Comparison of the requirements for hepatic injury with halothane and enflurane in rats

R. C. Lind, A. J. Gandolfi, I. G. Sipes, B. R. Brown

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13 Scopus citations


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 adults 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°C, while heating the animals during anesthesia resulted in only a 0.5-2°C 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 CCl4L: 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 vascuolization 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 hepatotoxicity but had little effect on the HH model in both requirements for and type of hepatic injury. Thus the HH model appears to act via a bioactivation/chemotoxic mechanism, whereas models of anesthetic-induced hepatotoxicity that require very low oxygen tensions and heating of the animals during exposure result from a severe hypoxia/anoxia of the liver.

Original languageEnglish (US)
Pages (from-to)955-963
Number of pages9
JournalAnesthesia and analgesia
Issue number10
StatePublished - 1985

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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