Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
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
てコc
" - 'f,
t: 4:'. U 』τ 戸主- ~ -,o 2 E乙凶 G 9コ
ベ ロニニ=c " ー一三主 :':: Eよ f:: bl c ...c 巳 4-< :: ;:-',
" " :: Q, ' c 0 'O,l ;二てニ〉、こで,, :-::: 0 0ト
ー = ζ J九一=令.... ~ - _:;;.,二
~1 &~~( 2 包.~ @ ~ ~ ~ 」 l バ" " ~内で= ~ '"' = L二 l ~ヱ(」〈工占占ヱト£
I 4ー掛冊一一一一 15 Iー<!'. 5 *州士一一一一 12 ' ~ ~ 6 *柵+一一一一 5 : -a
~ 7一一一一+ + - 48 i ]
I 9一件一+一一一 48 I ~ "
I IOー併一一一+ - 25
:: 13ー+++一一+ - 26
巳. '
~ 1 1ー榊ー+一一一 48占 12一一一一+一一 48
114ー++一一件ー 4815一一一一一一- 48
16一件一一土一一 2 17ー士一一一一一 3 18 - +士一士一一 5 19ー十一一+-- 5 20一一一+#+一 7
I ペコ21ー土ー++一- 48 ! ~
22一件一+一一- 48 ~ f.
23一冊+一一一一 2 24一件十一一一一 3 25一件ー十一一一 5 26ー+++一一一一 0 31ー榊一一一+ー 5 32一件一一一一一 2 35 -州+一一一件 1243一件一一一一一 3
Spleen Table 6 Liver
(
ωtNECZ
)
kfユご
τニ山=H
司円
E==
zコ』」記一EE』月一誌にむ一。門戸=’門
==ニ己主zuu一》し一=
5ご〉
rzvbむZ
む一吉一
ι
=ivuuニC己むよ℃LUJJL』且戸』ご
f)
よ
22むで
ZCEむエ
==ニυbw』己目
、
JU一uコアコ=【閉山
口むニー心はにCUム戸一吉U4出
JFEZ己一同)
,
Eωン一
EHEω)
h
よtdlw戸一ι〆己ciZ同一川)
uwUよとご
Eωヱ
{
ロ
む
〉
一
EHZω’)
,
=
EH戸HUE-」む〔】リ,
h
川向
己コC1M山)
Table 5
i 4一件特件特一一士一件 1<t I sー+++++++一一一一件 1』 I 6一株+++++一一十一++己 l 一一一一一一一一:l I ' F 巴
2 I 7一一一一+一一一一+ 48 I ~ F「 1
二三二三二土=・=一一一竺 rl10 *一冊+++一一件ー俳 25 : ~
I "-' 13 + 一 冊 - tit+一件+仲 26 I勺
11一一一一+ 一一一一一 48 Iヲ12士一土+一一一一一+ 48 ! .~ 14一一+一件一一一一土 48 ' 1: 15一一冊+十 一一一一一 48 i 三
16冊一朴+十冊一件特- * 2 17一一件怖件一一ーー+ 3 I七
18一一件**一一一ー- 5 : ::s 19土一件件件 ー+一一冊 5 '勺
20一一+十件++一一一一土 7 I
21一一一一一一一一一一 48 ! ~ 22一一一一土一一一一土 48 ~
f,
23 * + *十件耕一一++一時24一一+一件一一一一土25一 一 + 一 件一一一一土26一一件ー掛一一一一件31 - - *一件一 一 一 一 件32一一件一件一一一一件
同 I35 #十- tit件冊一一* + * 1 ιI 43 +十一冊**ーー一一土ロ l
~ I 30一一件件特一一一一一 433一一++++一一一一+ 4 36一一土土士一一一一一 437一一+++ー土一一+ 4 39一一土土士一+一一一 1942一一件件特一一一一一 944一一件特十一一一一一 4
セコむ一ν
てコOJ 〉
〉』
吋-f.
t-己-ν
一νmvjw℃
白山[
ιロ20
υ][己主己乙
υ][品ロ
EO
一)
Cω七
-ru[)
七bkJtごコ♂
888868
44-’44告
4・qua4
++朴一一一
一一一一一+
一+一一一一
一一一一+一
一一一一一一
+土一土一一
一一一一一一
日U
『υ戸りヴ’nLAせ
quqυquqυ44a4
[
己~
r 」
む〆-h/』【戸小山
HISTOLOGICAL FINDINGS
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
可コ山〉
と
I ~
(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
Kideney
c
"' 也J ヅ:. ..
Z三三 五 ~ ~ ] 』 -D む E - '"'
ー ロ.§ E ~ 1岩戸 .s ·~ l'l°’E () H 丘「一~·~一一「ーーー とι= c" -ー山 ...
'"' --- ・- v lo-< 1--o - ~ - w .... 円 口 口 E ヨ H 0.
古5 3ーュ 2 ·~ ・B E長官 E? ~ ~ 8 ::: ぷ 話 坦 5~ §若主 8 g 。 ぷ ヨヨ.:: iil c - ;;; G 』 E
5 「戸削む; Z 事~野川れをて~ s 3 .;: " c. i':':主 -0 :;; L ’U ~三:2 ~ ;:: Cl'~
巳' E七ニ ロ コ 』 穴 と 回 三 ω 記とー巳 6・ 出 む 0
,1 1 ! ~ i ! 1 ~ ! i ~ i I ! f f 1 ! ! H '""I w ::c:φ 回以~ u凶 Lυυ () ::c:同仏 w凶占ド」d
I 4 + +一+一一++一件一++++ー 1s I司
<i: I s +一一+一一一一一件ー+++一一 12 : i3 H I 6件++一一一++件件一+++一一 5 I匂
ι
主 7ー++一一一一一+土一件一一一一 48 I~ -i 8一冊+一一一一一一+一一+一一一 48 I ~
1 泊
I 10骨骨骨一一一一一一+ー+一一一一 25 I司
巴I13 + + +一一++一一+一件一一一+ 26 I屯c. -一一一一一一一一 • 日 11ー+一+一一一一一一一+一一一一 48 I 1l 0 12ー+土一一一一+一一一件一一一一 48 I ~
I 14ー++一一一一一一一一件一一一一 48 I i: I 15ー++一+一一一一+一件一一一一 48 I ~
I 16ー+一一一一+++一一件+一一一 2 I 17一一一一一一一+一+一件一一一一 3
υI 18一一一一一一一件++一件+一一一 5 H I 19ー+一一+一一一一+一一一一一一 5
号 20一一一一土一一一一++一一一一一 7
0 一一一一一一一 一。I21一一+一一一一一一一一++一一一 48 I~ I 22ー+一一一一+一一+一件一一一一 48 I ~
' "' 23一時一一+一一+一+ - tit一一一一 2 I 24ー++一+一一一一一一十一一一一 3 25一+一一一一一一一一一+一一一一 5 26一一一一一一一一一一一件一+一一 0 31一件一一+一一一一一一件ー+一一 5 32一件士一一一一一一一一一+一一一 2 35十件一一一士一一僻伸一一一一一一 1243ー+一一一一一一+一一+一一一一 3
30一件+一一一一+一一一冊一一一一 4833ー+一一一一一一一一一++一一一 4836 -一一一一一+一一++-+++ー一一 4837ー+一一一一+一一+ー#+一一『 4839ー+一一一一一一一一一冊一一一一 19242ー+一一一一一一+一一一一一一一 9644ー+一一一一一一一+一一一一一一 48
目
umwω唱
市》
RW同》
Table 7
】同己コ《MH’)
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
一宮〉2223名一BEES-官名一3E25
古毛
一lili--
11111111111Lilli--ll!41111111「lilll11111Lilli--
1111lili--
C4E52Eし日目立~ム
ω日
目
一
必
必
一
お
お
-
MZ一27
3
5
5
7
一必必↑
235052mM3
ち口05EωE凶ωQ一一一一士一一一一一一一士一一一一一一一
ECZE出口。υ一一+一+一一一一一一一+一一一一一一一
ω同盟tEEω国一一+一一一一一一一一一一一一一一一一-
6口舌ω日ロω且H4一
7
9
一0
3
一1245一67890一1
2
れLP
一唱B
--ti
一TiT4Ti
’A一’A唱A唱AτA今L
一行ノ臼内L
ヨ
一
回EEO
一llυHEZ占
Table 9
内回ロ20
Adrenal gland
(
FFMコミよ)
hm〈-CHコ勾
CH司EEC-
g℃包
EC』』戸一EE一宮EH一
23HU一色
hv己ちいれWCωHU出一
、
ωω一DロU団〉tMC一==rwU戸HHZH一
』ωヘ円何一一ωω一口EE回目ν=江同一』C主ZEω(]
A
一
=一zυニω尚
一
戸
一
色
E
H
d
眠、
BAP
--』亡邑A
Z
ωω一C2ud〉』偲一ロ=uυ2HZH
Ehd〕一一z一=己目』国司三二回DωE』Uω凸一
』戸d
一コυHUmロL
-
z
一
品
2
H
〈
kP12亡包内ヱ
-MU〉己一』三一コυ-υぬd
』一
℃己司』Ed一・石口ωω〉乙ω』
ω口一
7u-uhq凶一
Rw-52uπ〉』MW一ョ一一心υCMHZH
む一ロロ己冊目】目。ι-一』=自EhdQ
Ehc二〉
よ
ら
玉
〈
己苛一-ごしE=一山)↑ン戸一ιE亡
krz
-CZ#己
ω戸何回』じ品日
ω
ιコC』
O
一同〈
Table 8
! 16一一一一 clear一一士一一一一一-u ! 18一一一一 clear一一+一一一士一一二119一一一一 clear一一+土一一一一一コ| 一一一一一一一一一一一一一一一一一一一一一一一一一一ー一一~ I 21一一一一 clear一一++一一一一一
I 22一一一- clear一一件+一一一一一
23一一一一 clear一一件一一一士一一24一一土- clearー++一一++一一25一一+ - clearー+僻一一+++一一26一一+ -clear一+ト冊一一十件一一31一一一一 clear-一件一一+一一一32一一士一 clearー+士一一+士一一35一一廿- clear +一件一一一僻一一
I 43一一+ - J~:r 一+士一一一+一一ιl一一一一一ー一一一一一 一一一一一一一←一一一 一一一一一一一一一一一一一一一一一一一-2 I 3o一一+ - -~~OtT +一件土+一一一一 48 I 。! 二一 I
33一一+ - cY~:r +ー+士一一土一一 48 I 戸己
37一一件- cl~atr +ー#件+一+ー+ 48 ~ 39一一一一 clear- +土+一一土一一 192 i ;
42一一+-;ζT一 一 + 一 一 一 土 一 + 96 I』
44一一俳- cl~:r 一一件一一一+一+ 48 i
change apparently distinguishable from the normothermic group (Photo. 17) .
Heart (Table 9) : It has been described by some authors that the changes which
are seen in anemic cardiac muscle, are often found at the subendocardial muscular layer
てコω 〉同
〉』
= "'
48
10ー+土- clear一一冊一一一+一一
13一一件- cl1ヰ-+州掛一一件+一
11一一土- cl~atr + ー 州 ト ー ト ー 48 11) 12一一土- cl~:r +一冊+一一士一+ 48 i .E 14一一+ -clear - --t十件+一士一一 48 I :;:; 15一一一一 clear一一件一一一土一一 48 I
i]
日)
cuw
-v
9一一+ -clear -一十一一一+一一
25
26
凶』己主己。
一一一一一一土一
+一一一一一一一
一一一一一一一一
34561A253
22223334
力むと〉』口小
つ白RdFUoo
aH1
48
23505223
ー 一
ヲ
zzhEω
一888268
一an--an--an--内対M
《
udan唯
一一一一一
↑+一一一
一一一一一
nvqu氏V円
J
9dqυqυつd
一一+一+一
つbA宅
A4・aハヨ
同《凶コ
20
市
V悶hw
-u
421 EXTRACORPOREAL CIRCULATION
Table 11 Brain
(Degeneration of ganglion
cells) (Niss!’s stainJ
(羽」ヨ
o戸一)、円ωιo“ロ伺
CH
一525
一)己内w己
c
E亡cωい肩叫=
ω」U』釦一)一土一一
ECF一,J
己=EE〈一一土一
xb亡cu一己よと
ωυ
一一一一
CEZUEこじ巳リAM
--456
~1 0. ' ;! :七百' 7一一一 48 ~
'"' I 9一一一 48 : -~ ' .r,
IO一一一 25 ' -0 l記
13一一一 26 .司
11一一一 48 勺
12 +土+ 48 己14一一一 48 c 15一一一 48 ! :;;
16一一土 2 17一一土 3 I司
υ18一一- 5 I ll 門 19一一土 5 ℃
号I20一一+ 7 i 。l』 F円。21一一- 48 ~
22一一土 48 ~
I 23 -土- 2 i 24一一一 3 25一一一 5 26一一一 0 31一一+ 5 32一一一 2
同 I35土土土 12己 I43一一土 3 c ・-
占 I30土+ + 48 33一一+ 48 36ー士土 4837土士+ 48 39 + + + 192 42 * * * 96 44 +十件 48
Lung Table 10
且ヨ
EO
ιヨ三円)
℃
ω勾})
日】沼む勺司ω〉圏、,』ロ泊
一一一
件一一
一一一
件一一
一一+
+++
+一土
+一+
件+柵
++掛
一456
〈][
ι=20
I IOー士一 一一一+一一一 25
自i13土特一一一一一一一一 26
巳‘
g i 11一一一 一一一一+一一 48 I 1'(
占i12ー+土一一一+ + + -48 ' -~ - I 14ー+一一一一一+ー+ 48 ' ~
I 15ー+一一一一一一一一 48 ~
16 +一一一一一一一++ 2 17 +件一一一一一一一一 3 I司
~118 ー士一一一一一一+- 5 : ~ v I 19 +一一一一一一一一一 5 I℃
昔I20 + +一一一一+一+ー 7 。|一一一一一一一一一 ← 』 ||唱。i21 +一一 一一一一一一一 48 I ~ I 22一一一一一一一一一一 48 : ~
"' 23ー + 一一一一十一一+ 2 I 24ー+一一一一+一+- 3 I
25 + * + + + + + 一 一 + 5 I 26 + *一+ー+一+-- 0 ,-g 31ー+一一一一+一一十 5 • -is 32 + + +一 一++ー一+ 2 I
同 I35 + -tt +一一一士一一一 12 I 号I43ー++一一一+一一+ 3 I
0 I 一一一←一一← • 占I30ー++一一一++一件 48
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
日》πω
-v
48
48
7一一一一ー一一件一一
9一一++一一++一+
-umvbt
-vω〉目〉」ヨザ山
(己ロCZ)
hω且
OHSdωCH
一525
匂口ω己
2ωコ℃邑
EC』』戸七回口ω一ωE口、一
11
盟
tECEロωロ仏
的
zss-ぉ〈
E阿部h』品目同
一一旬、主詰一E〉一伺』CUEE4uロ-H
「ghuDH円七、内』凶
同一。ω〉一CE同-
戸
ω岩田》円高一凶
「む一FhυC』【{一?CMH
ωω一口同』UEO』《HE--戸
ω制何回》コ
xω
ccznu出口
3υ
む出
2」』
CEωE
CEHRwg己ω品×凶
七む〉
TP』ロ山
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.