230 INFLUENCE OF TEMPERATURE ON BIOLOGICAL SYSTEMS 



shortens life, and that reduction of body temperature in this situation 

 would prolong the period during which resuscitative measures would be 

 effective? Since the Qio of most living processes is between two and three, 

 reduction of 20°C in body temperature might increase anoxic survival 

 by as much as four times. In addition, since the newV)orn mammal, 

 including man, is essentially poikilothermic (23, 66, 91, 62, and others), 

 jn-oblems of activation of homeostatic mechanisms which might arise in 

 the adult would be minimized. Finally, it became obvious early in our 

 experiments that, since these homeostatic mechanisms are completely 

 blocked by anoxia, hypothermia should likewise prove effective in pro- 

 tecting the adult from the effects of asphyxia. The results of experiments 

 designed to test the validity of these concepts constitute the main subject 

 matter of this report. As a result of subsequent extension of the scope 

 of the problem to include other means of reduction of metabolism and 

 attempts to increase energy sources, the latter part of this paper will 

 concern itself with the effects of temperature combined with these agents. 

 An ideal laboratory animal for this study would be born in large litters 

 at the same stage of development as the human. Since this animal has 

 not come to our attention, it was necessary to compromise. Among the 

 common laboratory animals the mouse, rat, hamster and rabbit are 

 delivered in a far less and the guinea pig in a more advanced stage 

 than the human baby. The guinea pig was selected for intensive study 

 because it is the most sensitive to oxygen lack (71) and presumably any 

 treatment which proved beneficial should be more rather than less effective 

 for man. In addition, the important studies of Windle and of Becker have 

 demonstrated that in this species asphyxia at birth produces the same 

 spectrum of behavioral changes as has been observed in man (185). Their 

 resuscitated animals exhibited a variety of neurological symptoms includ- 

 ing spastic and flaccid paralyses, ataxias, tremors, twitchings, epileptiform 

 seizures and somnolence. Histological studies of the brains disclosed edema 

 and multiple capillary hemorrhages which appeared within 2 hours and 

 disappeared within 5 days. Neuronal damage was visible in all animals 

 up to 21 days and permanent structural changes were found in two- 

 thirds of the severely asphyxiated animals (186). Tests of the learning 

 ability of animals with no overt behavioral evidence of permanent damage 

 showed that asphyxiated animals required far more trials to learn a 

 maze and after only 2 weeks' rest had largely forgotten what they had 

 learned (30, 31). Hurder has reported similar results in rats (94-96). 



EARLY USES OF HYPOTHERMIA 



The earliest use of hypothermia as an analgesic is lost in unrecorded 

 antiquity. Undoubtedly its ability to deaden pain was discovered and 



