CYTOTOXICITY OF I.V. ANAESTHETIC AGENTS ON THE ISOLATED RAT HEPATOCYTE

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Abstract
The isolated rat hepatocyte model has been used to assess the hepatotoxicity of a number of i.v. anaesthetic induction agents. Ketamine, Althesin and CCI 12923 (minaxolone) all inhibited gluconeogenesis and urea formation from alanine. There was also a decrease in the cell ATP concentration, and a dose-related increase in leakage of LDH. Of these indices of cell toxicity, gluconeogenesis from alanine was found to be the most sensitive. Fifty per cent inhibition of gluconeogenesis for all three agents occurred in the range 150–300 μmol. The effects of these agents on the isolated hepatocyte may be attributed to a primary impairment of mitochondrial function through a change in the ATP concentration. The plasma concentration of anaesthetic agents measured during their clinical use is at least one order of magnitude less than that required to cause 50% inhibition of gluconeogenesis.