Halothane hepatotoxicity in guinea pigs

A recently reported animal model of halothane-associated hepatotoxicity in males of a colored strain of guinea pig was further characterized as to possible sex and strain specificity in outbred albino Amana, inbred albino Hartley, inbred colored strain 2, and inbred colored strain 13 guinea pigs. Exposure to 1% halothane for 4 hr in 21% O₂ proved to be hepatotoxic in both sexes. Forty-eight hours after halothane exposure fatty vacuolization of hepatocytes was present in all animals. Histologically identifiable hepatic necrosis occurred in 60% of the guinea pigs exposed, along with concomitant increases in SGPT. Approximately one half of these responding animals had extensive centrilobular necrosis, which was still present 96 hr after halothane exposure. Females of the inbred strain 2 and males and females of strain 13 were the most susceptible to halothane-induced hepatic necrosis whereas the inbred Hartley strain was almost totally refractory to necrosis. Outbred Amana and male inbred strain 2 animals exhibited an intermediate hepatotoxic response. Comparison of the halothane-associated hepatic lesion with that induced by anoxic/ischemic mechanisms, (exposure to low (8%) oxygen during 1.7% enflurane anesthesia) showed obvious differences in the morphology of the hepatic necrosis and the apparent time course of lesion development. This guinea pig model of halothane-associated hepatotoxicity appears to be superior to previous animal models in that no pretreatment of the guinea pigs is required, both sexes are affected, and the resulting hepatic lesion is more persistent.