388 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



The results obtained in animals receiving chlorpromazine were striking both in 

 terms of survival and increased tolerance to shock. This agent, however, produced 

 an alteration in the experiment which affects comparison of these animals with the 

 control and cooled animals. As previously indicated, the autonomolytic action of 

 the drug, when given in massive doses, reduced the vasoconstrictive response to 

 such an extent that bleeding was diminished in rate and volume. Survival and 

 tolerance figures then perhaps reflect only response to lesser stress, since it changes 

 the method to one of tolerance to hypotension rather than to blood lost. When the 

 dosage employed was small, however, a beneficial effect was secured with no altera- 

 tion in the amount of blood extracted, although it was done somewhat more slowly. 

 The possibility exists that chlorpromazine possesses a pharmacologic property 

 aside from its autonomolytic eft'ect to account for its beneficial action, but this latter 

 property seems to be the one of significance. Our results closely parallel those 

 demonstrated by Remington"- ^^' ^'^ and others using dibenamine, a drug with similar 

 but more pronounced autonomolytic properties. When the drug was administered 

 in doses that produced partial vasoplegia 1)ut still allowed some vasoconstrictive 

 response to bleeding, Remington was able to reduce significantly the mortality of 

 hemorrhagic and traumatic shock."'- "^ The noteworthy feature of these experiments 

 is the ability to extract from the treated animals the same volume of blood as from 

 the controls. The effects of the autonomolytic drug employed in this study, when 

 used in small doses, seem to add support to his findings. It had been previously 

 demonstrated that ether and spinal anesthesia, ergotamine and other autonomolytic 

 drugs, as well as surgical sympathectomy, permit great tolerance to the hypotension 

 that accompanies bleeding but reduce the tolerance to amount of blood lost.^^- **- "- 

 Fine-^ has apparently been unable to secure a protective action with dibenamine in 

 the method employed in this study, but perhaps the dosage employed was excessive, 

 as was the case in some of Wiggers' animals. '- 



The combined use of hypothermia and chlorpromazine. simulating in the ex- 

 perimental animal the therapeutic regimen of "artificial hibernation" used clinically, 

 produced striking results in regard to survival when compared with those secured 

 from their separate application. This study suggests that the benefits are derived 

 largely from the autonomolytic action of the drug employed since the bleeding 

 volumes and tolerance to hypotension so closely parallel the drug-treated dogs, 

 although the cumulative improvement due to the cooling cannot be excluded. Wlien 

 given in combination, administration of small doses of the drug seems as efficacious 

 as larger dosage in improving tolerance to duration of hypotension, and nearly as 

 effective in the improvement of survival. 



Summary. In an attempt to determine the effect on shock of the various factors 

 employed in "artificial hibernation," namely, hypothermia and the administration of 

 chlorpromazine, these factors were applied separately and in comljination to dogs 

 subjected to "irreversible hemorrhagic shock" by the technique of Fine. 



Two hundred and thirteen dogs were divided into five groups. Fifty animals 

 served as controls; 46 were cooled to 31° C. before shock was induced ; 45 and 20, 

 respectively, were initially treated with 50 and 5 mg. of chlorpromazine and in 38 

 and 14 hypothermia was combined with 50 and 5 mg. of chlorpromazine. respectively. 



Both immediate and ultimate survival were significantly improved by administra- 



