation of the hepatic artery caused hemoconcentration, the degree of which was of some help in predicting the prognosis of the dog. According to MooN and others,11>

this hemoconcentration means a decrease in the circulating blood volume. Thus in the 1wesent stud~· ， the determination of hematocrit ratios was performed tog-ct her with that of blood ammonia levels, so as to observe hemoconcentration after the

178 ．日本外科宝函第29巻第1号

ligation of the hepatic artery and an aspect of the systemic or hepatic circulation.

(In the following page hematocrit will be referred to as Ht.)

MooN defined“sh凹 k”asa type of circulator:.・ failure, not central but peripheral in origin, characterized by decreased blood volume, and decreased volume flow and

by hemoconcentration, and thought that hemoconcentration was caused by l開 kage

of plasma due 白 abnormalpermeability of systemic capillaries. In recent years,

however, concerning the cause of hemoconcentration in“shockぺtherehas been a tendency to put much emphasis on local leakage of plasma in the damaged part.9"19'•31'

EXPERIMENT ON ANIMALS

I Materials and Methods

(1) Animals. Adult mongrel dogs, weighing about 10 kg, were used. They

were fed chiefly on carbonhydrate diets, but given nothing but water within 12 hours

before the experiment.

(2) Where and how to take blood samples. Peripheral vein blood was drawn

from the hind limb, arterial blood from the femoral artery, and portal and renal

vein blood from the portal trunk and the renal vein respectively by laparotomy.

As the anticoagulant, 2 to 3 mg of potassium oxalate per 1 cc of blood was used.

The potassium oxalate had been made NH3 free by re-crystalizing in an alkaline solvent with 10 to 11 pH.

(3) Method of measurement of blood ammonia. A modification of CoNw AY’s microdi町usiontechnique2'•4> was employed. Ammonia was indicated by the amount of nitrogen it contained. A CONWAY’s microdiffusion unit was prepared with the central absorbing chamber containing 0.7 cc 0.0002 or 0.001 N HCl, with TASHIRO’s reagent as indicator. The outer chamber contained 1 cc blood, to which 1 cc saturated

boiled K,COJ was added. After covering it with a glass lid, the unit was rotated

20 times for 20 seconds to mix up the solutions, then put aside to incubate for 10

加 20minutes at room temperature. Barium hydroxide (Ba (OH) 2), 0.0004 or

0.002 N, delivered from a horizontal pyrex, micrometer driven burette; was used to

titrate excess acid. The end point was set at 5.4句 5.6pH where the indicator

became colourless. Using this technique titrations of controls and blanks were made

simultaneously. For the control, 1 cc of (NH1) 2 S04 solution, containing 2r /dl or

10 r/dl of nitrogen, was put into the outer chamber, and for the blank, 1 cc of

distilled water was used. To these solutions ・ 1 cc saturated boiled K2COJ was added to get end points of the control and the blank. With figures thus obtained from

titrations of bloods, controls and blank日， thenitrogen content of the blood ammonia

was calculated according to proportion. The results were then corrected by CoNWAY’s correction table, refering to the room temperatures and periods of incubation. The figures thus corrected were taken as the blood ammonia levels.

(4) Measurement of Ht. ratios. As the anticoagulant, 2 to 3 mg of potassium

oxalate per 1 cc blood was used. The blood to be measured was put into a羽T1NTROBE’stube till it rose to 100 in graduation, then centrifuged at a frequency of 3,000 r. p. m. for 30 minutes.

BLOOD AMMONIA AND LIGATION OF HEPATIC ARTERY 179

(5) Operative technique. Intravenous nembutal anesthesia (0.3句 0.5・cc per kg) was used. By means of the technique established in our clinic, the common hepatic artery, right gastric artery, and gastr吋 uodenal artery 'Vere doubly ligated and divided. Investigating the arterial collateral pathways to the liver, URABE and lsHIGURO made it clear that the ligation of these three arteries interrupts most of arterial blood supply to the liver, leaving no e汀ectivearteries enough to prevent liver necrosis.

In order加 produceascitic dogs McKEE’s method was employed. Under closed inhalation anesthesia thoracotomy was performed to reach for the thoracic inferior vena cava, which was slightly constricted by a cellophane band. 2 to 3 weeks later those dogs in which ascites was produced were further subjected to the ligation of the hepatic artery brie臼ymentioned in the above.

II Results (1) Changes in the blood ammonia level after drawing of blood (Fig. 1, Table

When blood is drawn and left in air, the ammonia level shows a rapid increase

until 3 to 5 minutes after the drawing. Then it continued to rise progressively but very gradually. So in the following measurements performed on animals and clinical

cases, care was taken to complete the procedure of adding saturated K2COJ to the

blood drawn and put into the outer chamber of the incubator between 5 and 10

minutes after drawing blood. The am-

monia concentrations in peripheral vein

blood obtained from 32 control dogs lay

between 36 to 84 r/dl, averaging 51

r/dl. (2) Physiological changes in the

ammonia level in peripheral venous blood (Fig. 2, Table 2).

For investigation of diurnal variations

Fig. 1 lJemonsu同志onぜcha，炉 int恥』，foodNH, N levels ojter sheddin/l Mood

100

日Fh

（H品

vt勺JhWN也久吋州

w N

i~ ミミ，、司〉ミミ、ug ～ cq

0 0 130' 5’ 5’ 10’

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刀ote Bl.ood wαz taken f'om per併e皿Ju-ein

Table. ! a. Chan叩 sin Mood Nfl.rN fey-,むaj＆忌ts1i沼・ading_blood.

ηote:Bt.田-xiwa昌弘陵n一悶mperipheral v-ein. 事~ indicates m1告はitesai_t社主並立5ldi.の•q.

E五If v MゐーN!e山ls(ρ'Voザ（：；〕tゐ一Y日

業/.30’ d’ 5 ／。! ! 0干 32 48 55 55 56

z 11 ! Z6 38 40 d.5 dq

.3 γi Z8 48 54 .SS 55

4 72干 4 7 6Z 75 78

5 ャ l .3 8 68 8.3 宮守

6 γl 45 守4 8 1 Eワ宮q

γy 1 ! 26 41 68 6 8

8 6 干 Z守 .sz 69 ケ5

刀7ean 33 55 66 69

15’

7込le.I h. Peripheral blood N!h-;)I !eve！.史迎。in 32 normαf dog_s.

4 6 '"19 69 6 1 40 50 62 47

5 6 4.J γ6 53 50 γo 62 46

sz 44 6 7 45 .3 8 6 6 84 S8

4Z J 8 62 45 7Z 6ケ S8 f、A

T!!!lE.竺住持主主主

第I号第29巻日本外科宝函180

119. 2. P!Jysio{o!Jk:at chanyes付与iood.

NHrN tev-ets.

Di w・nat Chan Jes くt)

so

80

心認）

hMgと＼〈ーや『＼〈、

8N句

Tahle Z. Physio ／，哲i

陥Do，対Q ~』土融8a.m. !Oam. n,即n rρm. 4R'fl. 6p.m. v正面：~喧lionゲ・s.

1 10 1 46 45 J8 J7 42 41 』’γ』 46? 14 1 ヲq ヴZ ’15 84 ヲs 84 ワZ~84

3 7 1 69 63 64 68 62 ?2 63ぜh ?Z 4 11 干 6 7 65 6 1 6 4 6 6 ウ4 6プ－ヴd

s 7 干 40 45 s 1 46 45 42 ao~s1

6 8 1 SO SS SO 51 58 Sヲ so-s 8

(!) Diurnal ch叩'Jes.

30

〆亡、

~ Lノ師、、sIll 為、》、、aミミ，． ;:i ミ

in the level, the measurement was per－ごformed at an interval of 2 hours from －~ 8 a. m.加 6p. m. The range of the Q:5 30

variations turned out句 be8 to 13 r/dl, a.φ増 dfet 30 SO SO 凶with 10 r/dl on the average. In order Time (minutes）αfter tた dietto observe if eating would influence the level of blood ammonia, meas~rements were made before diet, and 30, 60 and 120 minutes after it. The result was that the

variation was within the range of 6旬 16r /di, with an average of 11 r/dl. Thus

physiological variations in the ammonia level in peripheral venous blood were around

10 r/dl, a little exceeding the analytical error of土 3r/dl.

(3) The ammonia levels in main blood vessels (Fig. 3, Table 3）・

The ammonia levels in peripheral arterial and venous blood were much the

same, ranging from 40加 80r/dl, the former being slightly higher than the latter.

As for the portal vein blood, the level stood between 232 and 607 r/dl, 194 to 541

r /dl higher than the level in peripheral venous blood. The values for renal vein

blood were 120白 266r/dl, exceeding those in peripheral vein blood by 58 to 221 r/dl.

6p.m 4p.m

Cl1an(J邑sdu.e to diet

2p_m. γ芭">On10am

(2)

8αm.

~岬l勿~t 制区除別•1::tち〆出’ IZO’ Ran3e g戸υOJlations.

7 ヴ i62 54 53 56 s 3~6 2 z 10 ! 4ヶ 44 48 54 44~54

3 14 干 56 63 63 s z sz-66

4 8 干 43 51 5'1 45 43 ~、 S

181

Fig 3. Blood N砂川e向tsく切t)1n main hlood vessels.

BLOOD AMMONIA AND LIGATION OF HEPATIC ARTERY

芯hte.3. Blood M母Nlevels (o/cil) in main blood vessels.

及盟 Wt. .,,,, Po1ta.t F註＇ifhe皿t,. 加.・Gゆ、m vein 叩 inDijf即応E

乙主乙~~ ιι＿.！.

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down. The cause of the ascent, as he asserts, is that adenosine in blood is decom-posed by the function of adenosinedeaminase. To investigate this point many experi-ments3o>,3z>,37J have been made, in all of which the blood ammonia level as it stood

5 to 10 minutes after drawing was considered as the ammonia level of the blood

samples.

KOPROWSKI and UNINSKim reported that the blood ammonia level and revelation

of ammonia in blood after drawing were much the same with dogs as with man. My present experiment has come旬 asimilar conclusion. Accordingly, the amount

of N in ammonia determined between 5 and 10 minutes after drawing blood was

taken as the ammonia level of the blood sample. 羽TmTE,MoTONAGA23J，、

in the ammりnialevel of peripheral vein blood in healthy adult persons. This report

has been supported by the result of my present experiment. It has been known

that between the ammonia content of peripheral arterial and venous blood there is

so little di百erencethat it barel)' exceeds the analytical error. Some reported, how-

ever, that a rise in the ammonia level in arterial blood was followed by an appreciable arterio-venous difference in' the ammonia content.30>,39> Therefore, in this study,

about 30 hours after ligation of the hepatic artery measurements were performed on arterial blood.

Compared with the values of peripheral blood ammonia, those of portal and

renal venous blood ammonia come out remarkably high. This is proof that the

intestines and kidnc~· are the chief sources of blood ammonia. On the other hand, there are many reports that the ammonia content of peripheral blood is much the

734 74 5

第 1号

same as that of hepatic vein blood.23>,3o> All these join to support the existing

knowledge that the liver is the chief organ which dispose of ammonia.11>,16>

(4) Changes in the blood ammonia levels and Ht. ratios in normal dogs after

the ligation of the hepatic artery (Fig. 4, Table 4).

Ligation of the hepatic artery was performed on 13 normal dogs, all of which died within 30 hours postoperatively, revealing necrosis in the liver at autopsy. In

7 of them, the blood ammonia levels were followed up till their death. About 60

minutes after ligation, no marked changes in the level were observed. However, after

3 hours it began旬 risegradually until at the 6th加 10th hour it reached a level

40 to 70 r/dl higher than the initial level. Then it went on with slight variations,

and about 60 minutes before death a sudden, rapid increase took place. In 11 dogs

the values of blood ammonia went up as high as 170 to 4 70 r /dl just before death (Fig. 11).

Serial determinations of Ht. ratios were performed on 3 dogs. The Ht. ratios

began to rise immediately after the ligation, and 60 minutes later showed a 10%

increase over the initial level. In Nos. 5 and 7 dogs it further increased by 4 to

5% bεtween 3 and 10 hours following the ligation, after which it disclosed a slight tendency to decline. In No. 6 dog, however, the level did not show such a tendency, but only a slight variation upward or down.

第29巻日本外科宝函182

F19. 4 G7i中3回 in.bit.叫 NH.rNtevets in notmat必7,JSafter the lnterru.J向。n寸hepaticarteワ凶；thchan3es in f沼ma.to何 t峨珂．

ノ1~9寸 13

~ fO ! ~ E 、ノ1 何．I .S> I +;o I tj I ・久

: ~ャl 匂 TI ~ u ~ i; "'' ,o

－一一桝一Nくmeanゲヶcases) j「；一一一一一地mat"ocrlt"ratio ! ~

(meanゲJc，仰のi除、十・N匂－Nteuelsi 11.s"t .6ef:Jte tた deed持！者

v ~ i 聖正！サミ帝: srs_ 24 ~ .~

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50

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宅＼〈Eohh刈

21 18 15

Time (hours）αfter t五eJ刀為ttψtion.

12 9 b 3

．．


T a.Ue. 4. C/Janyes mゐfoodNfli-N te四~ts in nofmat do(p ajt訟 theintenu.戸or.寸hepatic 也市町四thchan:1es in hematocrit 同~tios.

~ex附g）~伽NH:FN feuef:古切6むぜt忌！＇f"nおけはpち。n.

四nゲ＇le~f月u:;:,nl 3 s 6 'Yao Cf 10.担 12 15 1'8 21 22 t砂7.Inc.同 ase酔 Dec.同 aseafter the，市 rrup恥

来1356'1.Jo"Iρ＇30 12 15 18 21 ?A

1 q i 47 47 4 ,3o pointed out that fluid transfusion increased the amount

of blood of not only systemic but also hepatic circulation. So in the present stud~－， in order to observe how such transfusion would in日uencethe blood ammonia levels

and Ht. ratios, 600 cc of 5% glucose or balanced electrolyァtesolution were injected drip by drip into the femoral vein in 5 dogs for a period of 2 to 3 hours, bεginning

fi/j-5. Changes in .htood NHrN levels after ti恰 co.城市右on寸thehepa,tlc: veins wi；柏 changesin

hematocrit tal:ios.

not:e : Blood出（］$taken／.同mt恥j宅問問'1.a白守‘

ー－NlfJ-N No.1 一一－ He mat。crittaf／，。

i" I 5 ！拘! .9

陥1j 15 ~ !... I ~、ー寸

I N ＿..－－’－－－－N;il ~ _/_/- ~ 10 世

Ir----- I ~ I lli l ミ

! s c::

l ！~ －ー』＂＇雨宮？

、·~

mi'nu:tes after the con剥 cち帆刊

第 l号第29巻日本外科宝函184

五ぬSChan在sin .btood NHs-N Le ，叩~ts ojtE貯 t加constriction

185 BLOOD AMMONIA AND LIGATION OF HEPATIC ARTERY

Fi9. 6.α Chaザesin blqod NH3-N levels in doJS tee・'d1linJfluid 古川町fusion ザたrthe int吾川1ptionゲ初ehepαtic atおとメ

note Blood. wasゐ伽fromthe femoral arお7・十： let.Je，ゐJustbザ0ぽ thedeath.

ノ F[ufdtran~片tsfonσ勺tucoseorB.Eぷ600cc)

《Hu

n－

－MWぬMU恥

washkh

ト；，，.5(No.4)1t115

18 15

Hoursゲ加 thestartゲ戸uidtransjusゎn.

40

20

~ 10 §-

。士

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旬、。、，

186 日本外科宝函第29巻第1号

To.hie. 6. Chaザesin hゐod.NH.rN le11e!s and hemaioC'rit ta.tios in the cα ゲ戸uidtranザμ伽10おfヴhou.tsザterthe interruption of the hψαticαbワ 7時 81.ood叫 taKEnf馴内向仰lart，吋

~凶·~.(l勿

187 BLOOD AMMONIA AND LIGATION OF HEPATIC ARTERY

fiJ・吃a.Chan3es In Mood NHr N le四・tsin do JS which昌弘rl/IV


忍lie."!.h. C百αrJ_CfeSin .Mood M局ーNtelleゐmdogs wich .sw"vfved the intenu.ptlon of ti伝んepα托 α品ヴJ,ytheadmtnis1:ta古・onザpenlcitlin.

~·位'ff-。Z匂u3おX' 12 ! z 15 ! 3 e千

4 10平

也師母、

四りかethe Blood Nf右ーNtewtsC招0after the intenuption. inte付upt.油業 7 3 A 5 そY 8 11 14 Zf ?5 3Z

58 60 62' 5ケケ0 65 63 6~

ヴ5 84 88 守3 ケ6 ヴ5 宮0 B’y

44 41 53 4q 45 50 44

53 52 58 58 6Z 60 66

55 48 51 51 58 65

ね品市 Indicate電 d吋saji主vthe ini及川向。n.

Blood wむも険n/rompeパpheratvein.

暴ふ0.,

Ag. 守ゐ． Chanses inゐ1foodN~－N fa四1{sin do3s which swviued tli削 ntenupn制of the陥'Paticarte守.hythe ad mini stばt1onof penicl ttt n.

． "' 、、，S 長10，・

、る叫．民

モ主予ーミ！-.q ~ o~ 々々辛口、~ ~ ·~ I -0 叩」E E・議刈心 10

旬。~ 20 tJ 者ノ

．．．．．．

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．． : ． :. ．．．．

I I 10 15 20 25 30 ．

JJays ajtet ti民同etru酌 n.

the 12th hour, after which, gradually declining, they returned to the preoperative

levels at about the 24th hour after the ligation. Furthermore, in 5 dogs the levels were observed after the 24th postoperative hour (Fig. 7b, Table 7b). The blood

ammonia levels showed a slight increase in some cases from the 1st till the 5th

postoperative day. The increase, however, was a little over the range of physiological

changes. In comparison with the fate of control dogs (which died within 30 hours after the ligation), that of most dogs operated on may well have been d田id凶加fore

the 15th postoperative hour. This makes us realize that penicillin is n民間関町 onlyfor a short period after the ligation of the hepatic artery.

(8) The ammonia tolerance tests by means of intravenous injection of ammo・

nium chloride (NH4Cl) in penicillin treated dogs that survived the ligation of the hepatic artery (Fig. 8a, h, Table 8a, b).

After intravenous injection of 2.5 cc per kg of 1 % NH4Cl solution, the ammonia levels in peripheral blood were followed up to observe the function of disposing of

ammonia. In 11 normal dogs the levels returned nearly to the initial ones 20 minutes after the injection. On 4 of the 6 penicillin-treated surviving dogs NH4Cl tolerance

tests were performed. From the 1st till the 5th day after ligation the return to


Tぬle.8弘 Ammonium tolerance tests in notmal，伽'JS

功toUJh intraueno邸 NH4Cli苦邑ction.

189

~°！ tゆft. s町内－Nte回 ts1?the NHf血N ；；~~：何（抑）afternterrupt，信 irzjection "・ 5’，o’ IS’ zo’

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z 6 4 758 143 110 88 194 γq d6 at z 宮宮 385 ?38 I’γ8 128

3 6 z ?53 人:16 89 "14 19／グ'4 zザ 12 3 ’Y 8 395 24ザノff't 145

4 sγ 201 ノ15 85 てY9 144 Sii Z宮 zz 4 93 4ヲ6 24ぐr 212 ノ＇61

6 76 263 ノ＇4Z 守8 8 4 18"/ 66 zz 8 ’γ ケ6 386 zzケノ66 1/7

8 65 Zd.6 ノII 86 6／ノ8146 21 4 守 Eヨ 33’Y l'!Z ，ぽ8 ノ08

No. 3. dog. 八M dog

bysゲ＆ttfle清涼叩1四例ぜt計t小h；’ψe~zion. 15' 20’ ，

Days lncte田 eor decre<

rr；加，：’勺15.’'l'I;；~。ndecrea:;e

ran. 勾6与1scyt1!1l而Befoぜ ret/le ~~ ；；：＂；＇／／，~悌Oa》 ler

n恥 uption. intem;ptio1ワ?tem;ptior JゲeelJon 5’ 10’ 15' zo’

5 53 23ヲ 154 105 ’Y8 ノ86IOI 57 ZS ／ sz Zi;J 13ヲヲ＇！ 'IS

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14 so zzヨノ06 'Y4 59 ／ツ'3S6 ?4. 今／／ 58 14ヤノ03 5'1 6ヤ

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77ote I. Z.5 cψ::te臨世d即時

ゲ5伊’山10’iゲノ：.c~刷0 315 ／，’I SI 75

4主5201 135 ザ2

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31’Y 16ヲノI/ 6"1

4()3 154 119 6官

a10 1s1ヲ＇O 41

254＂倒品 i'5

U肘制se世 d配柑¢decrease

雪1:＇’怯10~ ；＇！／｝c~；161 Bγ4ケ 43

ノイ74ヲ5 d6 di

fl'! 45 Z3 9

今吋吉守 t守’o

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meαnゲflほ ses.

P、ミヨ!:"-

宮

寺＇＿ I回ぜ

"' l 靖

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100

Firt. 8a, Ammonium tolerance tests in norma.l

- dザsthtol!Jh intra.venous MぬCti rj ection.

I • note zs作ザf万NH4C[s山 tion叫 3I int，αvenous!v in ・ected.

300 L __ －－~ Blood wasおいJ'om仲村eta.t1230「一一一" i:: h、

200

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the initial levels was delayed. A week after the ligation, however, it was observed to have been restored to the preoperative state.

(9) Changes in the blood ammonia levels and Ht. ratios in dogs which survived the ligation of hepatic artery by the application of acetylcholine and atropine at the operation (Fig. 9, Table 9).

NAKASE in our clinic made this experiment for the first time. An acetylcholine shock was produced before the ligation of the hepatic artcr~・ so as to decrease hepatic ferritin beforehand. After the ligation atropine was given to suppress the release of hepatic f erritin from the anoxic liver caused by ligation. The occurrence of liver necrosis was preventαl and the mortality diminished. lh this way he made it clear


Rg. 8...b.3. Ammoniumfolerano電testin No.J dog. F守8.li4.Ammonium tolerance test In Na4 d,勺

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五.ble.

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- NHJ-N .; iミ7こでこ加山門trat;o i 10

i5

第 1号

Chanqes ;n.htood N~－N [eve!s and hematocrtt ratios in dogs wich survived thei~おけは向。nojti恥 hepatic arfetyゐyAt叩T吊 andAcを，ty/choline Ji1!en at the intettup恥 n.

note

第29巻白木外科宝函

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that hepatic ferritin plays some role in the development of necrosis. Thus in the present study, 100 mg acetylcholine was intravenously injected on

the previous night and 3 hours before the ligation of the hepatic artery. After the ligation, 0.5 mg atropine was given every hour for 10 hours. Two of the 4 dogs survived the above mentioned experiment. In these two, the blood ammonia levels were observed up to the 24th hour following the ligation. During the period from the 3rd till the 8th hour and towards the 12th hour, the levels showed an increase of 33 to 46 r /dl and then returned to the initial levels.

The Ht. ratios rose 8 to 9% from the 60th minute till the 5th hour following the ligation, after which they gradually dropped to the initial levels where they remained after the 12th hour in all cases but one in which the level went farther down.

From the above, it seems clear that the fate of dogs been decided before the 15th postoperative hour.

(10) Changes in the blood ammonia levels and Ht. ratios in出 citicdogs after the ligation of the hepatic artery (Fig. 10, Table IOa, b).

In Nos. 1 and 2 dogs the ascites was removed by paracentisis on both the day and the previous night of the ligation in order to lessen the changes in abdominal pressure which would be caused by the intraabdominal operative procedure at the

operated on had already

193

Charwes川 foodM持－Nte'l!et宮 andhemαあcritra向的価cit?c匂占after the interruption oj the hepa殉 α必ヴ

刀oお： Btoodw回初enftomtheyらmota.lan匂一一－－Hematoctit (mean of 8ca包む一一一川－N(m伽 of8ca旬。！十： Ntt3-N tewfsjuiC .bφe thedep,扮i Iii

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time of the ligation. The blood ammonia levels increased by 20 to 40 r /dl fr官 n

the 9th till the 21st postopeative hour, but were restored旬 thepreoperative levels

after 24 or 30 hours. No. 1 dog died accidentally on the 3rd clay and No. 2 dog

died of peritonitis on the 7th day postoperatively. In Nos. 3 to 8 dogs the ascites

was not removed before the ligation. In most of them the blood ammonia levels

showed a temporary increase of 20 to 50 r;dl during the period from the 3rd till

the 6th postoperative hour, after which they declined nearセtothe initial levels. And just before the death, as high a level as about 150 r /dl was sudden1yア reached

in all cases except No. 6 dog. No. 7 dog was a little different. Although it showed

a preoperative level of 90 r /dl, a little higher than in the other ascitic and the

normal dogs, it remained within the range of 90士 10r / dl until its death.

人日 innormal dogs, the Ht. ratios rose in all the 8 cases after the ligation,

though in Nos. 1, 5 and 7 dogs the rise was of a slight deg1・c::.In Nos. 1 and 2

dogs, the levels decreased nearly to the initial ones on the 2nd da~· . after which no

changes were observed till they died. In Nos. 3 to 8 dogs the increase in the Ht.

ratio was not foilowed bv a decrease in it.

On gross examination at autopsy, no caぽ

them showed congestion of high de広1・cc.

(11) Comparison between the blood ammonia

but most of

before the just

l i vcr necrosis,

l℃ached lじ＼＂Cl日

revealじcl


Tai>!e. 10. a. Changes in .htood NHrN te哲也fsin ascitic dogs after the intenu戸onof the hepati，巴 artery.

Dog. °；；~ （，械l/t.As·〔c/JesS•副r総為骨，n 叩 t叫（泌it)ajte1-tllc枕 1-tuptlon.

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千 6 8 53 81! 118 103, fl'! 80 93 ケノ 56 61 68

キ目白押，y君 S548 SO 56 43 54 6l 千 90 79 86 103 80 100’Y6 9

BLOOD AMMONIA AND LIGATIONυF HEPATIC ARTERY

On the other hand,, in normal dogs 1100

the ammonia level after the ligation 1000

of the hepatic artcr~ー is at highest 100

to 150 r /dl. About 60 minutes before 受 ~00

the death, it showed a sudden, rapid。刷increase as high as 1 70 to 4 70 r / dl.号It is similar！＼ア observedin the ascitic ..§叩

dogs and the dogs which received日uid~ 600 transfusion after the ligation of the ~ hepatic artery : the ammonia levels g 500 showed a rapid rise, reaching 60句 150函 .WO

r I dl and 86 to 200 r / dl respectively, 羽目but not so high as in normal dogs. It

may be properly assumed that the rapid

rise in the ammonia level were not due

to a rapid advance in degeneration of

liver parenchyma but due to a high

degree of hepatic as ＂℃ 11 as systemic

circulation impediment at the agonal stage，の forit would be unreasonable to suppose

such a rapid advance of the degeneration in such a short time.

The dogs (with ligation of the hepatic arter~· under the administration of

penicillin) could endure as high levels as 200旬 1200r /dl for 30 to 60 minutes,

whereas the normal dogs died as a result of the ligation with ammonia levels of

170 to 4 70 r /ell, and the dogs receiving fluid transfusion and the ascitic ones died

with lower ammonia levels. From this, it is clear that the increase in blood ammonia

level and its duration after the ligation of the hepatic artery is not the direct cause

of their death.

The lowest levels which could be main司

tained for 30 or 60 minutes without

endangering their lives were 200 to

1200 r /dl or 200 to 900 r /dl respec-

tivel~·.

195

fig. fl Blood川 -Nlevels ju.st .hりも＇＇etたdea.t1itn dOf!s 凶 ththe inおnuptionoftたhepa許ca rteヶα,Jthe {owes!: te11e{s lasおdJもPJO Of 60 minutes In ammon伯m お／era.neeTests /,y ,oral inta々 ojNf主Cl.

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Tahte. !Z. R;ripheta! ii恥 aM局ーN!ez;ets and hematocnt ta1:!os

in正1eatthyadult petsons and pai:ien.おwithll1.t€t diseases.

(1) I加f特叫ttpeばons. (2) Patient量wit持tivetdisease.

Fi9. fZ. li!rlphetat ゐtood.内－Nte~.

200

in加 tthyadutt petslTIS and

pa11en£s with liuer di.sea犯s.

的 m 今e伽助N御物抑制t幼m』l/jQ Sex D即時・eM常細？治勢M

m ..ヨ30 ~ . 411 43 χ ＇；［ .46千.Lil/ftcl川崎 1q3. 34

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~.χ ， 23 ヰ 68 38 JC 0 33,t ,. 53, 52

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Ta.Me I J. Charwe s in .ht()()d NH,-N teu.必 and伽・atるcritra1:1os after t加初めrup伽

ゲt加 hepaな α必ryinpa汐entswith liver cirrhosis accompanied .hy asci.tes.

r:u.t信nt&x ~ifti ~／：；，山pψ’ i:o,. Days ajte,. ti.駕 1hte汁也ption‘acre 3 ’1 ff 14. 2! 28 39 5’7 ”'10 85 "5 fO'I

Case. I千同噸 1守3 守q 93 8 8 124 9ヴ 100 86 90 102 12ヴ 12'0 84 112 x. J. レJ伺 ato-46 Ctit-R(% J4 3 4. 4 0 3 8 44 40 37 32 33 32 32 33

制。昭島『E 58 112' 56 53 't2 ？ヶq十

7.宵L 'Hema to・42 Ctit-R(Yo 22 25 25 26 2'1 25 43

C仰 3干'ifvH3－時di 宮4 84 81 107 守6 65 汁，、1J. n

~~'rt~正tくoう－〈28 3γ 35 35 36 32 38 33 白 se4 ~ fWも－Mfd.1 so 53 so 45 sz SI 'X. 0 Hemato-

33 Ctit－時 52 6/ 54- 53 sz 44

刀ote Antecu.bitat vein .blood wαs dtawn atajcαstiザ sti必 mthe earかmo.州 ngatl the c釘凶作ceptCase 2. areαtive Jjor the present，バprlt1 1959 Cαse 2 a1ed of U1-em1a on 14肋 dり・

200

150

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20


F与13 Chan(JeS in以oodNlfJ-N levels ajiゐ theinte山内on寸thehep ztfc atfety in patients凶 thtiuet cirrhosis accompanied /Jy田:cit忌S‘

Case 2 T・2?''1NH,-N {eve!s ?hou.ほloeforenet death.

197

胎内yof• Bザ・orethe 7 14 21 28 39 57 70 85 95 108 hospiおf;Ja合'Of? 初tetn;.p許on

Days ajte炉 t民 int.哩川向。n

ammonia level to decrease from 193句 99r /dl in Case 1, and from 92 to 58

r /dl in Case 2. In Cases 3 and 4, however, no such decrease were observed (Fig. 13, Table 13) .

Cases 1, 3 and 4 were followed up until April 1, 1959, that is 109, 28 and

21 days after the ligation of the hepatic artery respectively. The blood ammonia

levels showed a slight increase over or decrease against the preoperative level. The

fluctuation was at most within土 25r/dl in Cases 1 and 3. They once showed

a temporary increase of 25 and 23 r /dl respectively within a week after the ligation,

after which they remained no higher or a little lower than the initial level. Case 1,

however, again disclosed an increase of 27 to 20 r川lfrom the 70th through 85th

postoperative day. In Case 4 the blood ammonia level remained within the range

of 50 ± 10 r /dl, with little changes.

The Ht. ratios showed a vcr~γlittle fluctuation except in Case 1, which revealed a 3 to 10% increase about 2 weeks after the ligation.

In Case 2 the blood ammonia level rose to 112 r/dl 18 hours postoperatively,

but later dropped to 53 to 56 r /dl where it stayed from the 3rd till the 7th day.

On the 11th day it again began to rise and on the 14th day, 9 hours before her

death as high a level as 279 r /dl. About 2 days before the death, this case disclosed

such町mptomsas oligm匂， amarked increase in blood N. P. N. and mental confusion.

人tautopsy, histological examinations revealed that there ＼＼℃re no necrotic changes

in the liver but hemoglobinuric nephritis in the kidney.

198 日本外科宝函第29巻第l号

DISCUSSION

In normal dogs, the ligation of the hepatic artery bring about a high anoxic

liver not only by interrupting arterial supply of oxygen to the liver but also by

producing portal circulatory disturbance. From this anoxic liver develops a necrotic

liver through a high degree of parenchymal degeneration, as URABE, IsmGuRo, NAKASE,

MrYAWAKI and others have experimentally shown. On the other hand, NELSON, ErsEMAN7J •22J ・ 23 ）・ 27J and others pointed out that the hepatic function to dispose of

ammonia is failed with a general anoxic state of the liver and with a high degree of parenchymal degeneration, not to mention with a decrease in the hepatic blood flow.

In normal dogs, a ligation of the hepatic artersア causea 40 to 70 r /dl increase in peripheral blood ammonia 6 to 10 hours after ligation. Symptoms which imme-

diately follow the ligation are congestion of the liver and, as to the quality of blo叫

hemoconcentration, that is, a rise in the Ht. ratio, as a forerunner to an increase

in blood ammonia. If the view is to be held that hemoconcentration which soon

occurs is due to local leakage of plasma into the damaged part, the hemoconcentration

which immediately followed the ligation is considered as a result of hepatic circulatory failure, that is, stasis.

If there was no bleeding worthy of mention during the operative procedure, an

incr印 sefrom 30 to 40% in the Ht. ratio with it any bleeding will have made the

amount of plasma equal to 25 % of the total blood volume leak out of the ssアst疋mic circulation system. This condition may well be called “shock”. And such an increase in the Ht. ratio was observed in all cases after the ligation. In some cases

the blood ammonia level showed a temporary decrease about 60 minutes after the

ligation. This phenomenon can be explained b：－，ァ thereport that there is a temporary

spurt in the activity of urea synthesis (in the liver) at an early stage of shock.刻

In order to see how rapidly the disturbance of the hepatic circulation would

a古田tthe blood ammonia levels and Ht. ratios, congestion was experimentally pro・

duced 同 constr匂tingthe hepatic veins. The blood ammonia levels and Ht. ratios

increased rapidly. On the contran, when fluid transfusion, which would increase

the blood volume of systemic and consequently hepatic circulation, was applied after

the hepatic arterial ligation, the ammonia levels and Ht. ratios in peripheral blood

declined for a while. These facts prove that the hepatic circulatory disturbance is

one of the cause of the increase in the blood ammonia levels and Ht. ratios occurring after the ligation of the hepatic artery・

The decrease in the blood ammonia levels and Ht. ratios caused by the fluid

transfusion did not last. This may be partly because the transfused 5 % glucose solution, balanced electroiyte solution swiftly leaked out of the circulation sys旬m,

and partly because parcnchymal degeneration was ever advancing in the liver.

In those dogs which survived the ligation by penicillin or atropine and acetyl-choline, the blood ammonia levels and Ht. ratios in’the blood once increased following

the ligation, but after 9 to 12 hours I℃turned nearly to the initial levels. The return

to the initial levels m叫V be explained in this wav : in these cases, a hepatic

199

circulation impediment, temorary as it was, occurred, deprかingthe liver of its oxygen

supply; but par℃nchymal degeneration was not advancsd to a very high degree, so

that the circulator~· disturbanc::; rεcovered before long, when the liver had adapted

itself to the hepatic circulation bγthe portal blood only. If the liv亡1・welltolerated

the ligation of the hepatic arto・~·， it does not necessarily mean that is would im-

mediate！~· recover its normal function to dispose of ammonia. Ammonia tolerance

tests performed on dogs ＂’hich survived the ligation re＼ァealedsome degree of impedi-ment to the function which lasted for about a week after the ligation. FRASER and

others8> obtaincd similar rcsults from thymol turbidity tests, bromsulphalein clearance

tests etc.

In ascitic dogs, from 3 through 6, or from 9 through 21 hours following the

ligation, the blood ammonia levels showed a temporar~· increase. Otherwise, however,

they stood around the initial levels. This proves that these dogs have the same

adaptability to the hepatic circulation by the portal blood only as had those dogs

which survived the ligation b~· the administration of penicillin etc. This findings

also accords with the following observations which the investigators in our clinic

have reported. NAKASE found that the liver of ascitic dogs already showed a marked decrease in hepatic ferritin before the ligation of the hepatic artery, so that little

was left to b巴 releasedafter the ligation. HosoNo observed a lasting increase in the

rate of the portal blood flow, and ADACHI an increase in the oxygen content of the

portal blood after the ligation.

BLOOD AM'.¥IONIA AND LIGATION OF HEPATIC ARTERY

ぺF14 Chaぺ9esin .Mood NH;-N levels after the川 erru.ptfono} the hepa.tic artery. Note.

ι ←一－ Ascitic dogs (mean of 8 cases) ー一ー一－ Penicillin treated survi,・ing dogs

(mean of 5 cases) 『－ - Control dogs (mean of 7 cases) Blood was taken from the femoral artery.

也同

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h・・4

60

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15 ↑E

Houts

3 8 5 3


Autopsy disclosed no necrotic changes in the liver. In only two of the 8 dogs,

however, the Ht. ratios returned to the initial levels after a while, with the other

six holding the increased levels. This may be explained in the light of the autopsy

finding that all the 8 cases had congestion in the liver.

In Fig. 14 a comparison is made between the postoperative blood ammonia

curves in normal dogs and in ascitic dogs or the dogs which survived ligation of

the hepatic artery with the help of penicillin. In normal ones, the rise is not

followed by a decline until the death, while in the others, a temporary rise is brought

about by a hepatic circulatory failure due to the ligation. This circulatory failure,

however, does not develop into parenchymal degeneration, but the liver comes to

adapt itself to the circulation by the portal blood only, with the result that the

ammonia levels soon return to normal.

On Clinical Cases

In most cases with liver cirrhosis or BANTI's syndrom, the ammonia levels in

peripheral blood are generally higher than in healthy adults, but in some cases they

remain within normal range. The difference may have occurred because the ammonia

levels varied according not only to the degree of hepatic parenchymal damage the patients suffered, but also to the anatomy of the shunt between the systemic and

the portal circulation.

In cases with cirrhosis accompanied by ascites, ligation of the hepatic artery

cause little changes in the ammonia content of blood, just as had been expected from the results of the experiments on ascitic dogs. KITANI and others14> pointed out that

in cirrhotic cases with high blood ammonia levels, antibiotics, such as streptomycin

which are effective in suppressing intestinal bacteria, prevented the production of ammonia in the intestines, lowering the ammonia level in peripheral blood. This

was proved lηァ Case1 in the present study. The patient had an ammonia level of

193 r /dl when hospitalized, but administration of streptomycin brought it down to

99 r /dl just before the ligation of the hepatic artery. After the ligation, it remained

within the range of 99士 25r /dl ・・・ much the same level as before the ligation .. even though no antibiotics were given. This means that the hepatic functions

once impeded had been recovered by the ligation. In this case the ligation had been

performed for the purpose of decreasing the ascites. The purpose was attained;

both the circumference of the belly and the serum bilirubin decreased.

In Case 2, 18 hours after the ligation of the hepatic artery the blood ammonia

increased from the preoperative 58 r /dl to 112 r /dl. The increase, however, may

be explained by the fact that a large amount of preserved blood, containing 320 to

500 r /dl of ammonia, was transfus:.:d during the operation. Thi日 ca日c had been

unconscious for 2 da~·s until she died, showing a blood ammonia level as high as

279 r I dl 9 hours before her death. These findings may give the impression that she died of hepatic coma. From the results of various clinical examinations and

au top町白ndingsit is obvious that the cause of the death ＂’as uremia. And the increase in the blood ammonia le＼＇じlmay be explained in this ＂’a" : the increase in blood N. P. N. caused an increase in amine, which was detected as ammonia


according to the method of measurement of ammonia employed in the experiment.

SUMMARY AND CONCLUSION

The results of the above experiments and tests and findings of the clinical cases

are summ吋 upas follows :

(1) In normal dogs, the ligation of the hepatic artery cause a 40 to 70γ／dl

increase in the blood ammonia level. About 60 minutes before death, the level went

high up to 170 to 4 70 r /dl. The Ht. ratio also showed an increa田 of10加 20%.

If fluid transfusion was performed, the blood ammonia levels and Ht. ratios de-creased

for a longer or shorter time, and moreover the blood ammonia level just before

death showed a decrease, with 86 to 200 r /dl.

(2) In those dogs which survived the ligation of the hepatic artery by the

help of penicillin or atropine and acet~· lcholine, the blood ammonia levels and Ht.

ratios revealed a temporary rise after the ligation, but soon returned to the initial

levels. In the dogs which survived with the help of penicillin, the function to

dispose of ammonia was restored to the preoperative state one week after the

ligation.

(3) In the ascitic dogs, the ligation of the hepatic artery caused a temporary

increase in the blood ammonia level, which was ぽlOnrestored to the initial level.

But it again increased rapid ！~· just before the death. The Ht. ratios were not

di百erenton the average from those in normal dogs. Two of the 8 dogs returned

to the initial levels on the 2nd da~·s after ligation, and two others showed a slight

increase in the Ht. ratio. (4) In all dogs, the increase in blood ammonia level observed after the ligation

of the hepatic artery was not the direct cause of their death.

(5) In the 4 cases with liver cirrhosis accompanied by ascites, the blood

ammonia levels remained much the same after the ligation of the hepatic artery as

before, with the exception of one case which died of nephritis.

From the above mentioned facts it may be concluded that when normal dogs

died after the ligation of the hepatic artery, the increase in the blood ammonia

level which is not followed by a decrease is not the direct cause of their death.

The increase has been brought about by the hepatic circulatory disturbance combined

with parenchymal degeneration. On the other hand, when the dogs survived the

interruption of arterial blood flow to the liver, the increase in the ammonia content

of blood lasted onl~・ for a while after the ligation, in parallel with hepatic circu-

latory disturbance. A similar tendency was observed in the ascitic dogs. The clinical

cases with liver cirrhosis accompanied by ascites tolerated well the ligation of the

hepatic artery, unless liver cirrhosis was accompanied by a high degree of renal

insufficiency. These cases faced no danger of hepatic coma due to the interruption,

maintaining their pr印 perativelevels of the blood ammonia.

I was very fortunate to have the enthusiastic guidance and support of Prof. Dr. CmsATO ARAKI and Assistant Prof. Dr. Icmo Ho:;.10 throughout this study.


REFERENCE

1) Berman, J. K. et al.: Ligation of the Hepatic and Splenic Arteries in a Patient with Atrcト

phic Cirrhosis of the Liver. Arch. Surg., 63, 379, 1951. 2) Conway, E. J.: Microdiffusion Analysis and Volumetric Error. Crosby Lockwood and Son

Ltd., London, 1950. 3) Conway, E. J. et al.: Blood Ammonia. Biochem. J., 33, 457, 1939.

4) Conway, E. J.: The Ammonia of Normal Human Blood. Biochem. J., 29, 2755, 1935. 5) Dock，明日 TheRole of Increased Hepatic Arterial Flow in Portal Hypertension of Cirrhosis.

Tr. A. Am. Physicians, 57, 305, 1942. 6〕 Fuld,H.: Uber Die diagnostische Verwertbarkeit Yon Ammoniak Bestimmungen im Blut.

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和文抄録

肝動脈遮断後の血中アンモニア値の変動

（附，ヘマトクリット植の変動）

京都大学医学部外科学教室第1講座（指導：荒木千里教授）

宮崎豊基

Rienhoff等により創始されたp 腹水を主訴とする

肝硬変症に対する肝動脈遮断術についてはp 賛否両論

が相対立している．当教室に於てもp その臨床的応用

を検討する為に，各方面より検索が行われており，そ

の研究の一環として，肝に於て特異的に尿紫合成によ

り処理され，他方最近肝性昏睡の原因として重要視さ

れる血中アンモニア（以下「ア」と記す）を指標として，

肝動脈遮断後の肝機能の変動をp 実験lミ並びに臨床例

について追究した．尚遮断後の全身循環状態の一面を

窺う為にp ヘマトクリット値（以下「へ」値と記す）を同

時に測定した．

実験方法： J也中「ア」値はConway氏微量拡散法によ

りp 「へ」値は Wintrobe氏法により，実験犬では主と

して股動脈血，臨床例では肘静脈血について測定し

た．尚血中「ア」値の採血直後3～5分間の急激な増加

の傾向を考慮して，採血後5分より 10分の聞に検出し

た「ア」の窒素量をもって，血中「ア」値とみなした．肝

動脈遮断は教室の術式により，総肝動脈p 右宵動脈p胃

十二指腸動脈を紡紫，切断した．腹水犬作製はMcKee

氏法により，胸部下空静脈を狭窄した．

実験並びに臨床成績

(1）正常犬及び健康成人の末梢血の「ア」値はp 夫々

40～80y/dl, 40～701/dlで，その生理的変動は 101/dl

内外で，測定誤差（士3γ／di）を僅かにこえる程度であ

った．

(2）正常犬で無処置の場合p 血中「ア」値は，遮断後

6～10時間後より p 持続的に40～70γ／di増加し，死亡

直前には更に急激に増加して170～470γ／diに達した．

この死亡直前の血中「ア」値はp NH4Cl経口負荷試験中

30分又は印分間の辰低維持値200～1200〕／diに比し透

かに低値が含まれており，遮断後にみられる血中「ア j

の増量そのものが直後の死因でないことは明らかであ

る．

「へ」値は遮断直後より持続的に10%内外噌加した．

尚全例30持間以内に死亡しp 種々の程度の肝の看護血及

び壊死が認められた．

(3) 肝動脈遮断直後より門脈の血行が停滞すること

が確められている．他方p 正常犬で肝静脈を狭窄し，

肝を後血させるとp 血中「ア」値p 「へ」値共に急激に増

加する．そこで，肝動脈遮断後輸液を行って，肝流血

量を増加させると p 持続時間の長短はあるにしても，

血中「アMl宣，「へ」値共に術前値近くまで減少する．こ

のことは，遮断後の血中「ア」値及び「へ植の増加の原

因の一つは肝の血行障害であることを示している．

(4) 肝動脈遮断lこ際して，乏酸素肝よりの肝Ferr-

itinの遊離を抑制し， I血行の障害された肝が犠死に陥

ることを防ぐPenicillin又はAtropineを投与して生存

した犬ではp 血中「ア」値，「へ」値共に遮断後3時間よ


り12時間に亘りp 一時的に20～50}/dl増加するがp そ

の後は略々術前値に復帰し経過した. Penicillin投与

により生存した犬の「ア」処理機能を， NH4Cl経静脈

負荷試験により検すると，遮断後 1週間前後は，血中

「ア」曲線の負荷前値への復帰は遅延するが，その後は

術前と全く差異はなくなる．

(5）腹水犬では，血中「ア」値は，遮断後3時間より

6時間に亘り，又は9時間より21時間に亘払一時的

に20～501/di増加するが，その他は略々術前値にと

fまる．これらの腹水犬は肝動脈遮断後一時生存する

が，肝壊死発生以外の原因でその後死亡し，その際血中

「ア」値は死亡直前に急激に増加する．「へ」値の変動は

対照犬と同様の傾向を示すがp その増加の程度は対照

犬に比し軽度のものもあり，中にはPenicillin投与下

で生存した犬の如し術前値に復帰したものもある．

(6) 臨床例 4例に於ては，術前より合併した腎炎の

悪化のため死亡した l例を除き，術後3～15週間を経

た今日まで，術前値の50～ 1201/dlを維持しており，特

に第1症例はp 術前の S.M.投与により減少した血中

「ア」値をp 術後は S.M.の投与によらずとも維持して

し、る．

以上の成績を肝動脈遮断後の肝壊死発生の機序に関

する教室の知見一一即ちp 肝動脈を遮断すると，門脈

の血行障害を来しp 肝は極度の乏酸素状態に陥り，こ

の乏酸素肝が肝壊死発生の基盤となるーーと併せ考え

ると，犬が肝動脈遮断により死亡する場合の血中「ア」

値の持続的増加は，遮断直後より起る肝血行障害に続

く肝実質障害によるものと考えられる．

他方p 犬がPenicillin又はAtropine投与により肝動

脈遮断に耐えて生存する場合，血中「ア」値は遮断後短

時間一時的に増加するがp その後は術前値に復帰して

経過し，門脈のみによる肝循環に順応したことを示し

ている．遮断に際してPenicillin等の投与により生存

した犬におけると同様の傾向は腹水犬に於ても認めら

れP 更に臨床的に，腹水を主訴とする肝硬変症はp 高

度の腎不全を伴わ'2る限り，肝動脈遮断によく耐え，

血中「ア」値も術前値を維持し得て，肝性昏瞬の危険は

ない

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