Knights K M, Gourlay G K, Hall P D, Adams J F, Cousins M J
Department of Anaesthesia and Intensive Care, Flinders University of South Australia, Bedford Park.
Br J Exp Pathol. 1987 Oct;68(5):613-24.
The present study extends previous reports of hepatic damage 24 h after halothane anaesthesia in the phenobarbitone pretreated hypoxic rat model by fully characterizing the lesion during the time course of its onset and recovery. Phenobarbitone treated animals exposed to halothane (1% for 2 h in 14% inspired oxygen) were killed 1, 2, 4, 6, 12 and 24 h and 2, 3, 5, 10, 15 and 30 days after commencement of the anaesthetic period. Blood was collected 1 day before the administration of halothane and at the time of killing for determination of serum alanine aminotransferase (ALT), a biochemical index of hepatic damage. Liver tissue was obtained immediately at post-mortem for histological examination. Serum ALT was increased at the end of the anaesthetic period, i.e. 2 h, with peak levels occurring at 12-24 h and remaining elevated for 3 days after exposure. Minor changes in liver histology were evident at 2 h in 50% of the animals and by 6 h all animals had mild hepatic injury. The extent of the necrosis was maximal at 24 h and this was sustained until 3 days. By 5 days after exposure minimal evidence of liver damage was observed and animals killed at 30 days had morphologically normal livers. Elevation of serum ALT or changes in liver histology were not observed in other treatment groups. The early onset of damage at 2-6 h is in keeping with direct hepatotoxicity associated with the biotransformation of halothane.
本研究扩展了先前关于在苯巴比妥预处理的低氧大鼠模型中，氟烷麻醉24小时后肝损伤的报告，通过在损伤发生和恢复的时间过程中全面描述损伤情况。将接受苯巴比妥治疗的动物暴露于氟烷（在14%吸入氧中1%，持续2小时），在麻醉期开始后的1、2、4、6、12和24小时以及2、3、5、10、15和30天处死。在给予氟烷前1天以及处死时采集血液，用于测定血清丙氨酸转氨酶（ALT），这是肝损伤的生化指标。死后立即获取肝组织进行组织学检查。血清ALT在麻醉期末即2小时时升高，在12 - 24小时达到峰值水平，并在暴露后持续升高3天。50%的动物在2小时时肝脏组织学出现轻微变化，到6小时时所有动物均有轻度肝损伤。坏死程度在24小时时最大，并持续到3天。暴露后5天时观察到肝损伤的证据最少，在30天处死的动物肝脏形态正常。在其他治疗组中未观察到血清ALT升高或肝脏组织学变化。2 - 6小时时损伤的早期发生与氟烷生物转化相关的直接肝毒性一致。
