Perfusion Cooling by Pulsatile Flow Yoshitaka SASAKI ABSTRACT: Organ temperature changes and the temperature gradient between organs with cooling and rewarming were studied in rabbits using pulsatile flow perfusion. The temperature gradient between organs was within 3 ~ At the initial stage of cooling and rewarming, organ temperatures changed rapidly. During circulatory arrest, organ temperatures rose gradually. Brain temperature changes were similar to other organs. KEY WORDS: Cardiopulmonary bypass, surface cooling, pulsatile flow, temperature gradient between organs. INTRODUCTION
T h e r e are several methods of intraoperative support used in open heart surgery. These include cardiopulmonary bypass, surface cooling and perlusion cooling. Each has advantages and disadvantages. Perfusion cooling, as opposed to surface cooling, is cooling of the body by perfusion with a perfusate. The circulation can be stopped at the desired temperature and cardiac operation performed. The body is then rewarmed by perfusion. A roller pump, which provides continuous flow is usually used for this procedure. The greatest disadvantage of this technique, however, is that a considerable temperature difference occurs between the organs during cooling and rewarming.1,2,5,6,10,12,14,18,21 With continuous flow, the blood ejected by the pump does not reach the peripheral areas of the body evenly resulting in the partial cooling and rewarming, which in turn produces the undesirable temperature gradient between the organs. If, however, perfusion is done by pulsatile flow as in the physiological circulation, and ganglion blockades are used to inhibit vascular contraction at low temperatures, this temperature gradient between organs should be minimized. To determine if this is in fact the case, rabbits were cooled and rewarmed by perfusionusing a newly designed small pulsatile pump. The temperatures of several organs were measured, and temperature changes and the temperature gradient between organs studied. MATERIALS AND METHODS
Thirty-eight rabbits weighing 3.0 to 4.0 Kg. were used, but 18 were excluded because of the occurrence of cardiac arrest or bleeding before the perfusion started. Twenty rabbits were divided equally into two groups. Ten rabbits (group l) were cooled for 15 minutes and rewarmed for 45 minutes. Another 10 rabbits (group 2) were cooled for 15 minutes, the circulation was stopped for 15 minutes and then rewarmed for 45 minutes, ] mg.IKg, of triflupromazine (Fig. I). Thirty minutes to one hour before the perfusion 0.01 mg./Kg, of atropine sulfate and I mg.]Kg, of promcthazine hydroch]oride were injected intramuscularly as premedication. The rabbit was then fixed on the table in a supine position. A tracheotomy was performed under local anesthesia, and a Ayre's tube was inserted into the trachea. At this point, assisted or controlled ventilation was begun with
From the Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan JAPANESEJOURNAL OFSURGERYVOL. 7, No. 2, pp. 96-104, 1977
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Perfusion Cooling by Pulsatile Flow
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100 per cent oxygen. For general anesthesia, 0.25 mg./Kg, of droperidol and 1 mg./Kg. of pentazocine were infused intravenously beginning immediately after the tracheotomy. Gallamine or pancuronium bromide was administered intravenously as a muscle relaxant. Ten rag. of heparin was also administered intravenously as an anticoagulant. A specially designed pulsatile pump 19 was used in these experiments. It is driven by a coil spring. The beat rate, stroke volume and the highest blood pressure could be independently controlled. As the priming fluid for the bubble oxygenator, ca 360 ml. of rabbit blood, ca 200 ml. of lactated Ringer solution, 3 ml./Kg, of seven per cent sodium bicarbonate, 5 ml./Kg, of 20 per cent mannitol, 1 mg./Kg, ofdexamethazone, 0.25 mg./Kg. of droperidol, 1 mg./Kg, of pentazocine, 3 mg./Kg, of triflupromazine and 10rag. of heparin were used. A Brown-Harrison type heat exchanger was used for cooling and rewarming. For arterial return, a specially designed T-shaped cannula with an outer diameter of three mm. was inserted into the abdominal aorta. For venous return a straight vinyl tube was inserted into the right ventricle through the right atrium. During the perfusion pulmonary artery was cross-clamped. The perfusion conditions were 80--100 beats/min, of pulse, nearly 100 ml./Kg./min, of output and nearly 100 mmHg. of arterial systolic pressure. The temperatures of perfusate, esophagus, rectum, brain, heart and liver were measured every five minutes with an electric thermometer. RESULTS
The temperature changes of the perfusate and organs during cooling followed by immediate rewarming (group 1) are shown graphically in Fig. 2 and during cooling,
38 RABBITS
I
PERFUSED (20 RABBITS)
DIED (18 RABBITS)
I
GROUP 2 (10 RABBITS)
GROUP 1 (10 RABBITS)
f 45 MIN. REWARMING
9 9
..1 9 9
Fig. 1. Materials and cooling methods.
Sasaki
98
Jap. J. Surg. June 1977
t
30
_
'
.... ~
~l
; -//'D/
~!t
' "/
I/] 20
'
X x
[I [/
" ~
10
o
Fig. 2.
.....
COOLING
o
o ESOPHAGUS
:x. . . . . .
• RECTUM
-*
-" LIVER
REWARMING
15
~o
15
do MIN
Temperature change during cooling followed by immediate rewarming (group 1).
circulatory arrest and rewarming (group 2) in Fig. 3. Each point represents the mean value of the 10 rabbits. The temperature gradient between the perfusate and organs is shown graphically in Fig. 4 for group 1 and Fig. 5 for group 2. The temperature gradient between the two organs of highest and lowest temperature was calculated in each rabbit at different time intervals. The greatest value at each time is the m a x i m u m value. The smallest value is the minimum value. T h e mean value was then calculated. The results are shown in Table 1 and Fig. 6 for group 1 and Table 2 and Fig. 7 for group 2.
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Perfusion Cooling by Pulsatile Flow
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~
40-
x~
//
30
20-
10
. . . - - - -.-=-~-_.--- ~
COOLING
o
o ESOPHAGUS
x. . . .
x RECTUM
......
BRAIN
n. . . . . . . .
m
HEART
A
9 LIVER
REWARMING CIRCULATORY ARREST
0 Fig. 3.
15
30
4~5
1
60
7~5MIN.
Temperature change during cooling, circulatory arrest and rewarming (group 2).
DiscussioN
D u r i n g cooling, o r g a n t e m p e r a t u r e s fell w i t h i n a narrow, s m o o t h l y c u r v e d t e m p e r a ture b a n d as seen in Figs. 2 a n d 3. W i t h cooling for 15 m i n u t e s o r g a n t e m p e r a t u r e s fell to a b o u t 18~ w i t h no g r e a t t e m p e r a t u r e g r a d i e n t b e t w e e n the organs. T h e h e a r t t e m p e r a ture before cooling was s o m e w h a t lower t h a n o t h e r organs. T h e h e a r t m a y have been cooled b y the r o o m t e m p e r a t u r e w h e n the chest was opened. W h e n the r a b b i t s were r e w a r m e d i m m e d i a t e l y after cooling (group 1), the o r g a n t e m p e r a t u r e rose in a n a r r o w , s m o o t h l y c u r v e d t e m p e r a t u r e b a n d as shown in Fig. 2. T h e h e a r t t e m p e r a t u r e was slightly lower t h a n o t h e r organs, p r o b a b l y d u e to t h o r a c o t o m y . D u r i n g c i r c u l a t o r y arrest in g r o u p 2, o r g a n t e m p e r a t u r e s rose g r a d u a l l y as shown in Fig. 3 a n d is quite different from surface cooling in w h i c h o r g a n t e m p e r a t u r e s usually fall g r a d u a l l y 3 a , is D u r i n g r e w a r m i n g after c i r c u l a t o r y arrest, o r g a n t e m p e r a t u r e changes were similar to those w i t h o u t i n t e r v e n i n g c i r c u l a t o r y arrest (group 1). O r g a n t e m p e r a t u r e s
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Jap. J. Surg. June 1977
~ o
o ESOPHAGUS
x .....
•
......
RECTUM BRAIN
[]. . . . . . . . . . . o H E A R T A
a
LIVER
10
COOLING
REWARMING
-10
0
1'5
30
4'5
dO MIN
Fig. 4. The temperature gradient between the perfusate and the organs (group 1). rose within a narrow temperature band as shown in Fig. 3. The heart temperature was somewhat lower than other organs as in group 1. One of the most serious problems with perfusion cooling is the possible brain damage. 1,3,4,7,9,12,13,16,17,20 In the present series of experiments, the brain was cooled and rewarmed along with other organs. All organs, including brain could be cooled and rewarmed quite evenly by pulsatile perfusion. In both groups, the temperature gradient between the perfusate and the organs was greatest at the initial stage of cooling and rewarming but this gradient decreased as perfusion progressed. In other words, the organ temperature gradually approached perfusate temperature as perfusion continued indicating that cooling and rewarming by perfusion was accomplished smoothly. Organ temperatures would not approximate the perfusate temperature if the perfusion did not proceed smoothly.
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101
~
o
o ESOPHAGUS
x. . . .
• RECTUM
......
BRAIN
......... ~ HEART *
,0 Ik
~ LIVER
0
COOLING
REWARMING
-10-
CI RCULATORY ARREST T
15 Fig. 5.
30
15
6'0
75 MIN.
T h e temperature gradient between the perfusate and the organs (group 2). T a b l e . 1.
T h e temperature gradient between organs during 15 minutes cooling followed by immediate rewarming (group 1)
Cooling
Rewarming T i m e (min.)
Temperature gradient~ Max. Mean Min. T a b l e 2.
0
5
10.6 6.3 4.4 2.6 0.8 0.7
10
15
20
25
30
35
40
45
50
55
60
3.3 2.2 0.8
2.1 1.2 0.7
3.2 2.1 0.7
4.7 2.0 0.8
5.7 2.1 0.2
5.8 2.1 0.9
5.6 1.8 0.4
5.0 1.7 0.7
4.8 1.7 0.7
4.9 1.6 0.8
4.5 1.6 0.4
T h e temperature gradient between organs during 15 minutes cooling, 15 minutes circulatory arrest followed by rewarming (group 2) Cooling
10
15
20
25
Rewarming
Temperature gradient ~
0
Max.
9.2 6.7 3.7 3.8 3.3 3.7 4.3 2.6 2.9 3.4 2.7 3.2 2.5 2.8 2.5 2.6 3.1 3.1 2.5 1.9 1.9 2.1 2.0 1.7 1.9 2.1 1.6 1.9 1.6 1.6 1.4 1.5 1.1 1.5 0.9 0.7 0.6 0.7 1.0 0.8 0.8 0.8 0.7 1.2 0.6 0.7 0.3 0.6
Mean Miu.
5
Circulatory arrest T i m e (rain.) 30
35
40
45
50
55
60
65
70
75
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Jap. J. Surg. June 1977
*C 16
REWARMING
COOLING 10
I MAX. MEAN MIN.
T I
III
t
I
15
30
6~0 MIN.
45
Fig. 6. The temperature gradient between organs (group 1).
*C 16 t
MAX. MEAN MIN.
10 COOLING
CIRCULATORY REWARMING ARREST
_It
tt 15
30
15
60
75 MIN.
Fig. 7. The temperature gradient between organs (group 2). T h e m a x i m u m temperature gradient between organs before the perfusion was 10.6 ~ in group 1, and 9.2 ~ in group 2. The m a x i m u m temperature gradient during perfusion obtained five minutes after the beginning of perfusion was 6.3~ in group 1, and 6.7~ in group 2, which are much smaller than in the previous study with a roller pump, 18 i.e. 16.5~ T h e mean value of the m a x i m u m temperature gradient except before cooling were observed five minutes after the beginning of perfusion in both groups, i.e. 2.6~ in group 1 and 3.1~ in group 2, which are also smaller than the 10~ gradient in our studies with a roller pump. 18 Because the purpose of perfusion cooling is to stop the circulation during the operation, the organ temperature and the temperature gradient between organs at the termination of cooling are most important. In the present study, the mean temperature gradient in
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group 1 was 1.2 ~ a n d 1.9 ~ in group 2 using a pulsatile p u m p which are considerably smaller t h a n in our previous studies using a roller pump.18 W i t h the roller p u m p , the temperature g r a d i e n t was 3.8~ w h e n the rabbits were cooled slowly for 60 minutes, 4 . 5 ~ when cooled r a p i d l y for 60 minutes, 8.0 ~ for 20 minutes, 10.1 ~ for 15 m i n u t e s a n d 9.4 ~ for 10 minutes. T h u s the present investigation clearly indicated that the t e m p e r a t u r e gradient between organs d u r i n g cooling a n d r e w a r m i n g can be m i n i m i z e d by perfusion cooling a n d r e w a r m i n g by pulsatile flow with ganglion blockades. ACKNOWLEDGEMENT T h e substance of this work was reported at the 10th I n t e r n a t i o n a l Congress of Angiology o n S e p t e m b e r 2nd, 1976 in Tokyo, J a p a n . T h e a u t h o r wishes to t h a n k the Director, Professor I s a m u Hashimoto, a n d the m e m b e r s of the D e p a r t m e n t of Surgery, K y o t o Prefectural U n i v e r s i t y of M e d i c i n e for their general support, criticism a n d cooperation d u r i n g the investigation. (Received for publication on December 20, 1976) References 1. Almond, C.H., Jones, J.C., Synder, H.M., Grant, S.M. and Meyer, B.W.: Cooling gradient and brain damage with deep hypothermia, J. Thorac. Cardiovasc. Surg. 48: 890-897, 1964. 2. Belsey, R.H.R., Dowlatshahi, K., Keen, G. and Skinner, D.B. : Profound hypothermia in cardiac surgery, J. Thorac. Cardiovasc. Surg. 56: 497-509, 1968. 3. Bj6rk, V.O. and Huhquist, G.: Contraindication to profound hypothermia in openheart surgery, J. Thorac. Cardiovasc. Surg. 44: 1-13, 1962. 4. Bj6rk, V.O. and Hultquist, G. : Brain damage in children after deep hypothermia for openheart surgery, Thorax 15: 284-291, 1960. 5. Bj6rk, V.O. and Holmdahl, M.H.: The oxygen consumption in man under deep hypothermia and the safe period of circulatory arrest, J. Thorac. Cardiovasc. Surg. 42: 392401, 1961. 6. Brian, G., Barratt-Boyes, B.C., Simpson, M. and Neutze, J.M.: Intracardiac surgery in neonates and infants using deep hypothermia with surface cooling and limited cardiopulmonary bypass, Circulation 18 & 19 (Suppl.) 1 : 25-30, 1971. 7. Brunberg, J.A., Reilly, E.L. and Doty, D.B.: Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest, Circulation 49 & 50 (Suppl.) 2: 60-68, 1974. 8. Castaneda A.R., Lawberti, J., Sade, R.M., Williams, R.G. and Nadas, A.S.: Openheart surgery during the first three months of life, J. Thorac. Cardiovasc. Surg. 68: 719731, 1974.
9. Egerton, N., Egerton, W.S. and Kay, J.H.: Neurologic changes following profound hypothermia, Ann. Surg. 157 : 366-374, 1963. 10. Gordon, A.S., Meyer, B.W. and Jones, J.C.: Open-heart surgery using deep hypothermia without an oxygenator, J. Thorac.Cardiovasc. Surg. 40: 787-812, 1960. 11. Harris, E.A.: Metabolic aspect of profound hypothermia, Heart Diseases in Infancy: 65-74, Churchill Livingstone, Edinburgh and London, 1973. 12. Horiuchi, T., Tanaka, S. and Sato, K.: Hypothermia, Kyobu Geka (Jpn. j . Thorac. Surg.) 27: 1035-1037, 1974 (in Japanese). 13. Matsumoto, A., Ide, K., Sato, J., Kondo, J., Goto, H., Kouguchi, N., Kawahara, S., Nishi, H., Yazawa, J., Tomita, Y. and Wada, T. : Open heart surgery under the profound hypothermia by using the surface cooling combined with extracorporeal circulation, Kyobu Geka (Jpn. J. Thorac. Surg.) 24: 229235, 1971 (in Japanese). 14. Peirce II, E.C., Wallis, D.E., Law, N.P. and Conard, J. : Studies in perfusion hypothermia with special reference to "deep hypothermia" and circulatory arrest, J. Surg. Res. 5: 296-305, 1965. 15. Rittenhouse, E.A., Ito, C.S. Mohri, H. and Merendino, K.A. : Circulatory dynamics during surface-induced deep hypothermia and after cardiac arrest for one hour, J. Thorac. Cardiovasc. Surg. 61 : 359-369, 1971. 16. Rittenhouse, E.A., Mohri, H., Dillard, D.H. and Merendino, K.A. : Deep hypothermia in cardiovascular surgery, Ann. Thorac. Surg. 17: 63-98, 1974.
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17. Sabramanian, S. and Wagner, H.: Correction of transposition of the great arteries in infants under surface-induced deep hypothermia, Ann. Thorac. Surg. 16: 391~,01, 1973. 18. Sasaki, Y., Uga, S., Sakabe, H., Ohga, K., Tanabe, S., Nakamura, A., Shirakata, S., Nakamoto, T., Hara, T. and Hashimoto, I.: Organ temperature gradients by perfusion cooling using ganglion blockades, Kyoto Furitsu Ikadaigaku Zasshi (J. Kyoto Pref. Univ. Med.) 84: 77t-782, 1975 (in Japanese).
Jap. J. Surg. June 1977 19. Sasaki, Y., Uga, S., Sakabe, H., Ohga, K., Tanabe, S., Nakamura, A., Shirakata, S., Nakamoto, T., Hara, T. and Hashimoto, I.: A small pulsatile pump, Jinko Zoki (Artificial Organs) 4 (Suppl.): 23, 1975 (in Japanese). 20. Silberstone, J.T., Taunahill, M.H. and Ireland, J.A.: Psychiatric aspect of profound hypothermia in open-heart surgery, J. Thorac. Cardiovasc. Surg. 59: 193-200, 1970. 2I. Wolfson, S.K., Yalav, E. and Eisenstat, S.: An isothermic technique for profound hypothermia and its effect on metabolic acidosis, J. Thorac. Cardiovasc.Surg. 45: 466-475, 1963.
T h e r e are several methods of intraoperative support used in open heart surgery. These include cardiopulmonary bypass, surface cooling and perlusion cooling. Each has advantages and disadvantages. Perfusion cooling, as opposed to surface cooling, is cooling of the body by perfusion with a perfusate. The circulation can be stopped at the desired temperature and cardiac operation performed. The body is then rewarmed by perfusion. A roller pump, which provides continuous flow is usually used for this procedure. The greatest disadvantage of this technique, however, is that a considerable temperature difference occurs between the organs during cooling and rewarming.1,2,5,6,10,12,14,18,21 With continuous flow, the blood ejected by the pump does not reach the peripheral areas of the body evenly resulting in the partial cooling and rewarming, which in turn produces the undesirable temperature gradient between the organs. If, however, perfusion is done by pulsatile flow as in the physiological circulation, and ganglion blockades are used to inhibit vascular contraction at low temperatures, this temperature gradient between organs should be minimized. To determine if this is in fact the case, rabbits were cooled and rewarmed by perfusionusing a newly designed small pulsatile pump. The temperatures of several organs were measured, and temperature changes and the temperature gradient between organs studied. MATERIALS AND METHODS
Thirty-eight rabbits weighing 3.0 to 4.0 Kg. were used, but 18 were excluded because of the occurrence of cardiac arrest or bleeding before the perfusion started. Twenty rabbits were divided equally into two groups. Ten rabbits (group l) were cooled for 15 minutes and rewarmed for 45 minutes. Another 10 rabbits (group 2) were cooled for 15 minutes, the circulation was stopped for 15 minutes and then rewarmed for 45 minutes, ] mg.IKg, of triflupromazine (Fig. I). Thirty minutes to one hour before the perfusion 0.01 mg./Kg, of atropine sulfate and I mg.]Kg, of promcthazine hydroch]oride were injected intramuscularly as premedication. The rabbit was then fixed on the table in a supine position. A tracheotomy was performed under local anesthesia, and a Ayre's tube was inserted into the trachea. At this point, assisted or controlled ventilation was begun with
From the Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan JAPANESEJOURNAL OFSURGERYVOL. 7, No. 2, pp. 96-104, 1977
Volume 7 Number 2
Perfusion Cooling by Pulsatile Flow
97
100 per cent oxygen. For general anesthesia, 0.25 mg./Kg, of droperidol and 1 mg./Kg. of pentazocine were infused intravenously beginning immediately after the tracheotomy. Gallamine or pancuronium bromide was administered intravenously as a muscle relaxant. Ten rag. of heparin was also administered intravenously as an anticoagulant. A specially designed pulsatile pump 19 was used in these experiments. It is driven by a coil spring. The beat rate, stroke volume and the highest blood pressure could be independently controlled. As the priming fluid for the bubble oxygenator, ca 360 ml. of rabbit blood, ca 200 ml. of lactated Ringer solution, 3 ml./Kg, of seven per cent sodium bicarbonate, 5 ml./Kg, of 20 per cent mannitol, 1 mg./Kg, ofdexamethazone, 0.25 mg./Kg. of droperidol, 1 mg./Kg, of pentazocine, 3 mg./Kg, of triflupromazine and 10rag. of heparin were used. A Brown-Harrison type heat exchanger was used for cooling and rewarming. For arterial return, a specially designed T-shaped cannula with an outer diameter of three mm. was inserted into the abdominal aorta. For venous return a straight vinyl tube was inserted into the right ventricle through the right atrium. During the perfusion pulmonary artery was cross-clamped. The perfusion conditions were 80--100 beats/min, of pulse, nearly 100 ml./Kg./min, of output and nearly 100 mmHg. of arterial systolic pressure. The temperatures of perfusate, esophagus, rectum, brain, heart and liver were measured every five minutes with an electric thermometer. RESULTS
The temperature changes of the perfusate and organs during cooling followed by immediate rewarming (group 1) are shown graphically in Fig. 2 and during cooling,
38 RABBITS
I
PERFUSED (20 RABBITS)
DIED (18 RABBITS)
I
GROUP 2 (10 RABBITS)
GROUP 1 (10 RABBITS)
f 45 MIN. REWARMING
9 9
..1 9 9
Fig. 1. Materials and cooling methods.
Sasaki
98
Jap. J. Surg. June 1977
t
30
_
'
.... ~
~l
; -//'D/
~!t
' "/
I/] 20
'
X x
[I [/
" ~
10
o
Fig. 2.
.....
COOLING
o
o ESOPHAGUS
:x. . . . . .
• RECTUM
-*
-" LIVER
REWARMING
15
~o
15
do MIN
Temperature change during cooling followed by immediate rewarming (group 1).
circulatory arrest and rewarming (group 2) in Fig. 3. Each point represents the mean value of the 10 rabbits. The temperature gradient between the perfusate and organs is shown graphically in Fig. 4 for group 1 and Fig. 5 for group 2. The temperature gradient between the two organs of highest and lowest temperature was calculated in each rabbit at different time intervals. The greatest value at each time is the m a x i m u m value. The smallest value is the minimum value. T h e mean value was then calculated. The results are shown in Table 1 and Fig. 6 for group 1 and Table 2 and Fig. 7 for group 2.
Volume 7
Number 2
Perfusion Cooling by Pulsatile Flow
99
~
40-
x~
//
30
20-
10
. . . - - - -.-=-~-_.--- ~
COOLING
o
o ESOPHAGUS
x. . . .
x RECTUM
......
BRAIN
n. . . . . . . .
m
HEART
A
9 LIVER
REWARMING CIRCULATORY ARREST
0 Fig. 3.
15
30
4~5
1
60
7~5MIN.
Temperature change during cooling, circulatory arrest and rewarming (group 2).
DiscussioN
D u r i n g cooling, o r g a n t e m p e r a t u r e s fell w i t h i n a narrow, s m o o t h l y c u r v e d t e m p e r a ture b a n d as seen in Figs. 2 a n d 3. W i t h cooling for 15 m i n u t e s o r g a n t e m p e r a t u r e s fell to a b o u t 18~ w i t h no g r e a t t e m p e r a t u r e g r a d i e n t b e t w e e n the organs. T h e h e a r t t e m p e r a ture before cooling was s o m e w h a t lower t h a n o t h e r organs. T h e h e a r t m a y have been cooled b y the r o o m t e m p e r a t u r e w h e n the chest was opened. W h e n the r a b b i t s were r e w a r m e d i m m e d i a t e l y after cooling (group 1), the o r g a n t e m p e r a t u r e rose in a n a r r o w , s m o o t h l y c u r v e d t e m p e r a t u r e b a n d as shown in Fig. 2. T h e h e a r t t e m p e r a t u r e was slightly lower t h a n o t h e r organs, p r o b a b l y d u e to t h o r a c o t o m y . D u r i n g c i r c u l a t o r y arrest in g r o u p 2, o r g a n t e m p e r a t u r e s rose g r a d u a l l y as shown in Fig. 3 a n d is quite different from surface cooling in w h i c h o r g a n t e m p e r a t u r e s usually fall g r a d u a l l y 3 a , is D u r i n g r e w a r m i n g after c i r c u l a t o r y arrest, o r g a n t e m p e r a t u r e changes were similar to those w i t h o u t i n t e r v e n i n g c i r c u l a t o r y arrest (group 1). O r g a n t e m p e r a t u r e s
Sasaki
100
Jap. J. Surg. June 1977
~ o
o ESOPHAGUS
x .....
•
......
RECTUM BRAIN
[]. . . . . . . . . . . o H E A R T A
a
LIVER
10
COOLING
REWARMING
-10
0
1'5
30
4'5
dO MIN
Fig. 4. The temperature gradient between the perfusate and the organs (group 1). rose within a narrow temperature band as shown in Fig. 3. The heart temperature was somewhat lower than other organs as in group 1. One of the most serious problems with perfusion cooling is the possible brain damage. 1,3,4,7,9,12,13,16,17,20 In the present series of experiments, the brain was cooled and rewarmed along with other organs. All organs, including brain could be cooled and rewarmed quite evenly by pulsatile perfusion. In both groups, the temperature gradient between the perfusate and the organs was greatest at the initial stage of cooling and rewarming but this gradient decreased as perfusion progressed. In other words, the organ temperature gradually approached perfusate temperature as perfusion continued indicating that cooling and rewarming by perfusion was accomplished smoothly. Organ temperatures would not approximate the perfusate temperature if the perfusion did not proceed smoothly.
Volume 7 Number 2
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201
101
~
o
o ESOPHAGUS
x. . . .
• RECTUM
......
BRAIN
......... ~ HEART *
,0 Ik
~ LIVER
0
COOLING
REWARMING
-10-
CI RCULATORY ARREST T
15 Fig. 5.
30
15
6'0
75 MIN.
T h e temperature gradient between the perfusate and the organs (group 2). T a b l e . 1.
T h e temperature gradient between organs during 15 minutes cooling followed by immediate rewarming (group 1)
Cooling
Rewarming T i m e (min.)
Temperature gradient~ Max. Mean Min. T a b l e 2.
0
5
10.6 6.3 4.4 2.6 0.8 0.7
10
15
20
25
30
35
40
45
50
55
60
3.3 2.2 0.8
2.1 1.2 0.7
3.2 2.1 0.7
4.7 2.0 0.8
5.7 2.1 0.2
5.8 2.1 0.9
5.6 1.8 0.4
5.0 1.7 0.7
4.8 1.7 0.7
4.9 1.6 0.8
4.5 1.6 0.4
T h e temperature gradient between organs during 15 minutes cooling, 15 minutes circulatory arrest followed by rewarming (group 2) Cooling
10
15
20
25
Rewarming
Temperature gradient ~
0
Max.
9.2 6.7 3.7 3.8 3.3 3.7 4.3 2.6 2.9 3.4 2.7 3.2 2.5 2.8 2.5 2.6 3.1 3.1 2.5 1.9 1.9 2.1 2.0 1.7 1.9 2.1 1.6 1.9 1.6 1.6 1.4 1.5 1.1 1.5 0.9 0.7 0.6 0.7 1.0 0.8 0.8 0.8 0.7 1.2 0.6 0.7 0.3 0.6
Mean Miu.
5
Circulatory arrest T i m e (rain.) 30
35
40
45
50
55
60
65
70
75
Sasaki
102
Jap. J. Surg. June 1977
*C 16
REWARMING
COOLING 10
I MAX. MEAN MIN.
T I
III
t
I
15
30
6~0 MIN.
45
Fig. 6. The temperature gradient between organs (group 1).
*C 16 t
MAX. MEAN MIN.
10 COOLING
CIRCULATORY REWARMING ARREST
_It
tt 15
30
15
60
75 MIN.
Fig. 7. The temperature gradient between organs (group 2). T h e m a x i m u m temperature gradient between organs before the perfusion was 10.6 ~ in group 1, and 9.2 ~ in group 2. The m a x i m u m temperature gradient during perfusion obtained five minutes after the beginning of perfusion was 6.3~ in group 1, and 6.7~ in group 2, which are much smaller than in the previous study with a roller pump, 18 i.e. 16.5~ T h e mean value of the m a x i m u m temperature gradient except before cooling were observed five minutes after the beginning of perfusion in both groups, i.e. 2.6~ in group 1 and 3.1~ in group 2, which are also smaller than the 10~ gradient in our studies with a roller pump. 18 Because the purpose of perfusion cooling is to stop the circulation during the operation, the organ temperature and the temperature gradient between organs at the termination of cooling are most important. In the present study, the mean temperature gradient in
Volume 7 Number 2
Perfusion Cooling by Pulsatile Flow
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group 1 was 1.2 ~ a n d 1.9 ~ in group 2 using a pulsatile p u m p which are considerably smaller t h a n in our previous studies using a roller pump.18 W i t h the roller p u m p , the temperature g r a d i e n t was 3.8~ w h e n the rabbits were cooled slowly for 60 minutes, 4 . 5 ~ when cooled r a p i d l y for 60 minutes, 8.0 ~ for 20 minutes, 10.1 ~ for 15 m i n u t e s a n d 9.4 ~ for 10 minutes. T h u s the present investigation clearly indicated that the t e m p e r a t u r e gradient between organs d u r i n g cooling a n d r e w a r m i n g can be m i n i m i z e d by perfusion cooling a n d r e w a r m i n g by pulsatile flow with ganglion blockades. ACKNOWLEDGEMENT T h e substance of this work was reported at the 10th I n t e r n a t i o n a l Congress of Angiology o n S e p t e m b e r 2nd, 1976 in Tokyo, J a p a n . T h e a u t h o r wishes to t h a n k the Director, Professor I s a m u Hashimoto, a n d the m e m b e r s of the D e p a r t m e n t of Surgery, K y o t o Prefectural U n i v e r s i t y of M e d i c i n e for their general support, criticism a n d cooperation d u r i n g the investigation. (Received for publication on December 20, 1976) References 1. Almond, C.H., Jones, J.C., Synder, H.M., Grant, S.M. and Meyer, B.W.: Cooling gradient and brain damage with deep hypothermia, J. Thorac. Cardiovasc. Surg. 48: 890-897, 1964. 2. Belsey, R.H.R., Dowlatshahi, K., Keen, G. and Skinner, D.B. : Profound hypothermia in cardiac surgery, J. Thorac. Cardiovasc. Surg. 56: 497-509, 1968. 3. Bj6rk, V.O. and Huhquist, G.: Contraindication to profound hypothermia in openheart surgery, J. Thorac. Cardiovasc. Surg. 44: 1-13, 1962. 4. Bj6rk, V.O. and Hultquist, G. : Brain damage in children after deep hypothermia for openheart surgery, Thorax 15: 284-291, 1960. 5. Bj6rk, V.O. and Holmdahl, M.H.: The oxygen consumption in man under deep hypothermia and the safe period of circulatory arrest, J. Thorac. Cardiovasc. Surg. 42: 392401, 1961. 6. Brian, G., Barratt-Boyes, B.C., Simpson, M. and Neutze, J.M.: Intracardiac surgery in neonates and infants using deep hypothermia with surface cooling and limited cardiopulmonary bypass, Circulation 18 & 19 (Suppl.) 1 : 25-30, 1971. 7. Brunberg, J.A., Reilly, E.L. and Doty, D.B.: Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest, Circulation 49 & 50 (Suppl.) 2: 60-68, 1974. 8. Castaneda A.R., Lawberti, J., Sade, R.M., Williams, R.G. and Nadas, A.S.: Openheart surgery during the first three months of life, J. Thorac. Cardiovasc. Surg. 68: 719731, 1974.
9. Egerton, N., Egerton, W.S. and Kay, J.H.: Neurologic changes following profound hypothermia, Ann. Surg. 157 : 366-374, 1963. 10. Gordon, A.S., Meyer, B.W. and Jones, J.C.: Open-heart surgery using deep hypothermia without an oxygenator, J. Thorac.Cardiovasc. Surg. 40: 787-812, 1960. 11. Harris, E.A.: Metabolic aspect of profound hypothermia, Heart Diseases in Infancy: 65-74, Churchill Livingstone, Edinburgh and London, 1973. 12. Horiuchi, T., Tanaka, S. and Sato, K.: Hypothermia, Kyobu Geka (Jpn. j . Thorac. Surg.) 27: 1035-1037, 1974 (in Japanese). 13. Matsumoto, A., Ide, K., Sato, J., Kondo, J., Goto, H., Kouguchi, N., Kawahara, S., Nishi, H., Yazawa, J., Tomita, Y. and Wada, T. : Open heart surgery under the profound hypothermia by using the surface cooling combined with extracorporeal circulation, Kyobu Geka (Jpn. J. Thorac. Surg.) 24: 229235, 1971 (in Japanese). 14. Peirce II, E.C., Wallis, D.E., Law, N.P. and Conard, J. : Studies in perfusion hypothermia with special reference to "deep hypothermia" and circulatory arrest, J. Surg. Res. 5: 296-305, 1965. 15. Rittenhouse, E.A., Ito, C.S. Mohri, H. and Merendino, K.A. : Circulatory dynamics during surface-induced deep hypothermia and after cardiac arrest for one hour, J. Thorac. Cardiovasc. Surg. 61 : 359-369, 1971. 16. Rittenhouse, E.A., Mohri, H., Dillard, D.H. and Merendino, K.A. : Deep hypothermia in cardiovascular surgery, Ann. Thorac. Surg. 17: 63-98, 1974.
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17. Sabramanian, S. and Wagner, H.: Correction of transposition of the great arteries in infants under surface-induced deep hypothermia, Ann. Thorac. Surg. 16: 391~,01, 1973. 18. Sasaki, Y., Uga, S., Sakabe, H., Ohga, K., Tanabe, S., Nakamura, A., Shirakata, S., Nakamoto, T., Hara, T. and Hashimoto, I.: Organ temperature gradients by perfusion cooling using ganglion blockades, Kyoto Furitsu Ikadaigaku Zasshi (J. Kyoto Pref. Univ. Med.) 84: 77t-782, 1975 (in Japanese).
Jap. J. Surg. June 1977 19. Sasaki, Y., Uga, S., Sakabe, H., Ohga, K., Tanabe, S., Nakamura, A., Shirakata, S., Nakamoto, T., Hara, T. and Hashimoto, I.: A small pulsatile pump, Jinko Zoki (Artificial Organs) 4 (Suppl.): 23, 1975 (in Japanese). 20. Silberstone, J.T., Taunahill, M.H. and Ireland, J.A.: Psychiatric aspect of profound hypothermia in open-heart surgery, J. Thorac. Cardiovasc. Surg. 59: 193-200, 1970. 2I. Wolfson, S.K., Yalav, E. and Eisenstat, S.: An isothermic technique for profound hypothermia and its effect on metabolic acidosis, J. Thorac. Cardiovasc.Surg. 45: 466-475, 1963.
