Toxicity of Halogenated Volatile Anesthetics in Isoláted Rat Hepatocytes

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Abstract
Suspensions of rat hepatocytes, prepared by a collagenase-based isolation technique, were incubated for 20 or 60 min in the presence of various concentrations of these anesthetics. Toxicity was assessed by measuring the leakage of intracellular K+ and alanine aminotransferase, decrease in the rate of ureogenesis and increase in the lactate: pyruvate ratio. Toxicity measured after 20 min of incubation was dose-related, and the magnitudes of the effects of chloroform and methoxyflurane were approximately equal and significantly (P < 0.01) exceeded that of halothane. Enflurane did not affect K+ or alanine aminotransferase release, even after 60 min of incubation, at which time halothane toxicity was markedly increased (P < 0.002). Enflurane did produce effects on ureogenesis and the lactate:pyruvate ratio, although these were less than those of the other agents. Apparently the toxic effects of halogenated volatile anesthetics measured in this in vitro preparation are of the same comparative order as their clinical hepatotoxic potentials.

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