2 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



decrease in the same proportion. In general, the rates of metaboHc and rhythmical 

 processes exhibit a Qio of 3, the rates of contraction a Qio of 2, and the rates of 

 most physical processes such as diffusion, a Qio of 1. As a result, when the tempera- 

 ture is lowered the rates of metabolic and rhythmical processes decrease two to three 

 times as much as the rate of diffusion of the metabolites. 



In both the hibernator and non-hibernator it would be expected that the tempera- 

 ture coefficients for identical processes would be the same. The factor contributory 

 to the ready survival of the hibernator would be that the reaction rates of the vari- 

 ous cellular processes have a better relative setting at 38° C. Thus on cooling, al- 

 though the rates decrease, the relative values are sufficient for the over-all effective- 

 ness of the system. 



In the non-hibernator it appears that the rate setting of the processes is quite 

 different. The end result is that, although the Qio's are the same, a lowering of the 

 temperature reduces the rates of certain reactions to a level where they can no longer 

 contribute effectively as members of an interdependent reaction system. 



Considering that such a system is acting on events within cells, it could lead, for 

 example, to cessation of the cardiac rhythm at 13° C. in the dog, whereas the beat 

 of the hamster could continue at a much lower temperature. At the systemic level, 

 acting between the heart and the nervous system, it could interfere with the nervous 

 regulation of the heart. 



In accordance with the foregoing, the control of induced hypothermia would rest 

 on the extent to which the rates of cellular processes and their temperature coeffi- 

 cients could be controlled. The extent to which this could be accomplished naturally 

 depends on a sound understanding of the cellular phenomena involved and the laws 

 governing their susceptibility to temperature, ions and drugs. 



The most significant physicochemical development bearing upon intracellular 

 enzymes stems from the studies of F. H. Johnson and co-workers * on bacterial 

 luminescence. In an extensive investigation of the luminescence reaction in vivo, its 

 dependence on temperature, pressure and various chemical agents was established 

 and the kinetics described in terms of the Glasstone-Eyring theory of absolute reac- 

 tion rates. Recently the essential enzymatic proteins were isolated from the bacterium 

 Achronwbacter fischeri and light emission found to occur in the presence of FMN 

 (flavin mononucleotide), reduced DPN (dihydrodiphosphopyridine nucleotide), 

 and palmitic aldehyde. When this system was studied in relation to temperature, 

 pressure and inhibitors, it was found to behave similarly to the system in vivo 

 (Strehler and Johnson, 1954). 



For many years it has been the hope of both physiologists and physical chemists 

 that a specific cellular process, enzymatically controlled, could be duplicated by the 

 isolated enzymatic proteins in vitro. It seems that this is being approximated in bac- 

 terial luminescence. Assurance is thus given that the physicochemical analyses of 

 intracellular reactions can provide valuable information on the properties of the 

 underlying enzymatic reactions which control the wide spectrum of cellular reactions. 

 In relation to the regulation of hypothermia and its control, there is thus a good 



* An extensive treatment of the physical chemistry of enzymatic and cellular processes in rela- 

 tion to temperature, pressure and chemical agents will be found in F. H. Johnson, Henry Eyring 

 and M. J. Polissar : The Kinetic Basis of Molecular Biology, John Wiley and Sons, Inc., New 

 York, 1954. 



