Sear J W, McGivan J D
Br J Anaesth. 1979 Aug;51(8):733-9. doi: 10.1093/bja/51.8.733.
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 mumol. 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.
离体大鼠肝细胞模型已被用于评估多种静脉麻醉诱导剂的肝毒性。氯胺酮、阿耳法辛和CCI 12923（米那索龙）均抑制丙氨酸的糖异生和尿素生成。细胞ATP浓度也降低，乳酸脱氢酶（LDH）泄漏呈剂量相关增加。在这些细胞毒性指标中，丙氨酸糖异生被发现是最敏感的。所有三种药物对糖异生的50%抑制发生在150 - 300 μmol范围内。这些药物对离体肝细胞的作用可能归因于ATP浓度变化导致的线粒体功能原发性损害。在临床使用期间测量的麻醉剂血浆浓度比引起糖异生50%抑制所需浓度至少低一个数量级。
