EXPERIMENTAL OBSERVATIONS ON THE INFLUENCE OF 



HYPOTHERMIA AND AUTONOMIC BLOCKING AGENTS 



ON HEMORRHAGIC SHOCK* 



ROBERT C. OVERTON and MICHAEL E. De BAKEY 



As a result of the pioneer work of Bigelow,-"^^ the efficacy of general body hypo- 

 thermia in obviating the ischemic consequences of acute circulatory interruption has 

 been widely documented.-- "• ^«' ^'' "• -'' -"' *'- '°' ''• '*• ''' "'• '*■ <='• "^ More recently 

 the concept has been advanced of the state of "artificial hibernation," mediated by 

 the combination of hypothermia and certain autonomolytic drugs, in which the 

 organism is believed to be resistant not only to acute total ischemia, but also to the 

 v^ide range of nocuous stimuli which lead to traumatic and hemorrhagic shock,*'' '- 

 14, 16, 17, 23, 26, 37. 38, 40, 41, 43-46, 49, CO, 70 Broad claiuis have been made, particularly by 

 French investigators, for this concept and its clinical applications, extended even to 

 its administration to battle casualties in Vietnam. ^^' ^°' *"• ^- Their method involves 

 use of body cooling together with a "lytic cocktail" of certain drugs, of which 

 chlorpromazine seems to be the most important.-' Highly significant as the French 

 work may be, the picture is obscured by the polytherapy employed. It seemed im- 

 portant, therefore, to investigate the problem by a carefully controlled study 

 directed toward ascertaining the significance of the various factors involved in the 

 French protocol. 



Because of considerable experience in the study of "irreversible" hemorrhagic 

 shock by the method of Fine,-""' ^^ it was considered desirable to employ this shock 

 preparation and to investigate the effects of hypothermia alone, chlorpromazine 

 alone, and a combination of these two factors on the course of the shock experiment. 



Method. The procedure employed in the production of shock was essentially 

 similar to that previously described. ^^ Healthy, afebrile mongrel dogs, averaging 

 14.5 kg. in weight, were bled via the femoral artery into an elevated reservoir 

 adjusted at such a height that the blood pressure equilibrates at 30 mm. of mercury. 

 The bleeding volume reached a maximum usually in about one hour ; thereafter, 

 as the animal's compensation failed, blood was gradually and spontaneously "taken 

 back" in order to maintain the blood pressure at 30 mm. of mercury. After 40 

 per cent of the maximum volume had thus been taken back, the remainder was 

 rapidly retransfused. If this "40 per cent end-point" was not reached in eight hours, 

 the experiment was arbitrarily terminated by retransfusion. Although after re- 

 transfusion the animals appeared temporarily improved, in our experiments the 

 mortality from this shock preparation has averaged over 90 per cent. In addition 

 to the survival rate, the dog's response to the experiment and to any therapy em- 

 ployed was gauged by the maximum bleeding volume in cubic centimeters per 

 kilogram and also by the duration of hypotension necessary to attain the end-point. 



In both Fine's original work and our previous studies, a local anesthetic was used. 

 In the present study, because of the hypothermia and the necessity for obviating 



* Supported in part by a grant from the Research and Development Division, Department of 

 the Army ; and by the Cora and Webb Mading Fund for Surgical Research, Department of 

 Surgery, Baylor University College of Medicine, Houston, Texas. 



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