PART I 



SOME CONSIDERATIONS OF PHYSIGOGHEMIGAL FACTORS 



IN HYPOTHERMIA 



DUGALD E. S. BROWN 



A consideration of physicocheniical factors in hypothermia is a complex assign- 

 ment. The concept of homeostasis, so well developed by the late Prof. Cannon 

 and stemming- from Claude Bernard's vision of the milieu interior, is sufficient to 

 give anyone a conservative view on the direct role of physical chemistry in hypo- 

 thermia. I am honored at being given this opportunity to open problems for con- 

 sideration, but I am approaching this assignment chiefly as a physiologist with a 

 strong interest in physicocheniical biology. 



The regulation of intra-animal affairs and the maintenance of homeostasis, in 

 the final analysis, rests at the cellular level. If the cardiac output and the chemical 

 composition of the blood are sufficient to meet the cellular re(|uirements. the regula- 

 tory mechanisms will remain effective and the survival of the animal will be assured. 

 On the other hand, when the rate of oxygen utilization exceeds the rate of oxygen 

 transport, cellular activities are reduced and regulation is impaired. 



In induced hypothermia, the low temperature slows the rates of all processes and 

 modifies the action of metabolites and other substances. This in itself is not neces- 

 sarily harmful, as shown by the true hibernator. but will become disastrous as soon 

 as anoxia and chemical imbalance begin to develop. The excellent experiments of 

 Gollan ct al. ( 1955) where dogs, provided with an adequate composition and circula- 

 tion of blood by artificial means, survived cooling to 1.5° C, point directly to cir- 

 culatory failure as the limiting condition in hypothermia with anoxia and chemical 

 imbalance as primary agents modifying the activity of the regulatory cells. 



The basic physicocheniical considerations in hypothermia thus relate to the laws 

 governing the dependence of cellular activities and their enzymatic reactions on tem- 

 perature, ions, metal )olites and drugs. Of particular importance are such cellular 

 phenomena as excitability, rhythmicity and contractility. In regulating the oxygen 

 transport these can act interdependently, since their specific rates are set at comple- 

 mentary levels. When the temperature is lowered, the rates are reduced in accord- 

 ance with the temperature coefficients of the respective processes. In such an inter- 

 dependent system its effectiveness at any temperature depends on the actual relative 

 rates of the processes and on their temperature coefficients. 



In both the true hibernator and the non-hibernator there is every reason to expect 

 comparable values for the temperature coefficients of the cellular reactions. For 

 several hundred processes, including rates of diff'usion, cardiac rhythms, and numer- 

 ous enzyme reactions, the Arrhenius U. values range from U. 3.000 to 25.000 with a 

 large number of processes grouped at U. 6,000, 12.000 and 16.000 (Morales. 1947). 



In terms of the temperature coefficient, or Q,o. these are grouped at Qio 1-0. 

 2 and 3, thus indicating that the rates of the reactions involved would increase in 

 this proportion for a rise in temperature of 10° C. or. in relation to hypothermia, a 



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