360 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



expected end result, and spontaneous rhythmicity will cease at different tempera- 

 tures in different parts of the myocardium (Brooks, Hoffman). If the body temper- 

 ature is in the range of 20-10° C. when asystole supervenes, long periods (25 -|- 

 minutes) of complete lack of perfusion can be tolerated by the heart without any 

 evidence of damage (Gollan, Lewis, others). Furthermore, most studies indicate 

 that, prior to the advent of asystole the cardiac output, in terms of O2 flow, is at 

 all times more than adequate. Thus, in the simplest situation, there seems to be no 

 problem with respect to hypothermia (Dammann and Mviller) as, indeed, is actually 

 the case in studies of isolated cardiac tissues (Hoffman) and as is always seen in 

 hibernators and sometimes in non-hibernators. When difficulties are encountered in 

 hypothermic mammals, they might thus be divided into two major areas : 1 ) the 

 onset of fibrillation at relatively high temperatures (26°— >19° C.) when the body 

 still requires blood flow and 2) the onset of asystole (a normal and expected 

 result) at too high a temperature, when flow is still required. If we disregard the 

 requirement for hlood flozv, both these happenings (fibrillation and asystole) 

 provide certain surgical advantages (quiet heart, less danger of air embolism with 

 open heart, etc.). 



The problem is thus simplified, at least in superficial analysis, to a search for 

 the factors responsible for onset of fibrillation and asystole at temperatures which 

 are inconveniently high. As a starting point, it is probably easiest to assume that 

 there are multiple factors which may all not always be present and which, in 

 different combinations, can cause trouble. In an analysis of these factors, however, 

 it is immediately apparent that our information is not adequate to permit a full 

 evaluation of each factor. 



Inadequate perfusion. Although studies of A-V Oo differences during hypo- 

 thermia suggest that O2 carried to the capillaries is in excess of tissue requirements, 

 we have no conclusive evidence that oxidative metabolism is normal. Thus the 

 rate of oxidative activity may be depressed to an extent that does not keep up with 

 the other metabolic requirements of the tissue. More important, we have little 

 evidence concerning the adequacy of CO2 removal from tissues. Under certain 

 conditions it is possible that serious local accumulations of CO2 occur in spite of, 

 or even perhaps in part due to the high p02. 



Also to be considered with respect to perfusion is the question of local changes 

 in electrolyte concentration. Poor perfusion of the extracellular spaces of certain 

 cells will result in (1) local changes in electrolyte concentrations differing from 

 those obtaining elsewhere, and (2) an inability to evaluate local electrolyte shifts 

 from a study of plasma electrolyte levels. Finally data on water shifts between 

 plasma, extracellular and intracellular phases are not adequate. 



These findings suggest several areas where added work is required. Information 

 on cellular metabolic activity, local concentrations of CO2 and ions, and local 

 changes in water distribution are needed. It is possible that accurate studies of 

 PO2, by means of the so-called oxygen electrode, would show results similar to 

 those obtained on the cerebral cortex — large differences in p02 of cells near to 

 and far from capillaries. 



The evidence in favor of a perfusion defect is fairly good (Gollan's studies using 

 a pump-oxygenator, and getting no fibrillation, and also his studies of the effect of 



