Comparison of the Requirements for Hepatic Injury with Halothane and Enflurane in Rats

Publisher Website
Google Scholar
Abstract
A rat model of cnflurane-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°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 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 hepatotoxicity 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. Thus the HH model appears to act via a bioactiva- tion/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.