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 tempera- tures 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 There are several methods of intraoperative support used in open heart surgery. These include cardiopulmonary bypass, surface cooling and perlusion cooling. Each has advan- tages 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 perfusion using 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 be- cause 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 JAPANESE JOURNAL OF SURGERY VOL. 7, No. 2, pp. 96-104, 1977 Volume 7 Perfusion Cooling by Pulsatile Flow 97 Number 2 100 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 in- dependently 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 DIED (20 RABBITS) (18 RABBITS) I GROUP 2 (10 RABBITS) GROUP 1 (10 RABBITS) �9 �9 f 45 MIN. REWARMING ..1 �9 �9 Fig. 1. Materials and cooling methods. 98 Sasaki Jap. J. Surg. June 1977 t . . . . ~ . . . . . 30 _ ' ~l ; - / / 'D / ~!t ' "/ I / ] o o ESOPHAGUS 20 ' X x [ I [/ :x . . . . . . • RECTUM " ~ -* -" LIVER 10 COOLING REWARMING o 15 ~o 15 do MIN Fig. 2. 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 maximum value. The smallest value is the minimum value. The 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 Fig. 3. ~ 40- 30 20- 10 COOLING x~ . . . - - - -.-=-~-_.-- -~ / / o o ESOPHAGUS x . . . . x RECTUM . . . . . . BRAIN n . . . . . . . . m HEART A �9 LIVER REWARMING CIRCULATORY ARREST 1 0 15 30 4~5 60 7~5 MIN. Temperature change during cooling, circulatory arrest and rewarming (group 2). Discuss ioN During cooling, organ temperatures fell within a narrow, smoothly curved tempera- ture band as seen in Figs. 2 and 3. With cooling for 15 minutes organ temperatures fell to about 18~ with no great temperature gradient between the organs. The heart tempera- ture before cooling was somewhat lower than other organs. The heart may have been cooled by the room temperature when the chest was opened. When the rabbits were rewarmed immediate ly after cooling (group 1), the organ temperature rose in a narrow, smoothly curved temperature band as shown in Fig. 2. The heart temperature was slightly lower than other organs, probably due to thoracotomy. Dur ing circulatory arrest in group 2, organ temperatures rose gradual ly as shown in Fig. 3 and is quite different from surface cooling in which organ temperatures usually fall gradual ly3a, is Dur ing rewarming after circulatory arrest, organ temperature changes were similar to those without intervening circulatory arrest (group 1). Organ temperatures 100 Sasaki Jap. J. Surg. June 1977 Fig. 4. ~ 10 -10 o o ESOPHAGUS x . . . . . • RECTUM . . . . . . BRAIN [] . . . . . . . . . . . o HEART A a L IVER COOLING REWARMING 0 1'5 30 4'5 dO MIN 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 re- warmed 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 per- fusion 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 Perfusion Cooling by Pulsatile Flow 101 ~ 201 ,0 Ik o o ESOPHAGUS x . . . . • RECTUM . . . . . . BRAIN ......... ~ HEART * ~ LIVER 0 -10- COOLING REWARMING CI RCULATORY ARREST T 15 30 15 6'0 75 MIN. Fig. 5. The temperature gradient between the perfusate and the organs (group 2). Table. 1. The temperature gradient between organs during 15 minutes cooling followed by immediate rewarming (group 1) Cooling Rewarming Time (min.) Temperature 0 5 10 15 20 25 30 35 40 45 50 55 60 grad ient~ Max. 10.6 6.3 3.3 2.1 3.2 4.7 5.7 5.8 5.6 5.0 4.8 4.9 4.5 Mean 4.4 2.6 2.2 1.2 2.1 2.0 2.1 2.1 1.8 1.7 1.7 1.6 1.6 Min. 0.8 0.7 0.8 0.7 0.7 0.8 0.2 0.9 0.4 0.7 0.7 0.8 0.4 Table 2. The temperature gradient between organs during 15 minutes cooling, 15 minutes circulatory arrest followed by rewarming (group 2) Cooling Circulatory Rewarming arrest Time (rain.) 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 Temperature gradient ~ Max. Mean Miu. 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 0.6 102 Sasaki Jap. J. Surg. June 1977 *C 16 10 T I Fig. 6. COOLING t REWARMING I MAX. MEAN MIN. I 15 30 45 III 6~0 MIN. The temperature gradient between organs (group 1). *C 16 10 COOLING _It t MAX. MEAN MIN. CIRCULATORY ARREST tt REWARMING 15 30 15 60 75 MIN. Fig. 7. The temperature gradient between organs (group 2). The maximum temperature gradient between organs before the perfusion was 10.6 ~ in group 1, and 9.2 ~ in group 2. The maximum 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~ The mean value of the maximum 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 103 group 1 was 1.2 ~ and 1.9 ~ in group 2 using a pulsatile pump which are considerably smaller than in our previous studies using a roller pump.18 With the roller pump, the tem- perature gradient was 3.8~ when the rabbits were cooled slowly for 60 minutes, 4.5~ when cooled rapidly for 60 minutes, 8.0 ~ for 20 minutes, 10.1 ~ for 15 minutes and 9.4 ~ for 10 minutes. Thus the present investigation clearly indicated that the temperature gradient between organs during cooling and rewarming can be minimized by perfusion cooling and rewarming by pulsatile flow with ganglion blockades. ACKNOWLEDGEMENT The substance of this work was reported at the 10th International Congress of Angio- logy on September 2nd, 1976 in Tokyo, Japan. 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