Comparison of the requirements for hepatic injury with halothane and enflurane in rats.
A rat model of enflurane-associated hepatotoxicity was compared with the halothane-hypoxia (HH) model (adult male rats, phenobarbital induction, 1% halothane, 14% O2, for 2 hr). The enflurane-hypoxia heating (EHH) model involved exposing phenobarbital-pretreated male adult rats to 1.5-1.8% enflurane at 10% O2 for 2 hr with external heating to help maintain body temperature. Exposure to either anesthetic without temperature support led to a decrease in body temperature of 7-9 degrees C, while heating the animals during anesthesia resulted in only a 0.5-2 degree decrease. Reducing the oxygen tension to 10% O2 combined with heating the animals during exposure produced significant decreases in the oxidative metabolism of both halothane and enflurane as compared to exposures of 14% O2. The same conditions also caused a significant increase in the reductive metabolism of halothane, indicating that a severe hepatic hypoxia or anoxia occurs during anesthesia at 10% O2 with external heating. The time course of lesion development in the HH model paralleled results obtained with an oral dose of CCl4: gradual progression of necrosis up to 24 hr. EHH resulted in a classic hypoxic/anoxic injury with elevated serum glutamate pyruvate transaminase values and a watery vacuolization of centrilobular hepatocytes immediately after exposure. The HH model required phenobarbital pretreatment of the rats for expression of hepatic injury; EHH did not. Heating of the animals during anesthesia exposure was necessary for enflurane-induced hepatoxicity but had little effect on the HH model. Exposure to 5% O2 without anesthetic mimicked EHH in both requirements for and type of hepatic injury.
D000769:Anesthesia, Inhalation / Q000009:adverse effects*; D000818:Animals; D001711:Biotransformation; D001831:Body Temperature; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004737:Enflurane / Q000378:metabolism / Q000633:toxicity*; D005459:Fluorides / Q000097:blood; D006221:Halothane / Q000378:metabolism / Q000633:toxicity*; D006358:Hot Temperature; D000860:Hypoxia / Q000139:chemically induced; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008954:Models, Biological; D010100:Oxygen; D010634:Phenobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014269:Trifluoroacetic Acid / Q000097:blood
D004737:Enflurane; D002251:Carbon Tetrachloride; D014269:Trifluoroacetic Acid; D005459:Fluorides; D010100:Oxygen; D006221:Halothane; D010634:Phenobarbital