REVIEW AND APPRAISAL OF PART III— BROOKS and HOFFMAN 361 



coronary occlusion at low temperatures). It is also possiljle that the effect of age 

 of the animal on tlie response to hypothermia, as well as the reported heneficial 

 effects of liigJi pCC)., in tlie inspired air may both he related to differences in local 

 perfusion of tissues. 



If we consider that, in some instances, tissue perfusion is in certain respects in- 

 adequate we are in a position to ask : What are the direct results of poor perfusion 

 which might give rise to the undesired effects of hypothermia (i.e., fibrillation and 

 high-temperature asystole)? We should consider the following factors: 



1. Anoxia (local). 



2. Hypercapnia ( local ) ±:5and pH. 



3. Electrolyte imbalances : K* ; Na^'' ; Ca^* ; H\ 



4. Other effects on metabolic activity of cell and cell memlirane. 



5. Dissimilar effects in various regions or tissues. 



Also, the possibility should be considered that at certain critical stages of hypo- 

 thermia, norepinephrine and/or epinephrine are released (Hume, etc.) or unusual 

 autonomic nerve discharges occur as a part of the nonshivering compensatory 

 mechanism (Keller). Certainly a combination of excitatory action and depression 

 would tend to favor development of arrhythmias (Brooks, et al.). Keller's work 

 constitutes a contribution to such studies but it is not as yet sufficiently extensive. 



There is ample evidence for the possible role of each, any, and all of these 

 factors from the reports of various investigators. 



Hegnauer says that fibrillators are identified by S-T segment changes, by low 

 diastolic thresholds and by positive Ca and negative K and H ion balances of myo- 

 cardium. Taking these statements at face value, what can they imply regarding the 

 underlying mechanisms ? 



The ECG change noted is entirely non-specific. It can be brought on at unusually 

 high temperatures by giving Ca, and abolished at low temperatures by giving K, 

 P04=, or changing pH ; and yet it may persist in spite of pH reversal, and may be 

 brought on at normal temperature by high pCOj. It can be caused by local injury 

 or asymmetrical cooling or anoxia, etc. 



If this ECG finding has any significance it is that of local differences in the 

 condition of the myocardium with respect to the time-course of repolarization. In 

 the simplest case, it suggests that in some areas the plateau of the action potential 

 has been lost in certain fibers but retained in others. Such a change in the plateau 

 might result from anoxia, ions (Ca|, K|), perhaps from changes in pCOo amd 

 pH. At any rate, any of these could be an effect of local perfusion deficiency. Not 

 to be ignored, however, is the effect of unequal cooling of the heart, which could 

 give a similar picture if the temperature gradient were great enough. 



Studies of isolated heart fibers have not revealed significant changes in the criti- 

 cal "threshold" potential level. The next possible cause of a lowering of diastolic 

 threshold is a change in resting potential, and it is interesting that studies of single 

 fibers begin to show a drop in resting potential at the same temperature (around 

 25-26°) as that associated with a significant decrease in threshold of potential 

 fibrillators. 



Again, however, we cannot exclude inadequate perfusion as a contributing factor, 



