Toxicity of halothane in guinea pig liver slices

Guinea pigs have proven to be a reliable model of halothane associated hepatotoxicity. An in vitro system with Hartley male guinea pig liver tissue was designed to assess the toxicity of halothane and other volatile anesthetics in the target organ. Precision-cut guinea pig liver slices (250-300 microns) were incubated in sealed roller vials containing Krebs-Henseleit buffer (plus vitamins, amino acids, glutamine, gentamycin) at 37 degrees C, under 95%, 21% and 5% O2/CO2 atmospheres. Halothane (10-15 microliters) was injected through a Teflon septa cap on a filter paper wick and vaporized. Viability of the slices was monitored by measuring intracellular K+ content which was maintained under 95% O2 up to 24 h. A dose- and time-related decrease in intracellular slice K+ by 1.9, 2.1, 2.7 mM halothane in the media was observed. At 2.7 mM halothane a direct physio-chemical effect may be occurring since incubating liver slices from allylisopropyl-acetamide-treated animals did not protect against the drop in intracellular K+. Concentration/time responses of halothane, d-halothane, enflurane, isoflurane and sevoflurane were compared. Sevoflurane had no effect on the liver slice K+ content up to 24 h while the other anesthetics caused the following rank-order decrease in intracellular K+ content: halothane greater than isoflurane and enflurane greater than d-halothane. Precision-cut cultured guinea pig liver slices offer a system where the target tissue for intoxication by anesthetics can be examined for its susceptibility and mechanism of intoxication.