Hepatic necrosis caused by halothane and hypoxia in phenobarbital-treated rats.

Abstract

Other studies have indicated that hypoxia enhances the binding of halothane metabolites to components of the hepatic microsomal fraction. The authors pretreated Wistar rats with phenobarbital, 75 mg/kg, daily for four days to induce the hepatic drugmetabolizing enzyme system and subsequently made them hypoxic (FI02 = .08) while they were receiving halothane, 0.6 percent. Centrilobular hepatic necrosis was well developed by six hours following exposure, and early stages of resolution were evident by 48 hours. Hemorrhage occurred within the necrotic areas, and leukocytosis was not prominent. Normal rats or those depleted of hepatic glutathione did not experience hepatic necrosis when made hypoxic and given halothane. Rats receiving halothane in adequate oxygen (Fl02 = 0.50) after phenobarbital pretreatment showed no hepatic necrosis. Plasma fluoride values were normal (