GENERAL METABOLISAl— HORVATH and SPURR 21 



reasoned that the initial respiratory alkalosis ol)servcd in some of his animals would 

 lower the serum l)icarl)onate content and render the animals more susceptible to the 

 subse([nent respiratory acidosis. Inducing a respiratory acidosis (thereby raising the 

 serum bicarlxjnate) previous to the induction of liypothermia appeared to have a 

 pi-otective effect in a small series of animals. 



McMillan ct alf- agreed that under conditions of circulatory arrest sudden changes 

 in pH might be the cause of ventricular fibrillation." but pointed out that this could 

 not be involved in spontaneous hypothermic ventricular fibrillation since pH and 

 COo content change gradually and not suddenly. Covino and Hegnauer'" found a 

 marked lowering of the ventricular diastolic and minor dip'"''' thresholds, with con- 

 sequent ventricular fibrillation, in hypothermia. They ascribed this to the respiratory 

 acidosis which develops at low body temperatures, since both are threshold effects 

 and ventricular fibrillation could be prevented by maintaining the pH near normal 

 during cooling. 



The respiratory acidosis which develops during hypothermia would therefore 

 appear to be disadvantageous to adequate cardiac functioning. However, changes 

 in pH and blood CO. observed in hypothermia have at least two advantages. De- 

 creased pH tends to counteract the effect of low temperature on the oxygen dissocia- 

 tion curve. Also, the pH and CO2 represent an attempt to compensate for the de- 

 pressing action of low temperature on the respiratory center. Cranston ct al.-'' found 

 that in dogs at rectal temperatures of 25-27° C. there was an essentially normal 

 respiratory response to inhalation of 6 per cent carbon dioxide in air and concluded 

 that the observed plasma increase in CO2 was the result of the action of a function- 

 ing control mechanism. 



BODY WATER 



Relatively little attention has been directed to the question of body fluid shifts 

 which may take place during hypothermia. There have been several isolated observa- 

 tions such as Walther's" report of pulmonary ederoa in rabbits which had been sub- 

 jected to hypothermia and Woodruff's-" mention of cardiac edema in dogs main- 

 tained for long periods at low body temperatures. However, the work of Barbour, 

 McKay and Griffith^^ on monkeys and rats was the first precise approach to the 

 problem. On the basis of observed changes in plasma proteins and chloride they 

 concluded that there was a decrease in plasma volume and concomitant increase in 

 interstitial and intracellular volumes during the initial phases of cooling. They 

 attributed this movement of water into the cells to the increased metabolic rate 

 of the cells which produced a temporary accumulation of metabolites. Upon cooling 

 to 23° C. the entire water shift was reversed. Rodbard et ol.'^^ pointed out that the 

 data obtained on hematocrit and plasma protein concentration in hypothermia could 

 be obtained without associated changes in blood volume. These investigators found 

 only small changes in hematocrit and plasma proteins in chicks and rabbits sub- 

 jected to hypothermia. However, plasma volume (Evan's Blue technique) and 

 thiocyanate space were reduced about 30 per cent in hypothermia. Measurement of 

 extracellular volume by means of inulin revealed no changes in this compartment. 

 Inspection of their technique revealed that the measurements of thiocyanate space 

 had been made either before or after the cooling procedure, whereas the determina- 



