EXPERIMENTAL STUDIES ON EXTRACORPOREAL CIRCULATION … · Seeking after the cause of death, we have...

Title

EXPERIMENTAL STUDIES ON EXTRACORPOREALCIRCULATION WITH ARTIFICIAL HEART-LUNGMACHINE, WITH SPECIAL REFERENCES TOIMPROVEMENTS OF THE CIRCUIT AND APPARATUS,AND TO HISTOLOGICAL INVESTIGATION

Author(s) TATSUTA, NORIKAZU

Citation 日本外科宝函 (1962), 31(3): 404-430

Issue Date 1962-05-01

URL http://hdl.handle.net/2433/205442

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University

404

EXPERIMENTAL STUDIES ON EXTRACORPOREAL OIR-CULATION WITH ARTIFICIAL HEARl'-LUNG MACHINE,

WITH SPECIAL REFERENCES TO IMPROVEMENTS OF THE CIRCUIT AND APPARATUS, AND TO

HISTOLOGICAL INVESTIGATION

by

NORIKAZU TATSUTA

From the 2nd Surgical Division, Kyoto University Medical School (Director : Prof. Dr. Y ASUMASA AoYAGI) Received for publication Mar. 15, 1962

INTRODUCTION

The open heart operation for complicated heart diseases can be performed safely only

when su自icientduration of cardiac arrest or heart lung by-pass is acquired. However, on

this point there are many unsolved problems in the hypothermia and extracorporeal

circulation.

Many investigations in this area have been performed in our laboratory. HIKASAe,io・n,12・13・w,SHIROTANI38'39>, TOMIOKA 46>, SAITa32l and Kuw ANA 19) proposed that specific preme-

dications were e旺ectiveto cardiac function under hypothermia, and good results have been

obtained clinically. On the other hand, 0GATA23・24l et al. produced a new type of pulsatile

pump and TAKEDA 45l, NoNOY AMA 22l, IDA 16J and SASAKI25J emphasized the necessity of

pulsatile flow during the extracorporeal circulation with this pump. Apd they published

that pulsatile flow during the extracorporeal circulation was safer for body than non-

pulsatile flow, especially when the flow rate is lesser than lOOcc/kg min. or prolonged

circulation over 30 minutes was requsted.

But SASAKI35) noticed that this machine was not enough for clinical appli国 tion,so

we made present experiments aiming at getting survivors after perfusion.

Seeking after the cause of death, we have improved the instrument of the artificial

heart-lung machine, in the course of these experiments.

The purpose of this paper is to show the improved points of the instrument and

also describe the patho-histological findings using these circuits.

CHAPTER I. EXPERIMENT AL METHODS

Artificial heart: We used a pulsatile pump, although we used a sigma motor pump

in the first stages of our experiments.

Artificial lung : At first, we used foam-oxygenator of WAUD・SALISBURY33・34・49)type,

then we improved this oxygenator and produced a form of the film oxygenator. However,

later the bubble oxygenator of double cylinder type has been used which was designed

by SAEGUSA28J et al. of Tokyo University and made by Nippon Junkansochi Kenkyusho.

Circuit : The circuit employed in this experiment is shown in Fig 1. There are

EXTRACORPOREAL CIRCULATION 405

some di旺erences between the case where

the bubble oxygenator was used and other

αses. Material of circuit was vinyl-chloride

tube at the first stage, but later we used

silicone gummi tube. And silicone coating

was also employed for metal and glass

portions.

Experimental animals : Mongrel dogs

weighing 6～13 kg. were used.

Anesthesia: After intravenous injection

of pentobarbital sodium (20～25mg/kg),

trachea was immediately intubated with an

endotrach田 ltube for the closed anesthesia

with ether and pure oxygen.

Priming blood : Heparinized blood ( 4

mg/dl) of 1,000～1,500 cc was taken from

non-anesthetized donor dogs.

Later P.V.P. (polyvinylpyrrolidone),

lpsilon (antiplasmin drug) and A C.D. (acid

citrate dextrose) solution were added to

priming blood.

In the case with A C.D. solution,

calcium gluconate was added to the perfu-

sing blood before stop of perfusion. Perfu-

sion was further continued for some time.

Cross-match-test between donor and

recipient dogs was not performed.

Fig. 1 The perfusion circuit

vpu Afu with double cylinder oxygenator

・・ with 1νAUD-SALISBURY type foam oxygenator, or our五lmoxygenator

一－ without oxygenator AP arterial pressure, SP pressure of sagi tal sinus, CP : cerebrospinal pressure, IVP inferior caval vein pressure, VC vena cava, VBR : venous blood reservoir, Ox : oxygenator, VPu : venous pump, APu : arterial pump, BT bubble trap, F : filter, FA : femoral artery

Desinfection: The inside of the circuit was washed with clean saline sCJlution, but

sterilization was not performed.

Autopsies : Autopsies were performed immediately after death in the dead cases,

but in the survival cases, dogs were kept alive for 48 hours after perfusion. In all cas白

a detailed histological examination of the liver, spleen, kidney, adrenal gland, lung and

brain was carried out. Hematoxilin-Eosin stain, Sudan III stain and NrssL’s stain were

performed.

Arterial blood pr・田surewas measured by the STATHAM strain gauge electric manometer

at femoral artery. Inferior caval vein pressure, and pr回 suresof s:i.gital sinus and cere-

brospinal liquor were measured by means of polyethylene catheters which were induced

to each portion and connected to water manometer.

The electrocardiographic lead II and occipitofrontal electroencephalographic lead were

recorded、

CHAPTER II. COURSE OF EXPERIMENTS AND RESULTS

The process of experiment is divided into following groups:

406 日本外科宝函第31巻第3号

Exp.

Table 1 Partial perfusion without arti五ciallung

？い

1Timじ り［

Re>ult death ( hりur"!

Pump 1…e I Perfus I time I トauseof death;Improvement cc／匂.／min.I (minutes) I diathesis

15 I 10 I 仲 Ihemo出 agic I I i 甘 1diathesis ’

hemorrhagic diathesis 品！aria]embolism

4 I died 15 pulsatile

5 I died V

目・0

t

o

m

gu m

gb

ca η4

1

20

6 I died 5 ! pulsatile 25

7 I survived 剖gmamotor 35

8 I died 3 I sigma motor

9 I survived pulsatile 30

Group I : Partial perfusion

(A) Partial perfusion without arti五ciallung

(B) Partial perfusion with artificial lung

(C) Rapid cooling by A-A shunt

Group II : Total perfusion

(1) Group I. (A) (Table 1)

IO -lit

10 川柑

hemorrhagic diathesis

10 silicone coating

silicone coating

silicone coating

IO 五larialembolism

IO

As we expected from 0GATA23'2ペTAKEDA~s>, NoNOY AMA 22>, IDA 16' and SASAKI's35'

papers, all animals died due to bleeding in the thorax and from the slight wound of nasal mucosa at the first stage of our experiment owing to the very strong hemorrhagic diathesis after perfusion. Two factors would be pointed out as the cause of such hemor-rhagic diathesis, namely vascular factor and blood factor. At first we noticed blood factor, and then in order to solve that problem, Fig. 2 The circuit of group IA (partial perfusion

we have performed the experiment of without oxygenator) extracorporeal circulation without arti五ciallung in the circuit, which was suspected

to be a large cause of blood destruction

(Fig. 2).

In these cases, venous catheters were

inserted from jugular vein and femoral vein

to caval veins and thoracotomy was not

done. However, hemorrhagic diathesis was

found greatly after only 10 minutes perfusion

and we could not r田 cuethe animals from

death by bleeding from the operation wound

and slight wound which was made in the

nasal mucosa at the time of inserting the

cannula for oxygen supply after operation.

Histologically, severe bleeding was four】d

in the liver (Photo. 2), spleen (Photo. 7),

JV : jugular vein. FV femoral vein, FA : femoral artery. VBR : venous blood reservoir, APu : arterial pump, BT : bubble trap. F；品lter.

EXTRACORPOREAL CIRCULATION 407

Fig. 3 E.E.G., E.C.G. and arterial pressure wave in the case of no. 6

Fig. 4 Arterial pre州 ure in the case of no. 6

F判 何！±＇~ ~；~ r ，－寸 T l ι 1 ・

Mい向、州八r..，..，，，吋J吋し4品

の＼／

州州＃仰山川」1111以

IZO

40 20

0 0 s p.t引p....

p私＇I10

20 30 10 soιo m崎

/I)し~仙川川UしJし伽Mん叫 川..I~む1) ~句cas泡s,we notic定dno change in E. C. G.

f'""tf吋iuhm pod争u-fa.su凡

10 ..... 再ー

and E. E.G. during perfusion, but animals

died from severモshockafter perfusion and

low voltage was observed in E. C. G. and h寸十寸「 T T 「 矛芯Fヤず市~ζみよ人 E. E.G. in this stage (Figs. 3 and 4）・

No di任erenceswe日記enin the rモsuit

of pulsatile and sigma motor pump as the

artificial heart.

出l山川州刷AMU凶刷ルU,州札刷仙 From these facts we presumed削 the下叫－ -v--一 一 - r ...... r 十’~ hemorrhagic diathesis w出 causedby dest-

山山川以品仙山川以Alv川向山w川 N叫川川州J ruction of blood component due to materials

・ ・- ・--・ of circuit or blood taking method from

donor dogs. Following ABE’s reportu, who was my coworker, silicone coating was per-

formed on the reservoir and glass and metal portions of the circuit. After that, hemorrhagic

diathesis disappeared and we succeeded in making dogs live long.

2) Group I. (B) (Table 2 and Fig. 5)

We performed partial perfusion with oxygenator of WAUD-SALISBURY type which

had been used by OGATA et al. In these伺 ses,hemorrhagic diathesis after perfusion was

Table 2 Partial perfusion with art凶ciallung

Artificial I Exp. I I Time of I I Flow rate Perfusion I I 1 I No. IR叫川 death I Pump I ~~－ j r ~~~~e !Cause of death¥ improvement ung ! No. I I (hours) I Iα／kg./m. (minutes) I I

I 10 I di吋 I25 I sigma mo伽 I 35 I 10 I ~h~~rfusi Waud司 I I l I I I Salisbury I I I I I l , type I I I ,J I i I I P：，~： p.

' I survivedl 一 Ipulsatile I 35 1 10 I - I anttlasmin I I I : I I drug

Our film oxygenator

12 I survivedi I pulsatile

13 I died I 26 I pulsatile

25

45

14 I surviv叫一 IP山山｜ 50

Bubble i I I I type I 15 I survi吋－ I pulsatile I 40

In all αses of this group, silicone coating was employed.

25

mihar infarction

//

//

，，

’F

408 日本外科宝函第31巻第3号

not seen and the electrocardiographic and

electroencephalographic findings were almost

normal during perfusion, but we could not

r白 cuethe animal from the death by shock

of unknown回目白． Furthermore, the no-

ticeable finding in these 伺 S白 wasgreat

increase of secretion from nasopharyngeal

region and this phenomenon was considered

to be based on vagotonia due to intoxication.

Great fibrin deposit was also found in the

oxygenator at the contact site of blood and

oxygen and at the same time the reduction

of fihrinogen content in blood was notable

り. From these results, we performed the

same experiment in which lpsilon (antipl-

asmin drug) and P. V .P. were added in

the priming blood for the purpose of

detoxicating the toxins derived from blood

destruction in the artificial lung, and then

we succeeded in keeping dogs live long.

The substances which団 usevagotonia

Fig. 5 The circuit of group IB (using WAuo-SALISBURY type foam oxygenator or our 品lmoxygenator)

APu JV jugular vein, FV femoral vein, FA femoral artery, Ox oxygenator, APu : arterial pump, F : filter, BT : bubble trap

are yet unknown but they will be produced with blood destruction by bubbles. The

blood of the preceding experiment remained a little in spite of powerful washing because

such type of oxygenator are used repeatedly. We consider that the remaining blood is

denatured into toxic substances. Therefore, we conclude that such type of oxygenator

can not be used safely in the clinical operation.

To prevent the blood destruction by bubbles, screen or membrane oxygenator is

considered to be adequate4・7・17). Then we manufactured a film oxygenator which was

modi五ed from WAUD-SALISBURY type of oxygenator (Fig. 6). Glass-balls in 2～3 cm

diameter with silicone-coating were filled in the oxygenator as shown in Fig. 6. The

venous blood drops down from the upper portion and produces the thin五lmof blood

over the surface of glass balls. The oxygen blows into the oxygenator from the bottom.

Oxygenation of blood is performed on the surface of glass balls. We succeded ・in getting

the survivors by using this oxygenator However, from the viewpoint of the capacity of

oxygenation, this oxygenator was inferior to the foam oxygenator of WAUD曙SALISBURY

type We were able to get the su伍cientoxygenated blood in the series of experiment of

partial perfusion under 300cc/min. of flow rate, but according to YAMAZAKI's51> report,

who was my coworker, it was impossible to get enough oxygenated blood in the series

of experiment of total perfusion of group II with our film oxygenator in which flow

rate was over 40/kg/min.

This type of oxygenator was thought to be impractical because very large instrument

would be necessary in clinical cases. Furthermore, in spite of complete silicone coating

on the glass balls a few fibrin clots were found, and infarct in the liver (Photo. 4) and

EXTRACORPORE人LCIRCllL.¥TION

kidney (Photo. 12 and 13) was seen hist-

ologically in the case of no. 13 which was

performed without filter. At that time we

got the new oxygenator of bubble type

which was designed by SAEGUSA et al.

(Fig. 6). This oxygenator is small-sized

and contains the五lterin it, so does not

require seperate debubbling chamber, and

we are able to renew the oxygenator in

every experiment.

In these experiments, blood destruction

was lesser than with WAUD『 SALISBURYtype

oxygenator. In the point of oxygenation,

this type of oxygenator was superior to

五Imoxygenator. But slight destruction of

blood was unavoidable and production of

五brinclots by stirring the blood with bubble

was also seen a little.

Since then we have used this type of

oxygenator because this is thought to be

Fig. 6

←bl師 4 〆ぐ＝・－IJ岨4

t.ltu

left WAUD-SALISBURY type foam oxygenator center our film oxygenator right double cylinder bubble oxygenator (SAECUSA et al.)

best among the many typ田 ofoxygenator which we can get easily.

409

We succeeded in getting long term survivors in the experiment which was performed

with this oxygenator for 25 minutes of partial perfusion. When we employed this oxyg-

enator, we added a venous blood reservoir and venous pump to the circuit as illustrated

in Fig. 8.

3) Group I. (C) (Table 3)

While we were studying the problem of oxygenator, we had a series of experiment

of rapid cooling by arterio-arterial shunt. The purpose of this experiment was to eliminat怠

the dangerous accident caused by oxygenator and to shorten the time of conventional surface cooling.

The pulsatile pump was used as artificial heart. Blood was taken out from femoral

Table 3 Rapid hypothermia by A-A shunt

Exp.! 1Time。f:Minimal! Minimali Cooling I Rewarming I Perfusion I I Inserting side N ! Result I death I I I ti悶 I time ! • tim間但 Cause of dea叶ofthe arter凶o. i 1 (hou吋 t~.T. （℃） IR工（℃lj (mir

16 I died ' 2 18.5 I 24.5 I 33 I 87 I 120 I cardiac failure I left

17 I died 3 1 23.0 I 25.7 I 51 I 75 i 126 I unknown I left

18 I died i 5 20.4 I 21.0 I 58 I 80 i 138 I unknown I left 19 I died

20 I died

21 I 刊rvivcd•

22 I survived.

5

7

22.9 24.3

15.8 20.0

22.0 24.5

22.0 19.8

E.T. esophageal temperature R. T. rectal temperature

45

32

24

46

53 98 unknown left

61 93 unknown left

41 65 right

87 133 right

'In all cases of this group, p. v. p. and antiplasmin drug were added in the priming blood.

410 日本外科宝函第31巻第3号

artery and infused into carotid artery. Heat

exchanger was manufactured by us. It

consisted of silicone gummi tube which was

immersed in constant temperature bath

(Fig. 7).

As a premedication animals were given

essential fatty acid, Vit. E. and dimethyl-

aminoethanol by mouth during 5～7 days according to the method of HIKASA9'10・11・12・

丸比19，払紙乱45>et al., The results were shown

in Table 3. Effectiveness of this heat exchanger

was inferior to metal heat exchanger which

was reported by HARRISON-BROWN3) and

P!WNICA 26).

The time of cooling and rewarming

was considerably long as a result of partial

perfusion. At the time of cooling 2～5

minutes were needed to get down 1°C of

body temperature, and 3、6 minutes to

get up 1°C of body temperature.

Fig. 7 The circuit of group IC (rapid hypothermia by A-A shunt)

HE

p CA・carotdartery, FA . femoral artery, BR blood reservoir, P pump, HE heat exchanger, BT bubble trnp. F filter.

Pumps are stopped for 10～15 minutes from the end of cooling to the beginning

of rewarming. During that time pulsation fell to 30、40per minute but heart never

stopped. Ventriculotomy was not performed.

The lowest temperature was about 15 8°～23°C in esophagus and was 19 8つ～257°C

m rectum.

When animals were rewarmed to about 33°～36 ° C at esophageal temperature, per£・

usion was stopped and then surface rewarming was continued.

Neostigmin was injected when the esophageal temperature reached to 28°～30°C in

the cooling phase, and promethazine was also injected after resuscitation. Perfusion time

ranged from 65 to 138 minutes.

One animal died from cardiac failure. Many animals died relatively early after

perfusion without awaking from anesthesia. The fall of activities of important organs

such as brain. heart etc. was supposed to be the cause of death, but from the microscopic

observations〆 itwas impossible to find pathological changes in brain, heart and so on. E. C G returned back to normal. In these series of experiments, the noticeable fact was

that two cases of long term survivors were inserted with the arterial cannula into right

carotid artery, while all the dead回 seswere inserted into left side. In the hemodynamic

view-point, we consider that right side delivery is reasonable for maintaining the perfusion

quantity to brain, because, in left side delivery cases, the flow from the artery pump and

that from heart meet and cancel each other, but in right side delivery cases do not.

However, even in left side delivery cases, we could not 五ndout any changes in the

brain with microscopic observation. Therefore, we can not help considering that histological

EXTRACORPOREAL CIRCULATION

Table 4 Total perfusion

411

Artificial

lung I fap. I l川 問 ofI Result death I fusion time Nι ｜一 Chours)I Cminutes) cc/kg./m.

γ－

o

m前

副

m

’i

g

b

山

ぴOω

Bubble

type

(double

cylinder)

，qA

U

J

U

J

U

O

L

a

L

a

L

O

L

・I・

－1

1

1

JHV

，dτ

G

，d

qJ4AFhdpnv

2

2

2

2

Fhd44AnL

d

d

d

ρ

L

ρ

、aL

1

1

4？・

l

，d

曹司叶・

d

η

j

Q

u

q

u

n

L

n

L

つム

30 I survived

31 I died

32 I died

33 lsurvived

，d

，G

e

e

－－－1

1日，口

dせ

Fhiu

n

J

q

3

36 I survived

つd

，d

，d

，d

，d

，d

e

e

e

e

e

v

v

v

V

V

・I

・

－

－1

・1

・1

v

v

v

v

，dv

u

山

山

田

・

日

U

s

s

s

s

，GS

7

9

1

2

3

4

q

δ

q

U

4

4

a

告

d

a

τ

4告

46 survived

2 10 35

戸、υnHuphu

q

υ

A

‘

qυ

日u

n

u

n

U

戸

h

v

p

、υ勺

t

F

b

n

U

R

υ

ハU

ハUn

U

A告

a告

44phU44τ4告

45

50

55

55

50

50

50

55

Cause of death

11) hem悦2) hyperthermia o f

blood

hemothorax

1) hemothorax 2) pulmonary edema

technical failure

herr

1) hεmo thorax I

2) pulmonary e《1引 11,, l I

hemothorax

unknown

insufficient transfusion

1〕hemothorax 1

2）五larialembolism ( I)

五larialembolism I 1)

!) 2)

l〕2)

1〕2)

I)

21

削 rnicalfailure I ~i

Improvement

1) electrocoagulation

）

）

）

1

1

1

II

II

II

3 n

U

A

U

n

u

l

－

－

II

II

1） グ2 ! silicone coating of

arti品ciallung

//

I/

//

II

I/

//

，， II

II

1) // 2) // 3) A.C.D. solution

1） グ2） グ3）グ

In all ca,es of this group, admixture of p. v. p. and antiplasmin drug in the priming blood, and silicone coating of glass and metal parts of the circuit were employed.

5

0

n

u

n

u

n

り

咽

ー

の

ん

の

ん

5

2

Fhd

戸、υZ1u

l

－

－

change such as dissolution of N1ssL bodies due to hypoxia does not yet appear immedi-

ately after perfusion.

We succeeded in getting the long term survivors in the right side delivery experi-

ments of rapid cooling by A-A shunt. But success or failure of this method depend on

the cardiac function of the animals. Therefore, application to the operation of heart

disease will be rather dangerous. Then we concluded that this method should not be

applied clinically to the operation of heart disease. However, the safety of our pulsatile

12

FhdFDRυ

1

1

1

12

18

15

30

30

30

30

30

30

412 日本外科宝函第31巻第3号

pump was proved.

4) Group II. total perfusion (Table

4)

Circuit are shown in Fig. 8. The chest

was entered through right 4th intercostal

space, and after heparinization and can-

nulation, partial perfusion was performed for

2～3 minutes, and then caval veins were

occluded and the venous return into heart

was completely stopped. We had a few

minutes' partial perfusion after ceasing the

total perfusion and then stopped the pump

and drew out the cannule. Intracardiac

manipulations were not performed. In four

experiments our film oxygenator was used,

but in others we used bubble oxygenator

mentioned above. Perfusion time was 10

minutes at first, then we extended the

length of perfusion time to 15 minutes and

30 minutes. Results are shown in Table

4. Nine out of twenty one dogs survived.

Fig. 8 The circuit of group JI ( uリngdouble cylin~er bubble oxygenator)

VPu A九CV caval veins, FA femoral arterv. VBR venous blood reservoir, VPu venous pump, APu arterial pump, Ox : oxygenator, BT : bubble trap, F 五lter

All animals which were perfused during 30 minutes survived except only one which died

from serious technical failure. Almost all causes of death were due to the intrathoracic

hemorrhage and filarial embolism at pulmonary valve.

Coworker’s ABE1' mentioned that the causes of intrathoracic hemorrhage was not

blood factor, but vascular factor. For the prevention of this bleeding we performed

electrocoagulation and strict mass ligation of operation wound and then the death by

severe bleeding after perfusion disappeared. Furthermore, we performed silicone coating

on the inside of the artificial lung to prevent blood destruction since the experiment No.

36.

Since the experiment of No. 44, we have added A. C. D. solution into the priming

blood to prevent the blood destruction during blood preservation. Thus we got 100% survival in the experiments of normothermic total perfusion under 30 minutes except one

case of death through technical failure. vVe think that our new type machine of

artificial heart-lung is applicable to clinical operation.

Experimental course in a typical case of total perfusion experiments during 30 minutes

is shown in Figs 9, 10 and 11. In these experiments the maximal blood pressure ranged

from 50 to 80 mm Hg. The inferior caval vein pressure and sagital sinus pressure were

both 30』 120mm I-I 0. Cerebrospinal pressure was 30～150 mm H 0.

The electrocardiographic finding was greatly affected by body position and thoracotomy

and so explaining of this finding must be deliberately done. But, in a few四 ses,P・

increasing, S-T depression and T-inverse were seen during perfusion.

CLOWES mentioned that S-T depression and T-inverse on the electrocardiographic

EXTRACORPOREAL CIR CU LA TIO N

Fig. 9 Experimental course of 30 minutes total body perfusion

~ 140

120

100

80 E吋1,0IS r 60

10 t 40

s f 20

。

f.o;(a.l 5 0 "!!!ii"""'-

歯r

ー－o.rftrialp. t－叫

トーやザザ向子h←→pザザtatd何

一－－－ce何 brodp<nA.fp.

, .... _ a，’、．．．．．．．．

Lス・：：...：－、、 ..... ~’C プ－－－ー ←二7二二・2

0 ↑

院叩 on

、．‘ 、、、．ーーー－－－－『・ーー一一一一・－－ーー一－－，’＝ι

10 20 11U/rl. 20 30 0 10

pみサFig. 10 E. E.G. in a case of 30 minutes

to ta I body perfusion

Fig. 11 E. C. G. in a case of 30 minut問

total body perfusion

号ニ、／十＼ん、戸い〆阿川

Ju.~a

P吋“い/O制札

;':t!A 25皿血

~~rr

向~－ 11(-Jl戸！戸！戸！戸J〆1戸門戸ω

10 m.Ui.

ス；；乙μ戸川川〆rf1

413

才ム川川川ρρ~~lfrowr J「ヘザムホザvJV'わ＼仇

I ~叫

finding were noticed, if blood pressure went down under 60 mm Hg. We observed

similar phenomena in our experiments, but many of these returned to normal with the

lapse of time by keeping the blood pressure with the adequate transfusion after perfusion.

Severe low voltage, arrythmia, and conduct disturbances could not be seen in the elect-

rocardiographic五nding.Bradycardia seems to be partly due to the fall of the temperature

414 日本外科宝函第31巻第3号

of cardiac muscle by thoracotomy or extracorporeal circulation.

Sometimes, E. E.G. showed temporarily slow waves by the ether anesthesia. But,

in almost all cases, E. E.G. showed no changes except in the case of severe unbalance of

in-and out岨 fl.ow. In the case of shock after perfusion slow waves and low voltage were

observed.

HoDGEs15> et al. mentioned that E. E G. is an accurate index of cerebral function

and the brain is a sensitive mirror of abnomalities due to hypoxia, acidosis and other

aberrations during total body perfusion.

CREECH6> reported that E. E.G. will be a百ected by the change of arterial blood

pressure or bloα1 fl.ow in brain. SAEGUSA29'30> observed that E. E.G. was affected by

change of blood pressure rather than blood fl.ow in brain.

In any case, E. E.G. will be important as an indicator of cerebral function during

and after perfusion. There were no abnormal changes on the physiological examination

which was described previously, during the total perfusion under 30 minutes, which was

our last experiment. It is compatible with the histological examinations desc:ribed below.

CHAPTER III. SUMMARY OF EXPERIMENT AL COURSE

We have improved the artificial heart-lung apparatus used by T. 0GATA23.w, J. TAKEDA45>, A. NoNOYAMA22>, Y. lDA16> and H. SASAKI251 in various aspects, and have

gotten the good result in the survival experiments. The survival rate was 100% except

the case of technical failure in the 30 minutes total perfusion. We have investigated the

following problems in the course of these experiments

1) Blood taking method and materials of the circuit: Hemorrhagic diathesis which

occurred in the first stage of our experiments disappeared by silicone coating of the glass

and metal portions of the circuit, and by connecting the circuit with silicone gummi-tubes.

2) Admixtures to the priming blood : For the purpose of detoxication of toxins

produced by blood destruction in the arti五cial lung, polyvinylpyrrolidone solution, anti-

plasmin preparation and acid-citrate dextrose solution were added to the priming blood.

Good results were obtained from this treatment.

3) Artificial lung: Noticing that blood destruction was great in the experiments with

the artificial lung of羽TAUD-SALISBURY33・34』＞ type, we made a new type of五lmoxygenator

but could not get satisfactory result. So, in the later experiments we used the bubble

oxygenator made by SAEGUSA 23> and his coworkers, because this type of oxygenator was

exchangeable with new one in every experiments.

4) Rapid hypothermia by A-A shunt: It was concluded from our experiments that

this hypothermic procedure was not to be applied clinically to the operation of the heart

disease. However, our pulsatile pump was proved to be safe in the long time perfusion.

Besides, it is interesting from the view-point of hernodynarnics that the animals cannulated

with arterial cannula into the right carotid artery all survived, although the animals

cannulated into the left side all died in the earlier perioq of postperfusion.

5) Hemostatic method : In the experiments of total perfusion accompanying tho-

racotomy, animals died from hemothorax in spite of the absence of coagulation failure in

the earlier stage. This was prevented by electrocoagulation and strict mass ligation.

415 EXTRACORPOREAL CIRCULATION

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changes observed were the circulatory distur-

mainly as acute congestive picture which was

CHAPTER IV.

Liver (Table 5) : The most eminent

bances which were histologically expressed

416 日本外科宝函第31巻第3号

most distinct in the liver among all the organs investigated. That is, the dilatation of

hepatic veins and sinusoides with a gradient from the central vein toward the lobule and

portal ar回 wasusually found. In severe cases, compressed basophilic hepatic cell plates

and intracellular vacuoles were observed in the central ar回 oflobule, and in the most

severe伺 S回 centralhemorrhage was observed, accompanying the rupture of central veins.

SH6Tu4°> described similar pictures in his experiments of the extracorporeal circulation.

On the other hand, it was expressed by SURUGA 44l that these changes were also

observed in the experimental surgical shock. And there has been much argument about

the relation between the changes observed in the liver of cardiac congestion and those of

circulatory shock27・42l. In our experiments some animals died from severe cardiac conges-

tion, and others from circulatory shock, and in both cas田， congestivepicture was observed

histologically. In order to show these facts, the author would like to discuss more fully

the hemorrhagic cases.

Severe circulatory shock which was caused by the toxin produced in the artificial

lung (WAUD・SALISBURYtype) was theαuse of death in the animal of No. 10 (Photo. 1).

From acute cardiac failure the animal died two hours after perfusion (rapid hypothermia

by A-A shunt) in the case of No. 16. Circulatory shock which resulted from blood

destruction by hyperthermia over 45°C in the blood temperature regulator, was the αuse

of death in the回 se of no. 23. Severe cong田 tionwas produced by filarial embolism in

the pulmonary ostium in the回 seof No. 35 (Photo. 5). In the case of No. 43 marked

unbalance between in-and out-flow which was caused by falling of the venous cannula

and returded reconstruction of extracorporeal circulation, was followed by severe circula-

tory disturbance.

On the facts above mentioned, each四 sehad its回 useof severe circulatory distur-

bances which were fatal to the animals. So, it might be concluded that the central

hemorrhage which was observed histologically in these cases was the proof of severity of

the circulatory disturbances.

However, hemorrhages without severe congestive changes were observed in some

cas白・ Central congestive picture was not so intense and rupture of central veins was not

proved in the国 sesof No. 4, No. 5 and No. 6, although hemorrhage was observed in

the liver. In these cases hemorrhage was not found in the central area, but only in the Glisson’s 油田th. SASAKI35J also described the same finding in his investigation. In these

白 S田 severehemorrhage was proved in other organs, namely spleen (Photo. 7), kidney

and lung (Photo. 20), so it might be considered that hemorrhagic diathesis which was

produced by blood destruction in the blood taking bottle and extracorporeal circuit, caused

hemorrhage in these cases, though it was di伍cultto explain why hemorrhage was observed

only in the Glisson、s曲目th.

The experiment No. 13 was the case of miliary infarction caused by fibrin clot

embolism (Photo. 4). In this case, bleeding was observed in miliary necrotic foci and

in its neighbouring area, and hemorrhagic diathesis and severe circulatory disturbances

were not seen clinically. Macroscopic infarction of the kidney accompanying hemorrhage

was observed in the same case (Photo. 12 and 13).

Since there were found only a few erythrocytes in the intercellular space in the cases

EXTRACORPOREAL CIRCULATION 417

of No. 12 and No. 19, hemorrhage might not have serious signi五cancein these cases.

Moderate or marked congestive pictures without hemorrhage were always found in

the dead cases, more markedly in the hypothermic group, These changes, it might be

considered, were produced from various 回 uses during various periods of postperfusion,

but did not always bring fatal e旺ectson the animals,

Judging from the fact that even in survivor cases, slight congestive changes were

often observed, circulatory disturbances owing to the extracorporeal circulation were pro-

bably produced in all田 sesduring postperfusion periods with various degrees Other factors,

namely anoxia, bleeding from wounds, lung complication and so on were added to thes己

disturbances : some of the animals endured, it might be supposed, while others succumbed

to circulatory disturbances or the added factors, so that postoperative treatment of these

circulatory disturbances had a gr回 tsigni五canceto the survivor of animals.

Compressed basophilic hepatic cell plate and intracellular vacuoles were both observed

in the central 紅白 of lobule, and they ran parallel with severity of the circulatory

disturbances. Intracellular vacuoles (Photo. 3) might be identical with hydropic or watery

degeneration, which was described by some authors to be caused by anoxia, intoxication

or rise of sinusoidal pressure and disappeared rapily when environment recovered normal

2・m. In the survivor cases, these vacuoles were not found.

Hemorrhagic necrosis were observed in the central area of lobule of the case No, 35

(Photo. 5), which died from severe congestion caused by filarial embolism in the pul-

monary ostrnm.

In the case of No. 13, miliary necrotic foci due to small emboli were scattered in

the liver parenchym (Photo. 4), and in the cytoplasms of neighbouring area of these

foci were proved lipoid granules by Sudan III stain. Large macroscopic infarction in the

kidney was observed in the same case, but evidence of infarction in other organs, namely

brain, heart, and lung was not proved probably because of partial perfusion in which the

pump sent the blood mainly into the abdominal organs, The material of emboli was

probably五brinclot which was not proved histologically but found in ~he artificial lung

(our film oxygenator). The filter in arterial line of extracorporeal circulation was not

used in this回 se. Hemosiderosis due to hemolysis was proved only in severalαses but

it was not considered to be so serious.

Eventually, main findings in the liver were hemorrhage, congestive picture, infarction,

and cellular degeneration, namely compressed hepatic cell plate and intracellular vacuoles.

Many of the causes of these changes were removed by our improvement of the circuit,

blood taking method and perfusion technic, so in the recent experiments histological

changes became slight and small, and even these changes were all reversible (Photo. 6) .

Spleen (Table 6) : Histological findings in the spleen were mainly circulatory distur-

bances as in the liver, but those severity was slightly milder than the liver. Acute

central congestion with dilatation of sinusoides20i was generally observed. Severe congestion

and hemorrhage were also observed in the case of No. 35, which died from五larialembolism. Slight atrophy of splenic follicles was observed in some of the dead cases.

Splenitis accompanying infiltration of polymorphnuclear leucocytes was observed in some

cases, especially in the hypothermic group, but severity was generally slight in each cases

第3号第31巻日本外科宝函418

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(Photo. 8). Slight increase of reticulum cells was found in several cases, but its sig-ni五cancewas not clear. Hemosiderosis was seen in some cases, especially in survivor cases, though it was slight (Photo. 9) .

Kidney (Table 7) : The marked change in the

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kidney was also congestion which

EXTRACORPOREAL CIRCULATION 419

was generally seen in the border region between the cortex and medulla, though its

severity was more slight than that of the liver and spleen. Severity of congestion ran

parallel with that of the liver, but in the hypothermic group congestion was not observed

generally.

Hemorrhagic cas白 werealmost coincident with those of the liver, but its severity

was considerably moderate. Hemorrhage was observed in the cases of hemorrhagic dia-

thesis (No. 4, 5 and 6), infarction (No. 13, Photos. 12 and 13), postperfusion shock

(No. 10) and filarial embolism (No. 35, Photos. 10 and 11).

Changes of gl0merulus and BowMAN’s capsule were generally moderate, and di百ere-

nces between the survivor and d田 d cases were not seen. Protein-like substances were

observed in the capsular space and tubules in some cas田. Erythγocytes in the capsular

space were observed in the回 seof extreme congestion due to filarial embolism.

Cloudy swelling, granular degeneration and desquamation of the tubular epithelium

were generally slight and probably reversible except the severe hemorrhagic cas白. Dege-

neration of tubular cells of the lower nephrone and eosinophilic or protein-like cylinders

in the tubules were more marked in the hemorrhagic四 seof group I (A) . These findings

might be concerned with the hemorrhagic diathesis caused by blood destruction.

Moderate degeneration of the tubular epithelium including one 田 se of hyaline

degeneration was observed in almost all 四 sesof hypnthermic group. These changes

and ischemic pictures already mentioned were characteristic in this group.

In the case of No. 13, large macroscopic infarction in the shape of triangle was

found. This was probably caused by fibrin clot embolism in the larger branch of renal

artery (Photo. 12 and 13).

Although dilatation of tubular lumina was seen in many of both survivor and dead

cases, it was considered as the complication following anesthesia and surgical operation.

Moreover, round cell in五ltrationwas observed in some cases, but this was probably

caused by parasites which were detected in one case.

Adrenal gland (Table 8) : Circulatory disturbances were slight in the specimen of

hematoxilin eosin stain, and hemorrhage was not observed in any case.

Histological findings in the specimen of Sudan III stain were demonstrated in Table

8. Generally, these changes should be considered as stress『 response36>. The main histo-

logical change was the reduction of lipoid granules in each layer, especially in fascicular

layer (Photo. 15). In the cases of marked lipoid reduction, large vacuoles were observed

in the cell and the cell itself became larger than normal. Comparing the deadαses

with the survivor, more marked lipoid reduction was found in the former, but more

marked vacuoles existed in the latter. The border part between the glomerular and the

fascicular layer was recognized clearly in the normal contrast animals and almost all dead

cases, but became obs:::ure in many survived cases owing to the proliferation of cell plate

from the glomerular layer to the fascicular layer. Regeneration of the lipoid granules

took place more widely in the回 sesof 4 and 8 days after perfusion than in the case of

2 days. The case of 8 days was almost normal histologically except some disarrangement

of cell plates (Photo. 15 and 16).

In the hypothermic group the most characteristic picture was the minimal histological

第 3号第31巻日本外科宝函420

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421 EXTRACORPOREAL CIRCULATION

Table 11 Brain

(Degeneration of ganglion

cells) (Niss！’s stainJ

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同 I35土土土 12己 I43一一土 3 c ・-

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I 33一 一 一一一一＋一一＋ 48 ' 36一一一一一一一一一一 4837一一一 一一一一ー一一 4839一 一 一一一一＋一一＋ 192 42一＋一一一一＋一一＋ 96 44一一一一一一＋一一＋ 48

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of left ventricle, especially papillar muscle. Histological specimens were taken from the

apical region of left and right ventricle in the present investigation. Results of the

investigation were shown in Table 9. Except two cases with small hemorrhagic foci

422 日本外科宝函第31巻第3号

(Photo. 18), slight congestion and minimal degeneration of heart muscle were found in

some回 ses. Vacuole degeneration, myocardial fragmentation, edema of interstitium and

round cell in五ltrationwere all not detected. Eventually, the fatal lesions were not observed

at all in the cardiac muscle.

Lung (Table 10) : Miscellaneous changes were found in the lung. The majority

of these were probably arisen from ether anesthesia and thoracotomy. Congestion and

moderate hemorrhage of many cases might be concerned with ether anesthesia21), while

local emphysema and atelectasis with thoracotomy.

Marked hemorrhage in the alveoli and bronchioles was observed in the四 seof No.

6 which showed hemorrhagic diathesis clinically (Photo. 20). Histological findings of

pulmonary edema (Photo. 21) in the C勾seof No. 25 coincided with the clinical picture.

At all, hemorrhagic diathesis and pulmonary edema were only caused by extracor-

poreal circulation and both changes disappeared in the last experiments.

Brain (Table 11) : It goes without saying that the brain is most important in the

whole body. Furthermore, it is the most sensible organ to anoxia. The functional

depression and the morphological lesion of brain caused by extracorporeal circulation have

been studied by many investigators, and innumerable studies have been made on th慨problems from various points of view8 25札 37・4L43・48.50・52).

In our experiments, abnormal changes of electroencephalogram and cerebrospinal

pressure were observed during and l、2hours after the extracorporeal circulation. In

order to clarify the relation between clinical pictures and morphological changes, the

author examined the brain of the animals histologically. Histological specimens were

五xedin pure alcohol immediately after autopsy, then through the celloiden embedding

were stained by hematoxilin eosin stain and NrssL’s stain. The author mainly investi-

gated circulatory disturbances, edema of white matter and degeneration of the ganglion

cells of cerebral cortex, AMMON’s horn and cerebellum.

As for the circulatory disturbances, slight congestive changes were only observed.

Bleeding, red softening and white softening which were described by H. SA131> were not

observed in our cases. Enlarging of VmcHow-RoBIN’s space was observed in someαses,

but it is not veri五edthat these changes express the brain edema because of the lack of

macroscopic findings of edema in each case. In short, brain edema with clinical signifi圃

cance was not found in our experiments.

Findings of NrssL’s stained specimens were shown in Table 11. We must take a

prudent attitude for the decision of degenerative changes of NrssL bodies because it is

delicate and so must take considerable time for the occurrence of degenerative change

of ganglion cells. In the present investigation, degenerative changes were observed in

survivor cases rather than deadαses probably because of the above mentioned reason.

However, degrees of degenerative changes were generally slight.

In the cases of 30 minutes perfusion, the changes were more severe in the case of

4 days after perfusion (Photo. 22, 23 and 24) than in the case of 2 days, but the

changes were more slight in the case of 8 days than of the 4 days. By these findings

it may he considered that these degenerative changes were reversible in the post-perfusion course.

EXTRACURPORE人LCIRCULATION 423

CHAPTER V. SUMMARY OF HISTOLOGICAL FINDINGS

1) Circulatory disturbances: The most eminent changes throughout all investigated

organs were the circulatory disturbances which were histologically expressed mainly as

acute congestive picture. In cases of severe congestive picture, hemorrhage was observed

in the liver, spleen and kidney. As the causes of these severe changes, failures of

perfusion technic，副aria! embolism in the pulmonary ostium, acute cardiac failure and

circulatory shock due to the blood destruction were considered. The blood destruction

was minimized by the improvement of the arti五ciallung, blood taking method and mate-

rials of extracorporeal circuit, so that circulatory shock caused by the blood destruction

disappeared in the later experiments. Furthermore, hemorrhagic diathesis observed in

the dead cases of group I. (A) disappeared by our improvements mentioned above.

2) Anoxic changes : The severity of anoxic changes ran almost parallel with that

of circulatory disturbances in each case. Necrotic changes were observed only in the

focus of infarction and in the site of severe hemorrhage. Anoxic changes in the brain

were also reversible in the post-perfusion course.

3) Embolism : The embolism by fibrin clot, antifoam agent, air bubble and other

foreign particles was written in many literature, but throughout the our experiments

pictures of infarction in the liver and kidney were found in only one experiment without

the filter in the circuit. Any infarction was not observed in the recent experiments with

our improved circuit.

4) Hemolysis ・ In the histological investigation, hemolysis might 民 expressedas

hemosiderosis and lower nephrone nephrosis. In the present investigation, hemosiderosis

found in organs were all of slight degree, and degeneration of tubular cells as well as

intratubular cylinder in the lower nephrone were found only in the dead cases of group

I. (A). In the other cases, histological changes due to hemolysis were considerably slight.

5) Stress-response: Reduction of lipoid granules of the adrenal cortex were obser-

ved, however process of recovery from stress response was evident in the survivor cases.

6) Pulmonary complications : As for the complications due to the extracorporeal

circulation, pulmonary edema was proved in one case, but none of them were observed

in the recent四 ses.

7) Rapid hypothermia by A-A shunt : The most important負ndingis the scarcity

of lipoid reduction in the adrenal cortex in this group.

SUM恥rIARYAND CONCLUSION

We succeeded in the survival experiments of extra corporeal circulation using the

pulsatile pump produced by 0GA TA and his co-workers, improving the circuit, artificial

lung, blood taking method etc.

The survival rate in the 30 minutes complete perfusion was 100% with the exception of technical failure.

With the progress of experiments，五ndingsof histology and other observations were improved gradually.

In the last stage of From our experiments, it was concluded that our artificial heart

lung machine became usable and safe clinically from the view『 pointof histology.

424 日本外科宝函第31巻第3号

The author wishes to sincere gratitude to Dr. Y. H1KASA, the lecturer of our clinic, for his valuable guidance

and encouragement in the course of present experiment. The author is also grateful to his coworkers, D日.J.

TAKEDA, A. NoNOYAMA, H. SASAKI, H. YAMAZAKI, K. ABE and K. TsusHIMI for their kind as_sistaiice.

REFERENCES

I) Abe, K. : Experimental Studies on Bleeding Diathesis not Uncommonly Accompnied with Extracor・

poreal Circulation. Arch. Jap. Chirur., 31, , 1962.

2) Anlyan, W. G., et al. : A Study of Liver Damage Following Induced Hypotension. Surg., 26, 375,

1954. 3) Brown, Jr. J. W., et al目： Experimental and Clinical Studies of Controlled Hypothermia Rapidly

Produced and Corrected by a Blood Heat Exchanger During Extracorporeal Circulation. J. Thor.

Surg. 36, 497, 1958.

4) Clowes, Jr. G. H. A., W. E. Neville : The Membrane Oxygenator. In Allen, J. G., ed. : Extracor-

poreal Circulation. Spring品eld,Ill. Charles C. Thomas, 1960. p. 81.

5) Clowes, Jr. G. H. A., et al. : Factors Contributing to Success or Failure in the Use of a Pump司

oxygenator for Complete By-pass of the Heart and Lungs. Experimental and Clinical. Surg. 36,

557, 1951

6) Creech, Jr. et al. : Cerebral Blood Flow during Extracorporeal Circulation. Surg. Forum. 8, 510,

1957.

7) Dennis, C., K. E. Karlson : The Multiple Screen Disc Oxygenator. In Allen, J. G., ed. : Extracor-

poreal Circulation. Spring五eld,Ill., Charles C. Thomas, 1960, p. 69.

8) Halley M. M .. K. Reemotsma, 0. Creech : Cerebral Blood Flow, Metabolism and Brain Volume in

Extracorporeal Circulation. J. Thor. Surg. 36, 506, 1958.

9) Hikasa, Y. et al. : Significance of Fat Nutrition I (written in Japanese). Surgical Diagnosis and

Treatment, 1. 332, 1959.

JO) Hikasa, Y. et al. : Signi品canceof Fat Nutrition II. Ibid .. 2, 117, 1960.

11) Hikasa, Y. et al. : Signi五canceof Fat Nutrition lff. Ibid,. 2, 253, 1960.

12) Hikasa, Y. et al. : Signi品canceof Fat Nutrition IV. Ibid., 2, 386, 1960.

13) Hikasa, Y. et al. : Significance of Fat Nutrition V. Ibid .. 2, 648, 1960.

14) Hikasa, Y. et al. : Significance of Fat Nutrition VI. Ibid., 2. 931, 1960.

15) Hodges, P. C目， etal. The Effects of Total Cardiopulmonary By-pass Procedures upon Cerebral

Function Evaluated by Electroencephalogram and a Blood Brain Barrier Test A Clinical and

Experimental Investigation. In Allen, J. G目 ed: extracorporeal Circulation. Springfield, Ill・， Charles

C. Thomas, 1960. p. 279.

16) Ida, Y.・ExperimentalStudies on Carbohydrate Metabolism during Heart-lung Bypass, with Special

Reference to a Comparison of Pulsatile Flow with Non-pulsatile Flow. Arch. Jap. Chirur., 31, 181, 1962.

17) Kirklin, J. 可へん R. A. Theye & R. T. Patrick : The Stationary Vertical Screen Oxygenator In

Allen, J. G .. ed. : Extracorporeal CircしlationSpring品eld，日I.,Charles C. Thomas, 1960. p. 57.

18) Kobayashi, Ch. : Studies on Extracorporeal Circulation, with Special Reference to Observation of

Cerebral Hemodynamics uncer Extracorporeal Circulation Using Mechanical Heart and Lung. J. ].

A. T. S. 8. 942, 1960.

19) Kuwana, K.: Experimental and Clinical Studies on Profound Hypothermia. Arch. Arch. Jap. Chirur.

31. 158, 1962.

20) Mi,・achi. T. ed. : Clinical Histopathology (in Japanese). Tiiky, Kyorin Shoten. 1956:

21) Nakajima J.:E任ectsof Ether, Cyclopropane, Nitrous Oxide and Fluothane upon the Lung Alveoli.

Arch. Jap目 Chirur.29, 39, 1960.

22) Nonoyama, A.: Hemodynamic Studies on Extracorporeal Circulation with Pulsatile and Non-pulsatile

Blood Flows. Arch. Jap. Chirur., 29, 1381, 1960.

23) Ogata, T. et al. : A Comparative Study on the Effectiveness of Pulsatile and Non-pulsatile Blood

Flow in Extracorporeal Circulation. Arch. Jap. Chirur., 29, 59, 1960.

24) Ogata, T. et al. : Experimental Studie' on the Extracorp<》realCirculation by Use of Our Pulsatile

Arterial Pump. Lung (in Japanese), 6, 381, 1959.

25) Patrick, R. T. et al. : The Effects of Extracorporeal Circulation on the Brain. In Allen, J. G. ed.:

Extracorporeal Circulation. Spring品eld,Ill., Charles C. Thomas, 1960. p. 272.

EXTRACORPOREAL CIRCULATION 425

26) Piwnica, A., M. Weiss. C. Lenfant, Ch. Dubost : Circulatory Arr引 tand Deep Hypothermia Induced

with a Pump Oxygenator System and a Heatexchanger. J. Cardiova,c. Surg. 1, 71, 1960.

27) Popper, H. 8.: F. Schaffer: Liver, Structure and Functi9n. N. Y .. Mc Graw-Hill Book Comp. Inc.,

1957.

28) Saegusa et al. : Open Heart Surgery with the Aid of Rapid Cooling Method Employing Pump-

oxygenator. Jap. J. Thor. Surg. I( 527, 1961.

29) Saegusa et al. : Electroencephalogram during Extracorporeal Circulation with the Aid of Pump-

oxygenator I (in Japanese). Jap. J. Thor. Surg .. 12, 111, 1959.

30) Saegusa et al. : Electroencephalogram during Extracorporeal Circulation with the Aid of Pump-

oxygenator II. Ibid .. 13, 718, 1960.

31) Sai, H. : Studies on Histological Changes of the Brain Tissue in Utilizing the Artificial Heart-

lung Apparatus. J. J. A. T. S .. 5, 1187, 1957.

32) Saito, H. : Experimental and Clinical Studies on Profound Hypothermi11 ・ ・ ・ Prevention from

Ventricular Fbrillation ・・-. Arch. Jap. Chirur., 31, 132, 1962.

33) Salisbury, P. F. : Extracorporel Circulation as an Aid to Cardiac Surgery. Handbuch der Thoraxc-

hirurgie, Springer-Verlag Berlin Goettingen Heiderberg, 1958.

34) Salisbury, P. F. et al. : Physiological Factors in the Use of the Pump-oxygenator. Trans. Amer.

Artif. Int. Org., 1, 68, 1955.

35) Sasaki, H. : Experimental Study on H日topathological Changes in the Liver and Kidney during

Extracorporeal Circulation, with a Special Reference to a Comparison of Pulsatile Flow with Non-

pulsatile Flow. Arch. Jap. Chirur. (to be published)

36) Sasano, N. : Pathology of Adrenal Cortex (written in Japanese). Saisin-igaku, 10, 1391, 1955.

37) Schmotzer, K. J. et al. : Evidence of Air Embolism with the Bubble 0>Cygenator. Surg. Forum., 8, 418, 1957.

38) Shirotani, H. et al. : An appraisal of Essential Fatty Acid in H、pothermia・・・Fromits fundamental

experiments to clinical application・・・I, Jap. J. Anesth., 10, 8, 1961.

39) Shirotani, H. et al.: An Appraisal of Essential Fatty Acid in Hypothermia・・・From its fundamental

experiments to clinical applicatiion・・・II, Ibid., 10, 92, 1961.

40) Shotu, A. : Studies on the Artificial Heart-lung System・・ ・with Special References to the Influence・against the Individuals and the Causes of Death. J. J. A. T. S., 6, 745, 1958.

41) Silverstein, A., et al. : E任ectson the Brain of Extracorporeal Circulation in Open Heart Surgery

ー・ANeurologic, Electroencencephalographic, psychiatric and Neuropathologic Study. Neurology, 10, 987, 1960.

42) Spellberg, M. A. : The Liver in Shock and Anemia. Di司 asesof the Liver, New York, Crune &

Stratton, 1954, p. 504.

43) Sunada, T.: Undetected Brain Damage in Extracorporeal Circulation・・・Especially with Bubble Type

Artificial Lung (in Japanese). Jap. J. Thor. Surg., 12, 305, 1959.

44) Suruga, K. : Histological Studies on the Secondary Shock (in Japanese). J. J. S. S., 51, 142, 1950.

45) Takeda, J. : Experimental Studies on Peripheral Circulation during Extracorporeal Circulation, with a Special Reference to a Comparison of Pulsatile Flow with Non-pulsatile Flow. Arch. Jap. Chirur., 29, 1407, 1960.

46) Tomioka, Y. : Experimental Studies on Hypothermia, Arch. Jap. Chirur., 30, 17, 1961.

47) Trowell, 0. A. : The Experimental Production of Watery Vacuolation of the Liver. J. Physiol. 105, 268, 1946.

48) Urabe, M. : Studies on Extracorporeal Circulation Aming at Direct-vision Open Heart Surgery (in

Japanese), Jap. J. Thor. Surg., 12. 300, 1959.

49) Waud, R. A. : The Use of the Artificial Heart-lung in Pharmacology. Trans. Amer. Artif. Int.

Org .. 1, 68, 1955.

50) Willman, V. L. et al. : Air Embolism. In Allen, J. G. ed. : Extracorporeal Circulation. Springfield,

Ill., Charles C. Thomas, 1960, p. 295.

51) Yamazaki, H. : Experimental Studies on Extracorporeal Circulation using Pump-Oxygenator with

Particular Reference to the Effect upon Blood Gas, Acid-base-balance and Carbohydrate Metabolism.

Arch. Jap. Chirur., 31, 1962.

52) Zubdi, N. et al. : Cerebral Changes during Cardiorespiratory Bypass Using the Helix Reservoir

Bubble Oxygenator. J. Surg., 37, 703, 1959.

426 日本外科宝函第31巻第3号

和文抄録

人工心肝装置を以てする体外循環の実験的研究

回路装置の改良と組織学的検索

京都大学医学部外科学教室第2講座 （指導：青柳安誠教授）

竜田憲和

複維な必臓内手術を安全に行なうためには，十分な

心血流遮断時間，或いは心停止時聞が必要である．こ

の点についてわれわれの教室の諸方p 武田，野々山，

井田，佐々木は脈動式ポンプを用いた体外循環実験を

行ない，長時間の体外循環を行なう際には脈動流を用

いた方が無脈動流を用いるよりも良好な結果が得られ

ることを証明した．しかしこれらの実験はすべて生理

実験であり動物の生存を目的とするものではなかった

ので，この装置を臨床に応用するには尚可成りの改良

を要することが予想されていた．

そこでわれわれは，この人工心肺装置を臨床的に安

全に応用するために，更に動物の生存を指標として新

しく器具改良に関して実験を行なった．まず人工肺を

用いない部分循環実験から始めてこれに成功した後，

；：.：工肺を用いた部分循環実験を行ない，更に完全体外

循環実験へと前進した．尚この間に arterio・arterial

shuntによる急速冷却法の実験をも行なった．この実

験経過中に採 lli l ；~ J 回路装置，循環装置等に種々の改

良を加えたのであるが，その主な改良点は次のような

点である．即ち

111 採血瓶及び回路内の金属及びガラス部に sil1co-

ne coatingを行ない，これを連結するピニール管を

silicone rubber管にかえることによって血液因子によ

る出血傾向を消失せしめ得た，

121 主として人工肺内部で生ずる血液破壊物質によ

る中毒現象を防止するために polyvinylpyrrolidone,

抗プラスミン剤及び川’cl-citrate-dextr"esolutionを血

液中に添加して好成績を得た．

i31 従来用いて来た Waud-Salisbury型人工肺は血

液敏裏方：著しいのでP われわれば新しく司種の film

oxrgenatorを試作した． しかし満足し得る結果が得ら

れなかったので結局東京大学三枝らの設計による二重

円高気i包~の人工肺を採用 した．

(4) また， I旬~村出血のー原因としてその関胸時の

止血i去に’て陥があったので electrocoagula ti on等を併

せ行ないこれを可及杓完全に行なうように努めた．

更にp a-a shunt』こよる急速冷却実験ではp 臨床

的にそれを応用することは出来ないとの結論に達し

たが，脈動式ポンプの安全性を証明することができ

た．

以上の実験経過を辿る閉じ試獣の生存率は向上し

遂に完全体外循環30分の実験群では，技術姐誤の 1

例を除けば100%の生存率を得るに至った．

更に，この間の経過を主として病理組織学的に追求

したがp その検索対象として肝，牌，腎，副脊p 肺，

心及び脳を選び，その際主要な所見として吟味したの

は

川循環葎碍

12）伺酸素症による退行変性

13）栓塞

(4) 溶血による変化

(5) ストレスに対する反応

(6）肺合併症

(7) その他

である．そしてこの中で試獣の主死因となった著明屯

所見は循環障碍のそれで出血死に次いでいる．而もこ

の変化は肝に最も著明に認められた．併しわれわれが

前述のように諸麗の点を改良することによって，これ

らの組織予均所見も亦漸次改善され，われわれのii!終

段階の実験である30分間完全循環群では，変化はすべ

て軽微であり尚も可逆性であることが判明した．従っ

てわれわれの人工心肺装置は最早臨床的にも安全に応

用し得る段確に立ち至ったものと考えられる．

EXTRACORPOREAL CIRCULATION 427

Photo. 1 （×60), Liver, No. 10 Severe central

congestion accompanyig hemorrhage is

observed.

Photo. 4 （×150). Liver. '.'¥o. 13 Necrosis due

to miliar embolism is珂 刊

Photo. 6 （× 150〕，Liver, ¥u. 44

Histological change is minimal.

428 日本外科宝函第31巻第3号

Photo. 7 （× 150〕， Spleen，「＼o.6 Hemorrhage

and severe hyperemia is seen in the

splenic pulpa.

Photo. 9 ( X 600), Spleen, .'¥:,,, 35

Hemosiderosis in the splenic pulpa is

observed

Photo. 11 （×150), Kidney, ~o. 35: Congestion accompanying hemorrhage is、町、nin the

border region between c< 1rtぞxand medulla.

Photo. 8 ( x 600), Spleen No. 20 :

Polymorphnuclear leucocytes are observed

in the splenic pulpa.

Photo. IO ( x 150), Kidney, No. 35 Congestion

and tubular degeneration are observed.

Photo. 12 ( x 100), Kidney, No. 13 目Necrosis

due to infarction is seen.

(right side)

EXTRACORPOREAL CIRCULATION

Photo 15 （× 100), Adrenal gland, No. 44 :

Considerable decrease of lipoid granules

1s seen.

Photo. 17 （× 100), Adrenal gland, No. 18・Histological change is minimal.

Photo. 18 （× 150), Heart, No. 9 Small

hemorrhagic lesion j, present.

429

430 日本外科宝函第31巻第3号

Photo. 19 （× 150), Heart, No. 39 ‘ Photo. 20 ( x 150), Lung, No. 6 : Congestion

No histological change is seen.

Photo. 21 （× 150), Lung, Nり 25・Intraalveolarexudate and atelectasis are seen.

Photo. 23 （×600), Ganglion cells in

hippocampus, No. 42 Picnotic

ganglion cells are present.

with hemorrhage is seen.

Photo. 22 ( x 600), PuRKINJE cells, No. 42

(N1ss1九 stain)Swollen PuRKINJE cells

are present.

Photo. 24 （× 600), Ganglion cells in cerebral

cortex, No. 42 :

Mild chromatolysis is seen.