Frost L, Mahoney J, Field J, Farrell G C
Storr Liver Unit, Department of Medicine, University of Sydney, NSW, Australia.
Hepatology. 1996 Jan;23(1):80-6. doi: 10.1002/hep.510230112.
To characterize the early events in liver injury produced by halothane, experiments were performed in genetically susceptible guinea pigs 19 hours after halothane exposure. Serum bile acid concentrations were fourfold increased in halothane-exposed animals compared with controls. In isolated perfused liver experiments, livers from halothane-exposed animals did not differ in hepatic oxygen uptake or in perfusion pressure at the end of experiments, but bile flow and biliary bile salt concentrations were reduced. Hepatic calcium content was increased in halothane-exposed guinea pigs compared with controls, and further experiments were performed to explore the reason for this. As determined by infusion of 45Ca to steady-state perfusate concentrations, hepatic calcium clearance was increased in halothane-exposed guinea pigs compared with controls (0.37 +/- 0.06 vs. 0.28 +/- 0.02 mL/min, P < .01). Decreased biliary excretion of calcium was also noted and was entirely attributable to reduced bile flow. However, although decreased excretion contributed to hepatic accumulation of calcium, it was quantitatively less important than enhanced hepatic uptake. As indicated by passage of a bolus of horseradish peroxidase from perfusate into bile, hepatic tight junction permeability was increased five-fold after halothane exposure. It is concluded that cholestasis, as exemplified by reduced bile flow, is an early feature of the liver injury produced by halothane in guinea pigs and is associated with increased tight junction permeability. Although the decrease in bile flow contributes to an early increase in hepatic calcium content, entry of calcium from the perfusion compartment is quantitatively more important.
为了描述氟烷引起肝损伤的早期事件，在基因易感性豚鼠接触氟烷19小时后进行了实验。与对照组相比，接触氟烷的动物血清胆汁酸浓度增加了四倍。在离体灌注肝脏实验中，接触氟烷动物的肝脏在实验结束时肝氧摄取或灌注压力没有差异，但胆汁流量和胆汁中胆汁盐浓度降低。与对照组相比，接触氟烷的豚鼠肝脏钙含量增加，并进行了进一步实验以探究其原因。通过向稳态灌注液中输注45Ca测定，与对照组相比，接触氟烷的豚鼠肝脏钙清除率增加（0.37±0.06对0.28±0.02 mL/分钟，P<0.01）。还注意到钙的胆汁排泄减少，这完全归因于胆汁流量减少。然而，尽管排泄减少导致肝脏钙蓄积，但在数量上不如肝脏摄取增加重要。如通过将一大剂量辣根过氧化物酶从灌注液注入胆汁所示，氟烷暴露后肝紧密连接通透性增加了五倍。结论是，以胆汁流量减少为例的胆汁淤积是氟烷在豚鼠中引起肝损伤的早期特征，并且与紧密连接通透性增加有关。尽管胆汁流量减少导致肝脏钙含量早期增加，但来自灌注区室的钙进入在数量上更重要。
