382 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



shivering, general anesthesia induced with morphine sulphate { 10 mg./kg.) and 

 pentobarbital (15 mg./kg.) intravenously was employed. It was realized that this 

 might increase the stress of the procedure, but the factor was kept constant by its 

 application to all animals, including the control dogs. The tracheas were intubated 

 perorally, but insufflation was not employed. The anesthetized animals were wrapped 

 in rubberized blankets through which refrigerated fluid was circulated until their 

 temperature reached 31° C. Parallel controls were treated identically except for 

 the cooling. Chlorpromazine was given in dosages of 50 and 100 mg. intramuscu- 

 larly one to two hours before bleeding to one group and in 5 mg. doses to another. 

 The difference in 50 mg. and 100 mg. dosage has no statistical significance, both 

 being large doses for the dog. Parallel controls were treated identically except they 

 were not given the drug. In the series receiving coml)ined therapy, chlorpromazine 

 was administered in dosage of 50 mg. approximately one hour before initiation of 

 cooling, and on the average approximately two hours before the beginning of the 

 bleeding to one group, and in 5 mg. doses to another. 



The experiment was performed on 46 dogs with hypothermia alone. 45 dogs 

 with 50 mg. of chlorpromazine, 20 dogs with 5 mg. of chlorpromazine, 3S dogs 

 with combined chlorpromazine (50 mg.) and hypothermia, 14 dogs with combined 

 chlorpromazine (5 mg. ) and hypothermia, and 50 control dogs. Slight (1-2° C.) 

 cooling was secured by the autonomolytic drug alone, and cooling was achieved 

 somewhat faster in the dogs receiving the drug before the application of surface 

 cooling. The discrepancy in number of controls is due to the simultaneous use of 

 one control to parallel one or more of the other groups. 



Results. Originally the survival period was arbitrarily determined at the end of 

 24 hours, since the majority of deaths occurred well within this time. INIost of the 

 controls expired at or soon after the end-point. Subsequently it seemed desirable 

 to determine ultimate survival, based upon a minimum period of 2 weeks. Accord- 

 ingly the experiments were repeated on additional groups of animals for this pur- 

 pose. Certain studies carried out in the first groups were also repeated in the 

 second groups thus providing additional data. 



Both the immediate as well as the ultimate survival rates were increased in all 

 of the experiments as compared with the control animals (figs. 1 and 2). As might 

 be expected the ultimate survival rates were somewhat less, except for one group 

 of animals, than the immediate survival rates, since in the former groups a number 

 of variables are introduced, such as bacterial contamination and lack of supportive 

 measure. In this connection it has been observed in another experiment conducted 

 in our laboratory that the coml)ined use of anesthesia and hypothermia alone is 

 followed by a mortality of 10 per cent when anti-bacterial therapy is not employed.-" 

 The high proportion of rapid deaths in the control dogs, which is slightly greater 

 than that oljtained in our previous studies, testifies to the severity of the stress. 

 Although there was a significant increase in survival rate among the dogs that were 

 cooled before being bled, and an even greater increase in those receiving chlorproma- 

 zine in both large and small doses prior to the experiment, the dogs treated by the 

 combined use of hypothermia and chlorpromazine in large doses showed the most 

 pronounced increase in survival. The combined use of hypothermia and small doses 

 of chlorpromazine resulted in a survival rate greater than that following use of 

 the drug alone in comjiarable dosage, but slightly less than when used alone in 



