Genetic Predisposition to Liver Damage after Halothane Anesthesia in Guinea Pigs

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Abstract
Three 4-hr normoxic (21% oxygen) exposures to 1% halothane administered 3 days apart were associated with elevations in serum alanine aminotransferase (ALT) activity in four of 20guinea pigs after the initial and third exposures. Serum alanine aminotransferase values were not measured after the second anesthetic. Susceptibility was defined as an ALT level greater than 300 IUIL after halothane. Nonsusceptible animals, that is, animals without significant increases in ALT values after halothane, remained nonsusceptible after reexposure. Serum alanine aminotransferase values after the first and third anesthesias were significantly correlated (rs = 0.86, P < 0.001). Two exposures of another 30 guinea pigs at a 5-week interval resulted in high elevations of ALT in the same eight animals after both anesthetics. In contrast, after an initial exposure nonsusceptible animals remained nonsusceptible upon reexposure. Serum alanine aminotransferase levels after the first and second anesthetics were significantly correlated (rs = 0.85, P < 0.001). The proportion of first generation (F1) males with elevated ALTs whose parents were susceptible to halothane hepatotoxicity (HH) was significantly higher than the pro-portion of males with elevated ALTs in a random group of 90 males ( P < 0.005). First generation males and females of nonsusceptible parents had ALTs within the normal range after halothane exposure. These studies suggest that in the guinea pig genetic predisposition is a n important determinant of susceptibility to HH, although other contribution factors are not excluded.