236 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



ferent distribution spaces (or fluid compartments, if you prefer). Going on, how- 

 ever, to transfer problems, I do have information on what I beUeve is the simplest 

 transfer process in the liver, the irreversible removal from the blood of an inert 

 radiocolloid by the reticuloendothelial cells of the liver. We have studied P^-- 

 labelled CrPOi colloid,*' ^ and have shown that three factors determine the rate 

 at which this process occurs : the mean transit time of blood through the liver, the 

 surface to volume ratios of the hepatic blood channels, and the basic rate of the 

 uptake reaction 



CrPOi ( blood )^CrP04 (fixed), 



or, if you prefer, the probability of the micelles' sticking to the surface of a Kupf- 

 fer's cell when they come in contact with one. Reducing the perfusion temperature 

 on the whole tends to lengthen transit time at any given perfusion pressure, as you 

 will readily perceive if you consider what we discussed in relation to hemodynamics. 

 Since I do not know yet what changes in liver blood volume result from cooling, 

 I cannot discuss the surface to volume ratios beyond venturing an opinion that 

 changes due to the temperature here are likely to be very small. Thus, any major 

 changes in CrP04 extraction due to cooling should reflect primarily a modification 

 of the rate of the basic reaction. In fact, lowering the perfusion temperature 

 markedly decreases the efficiency of CrPOi uptake, especially at perfusion rates 

 above the physiological value of 1 cc./g. /minute. The dependence of extraction 

 efficiency upon temperature at a constant perfusion rate is shown in figure 1, the 

 results indicating a molar activation energy of 15,400 cal. for this process. While 

 data are not yet complete regarding the dependence of extraction efficiency upon 

 perfusion rate at various temperatures, results to date are in accord with the hemo- 

 dynamic picture given above. 



Figure 2 illustrates, by means of a typical protocol, some of the other changes 

 in liver function resulting from lowering of perfusion temperatures below the 

 normal 38° C. Blood glucose levels are reduced under those conditions, although 

 the resultant level is not a monotonous function of temperature: the blood glucose 

 levels attained at 30° invariably have been found lower in the isolated liver prepara- 

 tion, than those reached at 25° C, as well as being lower than those obtaining at 

 38° C. Concerning the mechanism of this response little can be said at the moment 

 beyond the fact that it is apparently fully reversible. Glycogen concentrations in 

 preparations cooled and rewarmed do not dift'er significantly from those found in 

 preparations maintained tliroughout at 38° C. We are planning experiments with C^* 

 glucose to estal)lish whether the fall of blood glucose levels reflects increased glyco- 

 gen deposition, decreased glycogenesis, or an unlikely increase of glucose utilization 

 at the lower perfusion temperatures. 



Bile flow decreases dramatically with cooling. While there is some variation 

 from preparation to preparation, the mean relative decrease of bile flow with per- 

 fusion temperature once again obeys an e([uation of the Arrhenius type over the 

 range from 17 to 38° C. Calculated activation energy here is 33,900 cal. This value 

 is close to that obtained for our strain of rats in invo, using surface cooling under 

 sodium pentobarbital; for another strain of rats, however, Kalow'' reported values 

 yielding an Arrhenius energy closer to 15,000 cal. It remains to be established 



