METABOLISM AND DETOXIFICATION— GRAY, RUECKERT axd RINK 233 



corresponding decrease in the binding of morphine. Furthermore, in Hght of the 

 reported fact that thiopental uncouples oxidative phosphorylation"- ^* and generally 

 reduces cellular respiration, we have another mechanisni for slowing the conjuga- 

 tion system of morphine. 



In a similar manner, the increase in the biologic half -life of the thiopental at 

 24° C. may also be the result of the decrease in the respiration of the liver and the 

 inability of the organ to carry out its oxidative processes, normally. It has been 

 shown for dialkyl1)arbituratcs,^'^ for thiobarbiturates^" and barbiturates generally" 

 that the detoxification is brought about by oxidative processes mainly in the liver. 



The effect of the temperature change on the urea production by the liver is also 

 quite marked. The average urea N production at 37° C. was 11.48 ±0.88 mg./hr./ 

 100 gm. liver while at 24° C. it was 7.52 ±0.92 mg./hr./lOO gm. liver. These data 

 were significant at the 2.5% level using the "t" test. MacKenzie and du Vigneaud^^ 

 have shown that the carbon for urea formation arises from respiratory CO2. 

 Ratner and Pappas^^ demonstrated that the "ornithine cycle" required ATP and a 

 mechanism for maintaining the level of ATP, i.e., the oxidative citric acid cycle. 

 In view of decreased respiration resulting in decreased CO2 production and oxida- 

 tive metabolism, the observed decrease in urea production is not surprising. 



Summary. A liver perfusion apparatus with closed gas system providing a 

 means of measuring oxygen uptake volumetrically has been descriljed. The effect of 

 hypothermia on oxygen uptake, carbon dioxide production, morphine and thiopental 

 detoxification, and bile formation in the isolated perfused rabbit liver was observed. 

 Also, the effect of thiopental on morphine conjugation was followed. It is believed 

 that the alterations in metabolic activity observed in vitro with liver perfusion can 

 be attributed to the effect on respiration and oxidative phosphorylation. 



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