232 



PHYSIOLOGY OF INDUCED HYPOTHERMIA 



off very rapidly. These measurements were made at the venous outflow of the liver. 



Whereas the level of free morphine rises extremely rapidly in the hepatic out- 

 flow at Z7° C, there is a very definite slowing of the mixing time at 24° C. as 

 illustrated in figures 4 and 5. This may well be the result of the flow of the per- 

 fusion fluid which was decreased by about 25% but with a large variation at both 

 temperatures. 



There was a three to six minute delay in the appearance of the bound morphine 

 suggesting that morphine is held briefly by the hepatic cells while being conjugated. 

 Further support of this possibility was observed by the rise in level of bound mor- 

 phine in the hepatic veinblood for 10 to 15 minutes after all free morphine had 

 been removed from the "arterial" blood. 



The rate of bile formation at ^1° C. was two to four times that observed at 24° C. 



These observed metabolic effects may well be the result of the inability of the 

 liver to form the glucuronide of morphine.^" It has been recently demonstrated^^' ^- 

 that the glucuronide is formed through the formation of uridine diphosphate glu- 

 cose. In view of the markedly reduced respiration of the liver as a result of the 

 hypothermia, it is not unexpected that this mechanism is slowed down with a 



(o 80 



< 



37°c. 



M.S. 50mg, 



300 



320 340 



MINUTES 



360 



Fig. 5. — Morphine metabolism by perfused liver at 'i'l° C. 



