240 



PHYSIOLOGY OF INDUCED HYPOTHERMIA 



slowing down gradually as the dye accumulates in the liver. At temperatures below 

 38° C. two changes supervene: the efficiency of extraction at the start decreases 

 and the exponential portion of the disappearance curve is shortened, extraction 

 efficiency falling off after extraction of a much smaller fraction of the injected 

 dose. Excretion of dye in the liver into bile apparently is affected only to the degree 

 that bile flow is delayed. As shown in figure 4, peak concentrations of BSP (or of 

 its derivatives) in the bile are unaffected by cooling to 29° C. at least. Figure 5 

 finally shows that initial BSP extraction efficiencies are far less affected by cooling 

 the organ than is the bile flow or, by implication, the rate of re-excretion of the 

 dye into bile. While a discussion of these results (which have important bearing 

 on the problem of BSP transfer mechanisms, and the coupling of uptake and 

 excretion of this dye) is beyond the scope of this communication,^ it seems proper 

 to point out that once again the changes in liver function in hypothermia resemble 

 remarkably those seen in subtotal bile stasis. 



Looking back over what has been reported here, the effects of hypothermia on 

 liver physiology seem to fall into three categories: circulatory effects, dominated 

 by the change of blood viscosity with temperature ; certain functions which fall off 

 in accordance with the classical Arrhenius relation, and wdth varying activation 

 energies (bile flow, CrPOi colloid uptake) ; and, finally, certain complex effects 

 manifesting imbalance of various metabolic chains in the hypothermic organ. 

 Examples of this last group are the equilibrium levels of blood glucose, the indica- 

 tion of a critical zone for non-recovery of certain functions, and the phenomena 

 tentatively grouped together as reflecting hypothermic bile stasis : the overshooting 

 of bile flow, "freezing in" of choleresis, BSP uptake curves. It is our feeling that 

 exploration in this third group of phenomena is most likely to lead to answers to 

 the problems of interest to us all in relation to the survival and recovery of the 

 homeothermic organism subjected to hypothermia. 



From another point of view, the relations between blood flow and bile flow in 

 the hypothermic preparation (figure 3) are an illustration of the protection afforded 

 against ischemia by hypothermia, and to those of us interested in liver physiology 

 may suggest a number of extension experiments in relation to the action of noxious 

 agents upon this organ and their possible counteraction l^y regional hypothermia. 



20 40 60 80 



MINUTES AFTER INJECTION 



'/o RECOVERY 



OF BSP 



lOO 



50 75 100 



% RECOVERY OF INJECTED DYE 



20 40 60 



MINUTES AFTER INJECTION 



Fig. 4. — Relations between biliary BSP excretion, time, and per cent recovery of injected dose, 

 following injection of two doses of 5 mg. BSP each, one at 38'' C. and one at 29° C. per- 

 fusion temperature. 



