Baden J M, Serra M, Fujinaga M, Mazze R I
Department of Anesthesia, Stanford University School of Medicine, California.
Anesthesiology. 1987 Nov;67(5):660-4. doi: 10.1097/00000542-198711000-00008.
A rat model was used to determine whether the metabolism of halothane is changed in the presence of cirrhosis and whether exacerbation of liver dysfunction is correlated with such a change. Cirrhosis was produced by gavaging enzyme-induced male Wistar rats with carbon tetrachloride in corn oil once weekly for 12 weeks. Control rats received corn oil only. After a 3-week period without treatment, blood and urine were collected from each rat for determination of background levels of inorganic fluoride, bromide, and trifluoroacetic acid (halothane metabolites) and for assessment of liver function. Rats were then anesthetized with 1.05% halothane in 50% oxygen for 3 h. Following anesthesia, serial blood and urine samples were taken to monitor halothane metabolism and liver function. No differences were observed between cirrhotic and non-cirrhotic rats in serum levels and urinary excretion of halothane metabolites. However, serum levels of SGOT and SGPT were significantly increased about 1.5-fold in the noncirrhotic group and about 2.5-fold in the cirrhotic group after anesthesia. The increased levels observed in the cirrhotic group were significantly greater than in the noncirrhotic group. The results imply that the exacerbation of liver dysfunction after halothane anesthesia is most likely related to an indirect effect, such as change in liver blood flow, rather than to toxic metabolites.
采用大鼠模型来确定在肝硬化存在的情况下氟烷的代谢是否发生变化，以及肝功能恶化是否与这种变化相关。通过每周一次给酶诱导的雄性Wistar大鼠灌胃溶于玉米油的四氯化碳，持续12周来制造肝硬化。对照大鼠仅接受玉米油。在未经治疗的3周后，从每只大鼠采集血液和尿液，用于测定无机氟化物、溴化物和三氟乙酸（氟烷代谢物）的背景水平，并评估肝功能。然后用含1.05%氟烷的50%氧气麻醉大鼠3小时。麻醉后，采集系列血液和尿液样本以监测氟烷代谢和肝功能。在氟烷代谢物的血清水平和尿排泄方面，肝硬化大鼠和非肝硬化大鼠之间未观察到差异。然而，麻醉后，非肝硬化组血清谷草转氨酶（SGOT）和谷丙转氨酶（SGPT）水平显著升高约1.5倍，肝硬化组升高约2.5倍。肝硬化组观察到的升高水平显著高于非肝硬化组。结果表明，氟烷麻醉后肝功能恶化很可能与间接效应有关，如肝血流变化，而非与有毒代谢物有关。
