A Study about Effects of Anesthesia on Hepatic Circulation, Oxygen Metabolism, Intra-cellular Ca^<++> Mobilization and Liver Injury

1)观察了氟烷、异氟烷和七氟烷在犬低氧血症和肝切除时对肝脏血流量(HBF)、氧代谢(Hom)和能量代谢(HEC)的影响。异氟醚和七氟烷维持HBF、HOM和HEC的效果好于氟烷。这些结果表明，除非在严重缺氧条件下，异氟醚或七氟醚不会引起HOM失衡所致的肝损伤。2)观察比格犬芬太尼麻醉下体外循环(CPB)期间HbF和Hom的变化。CPB期间将芬太尼剂量增加到50µg/kg/h可降低HbF和Hom，而10µg/kg/h的芬太尼对HbF和Hom的影响最小，灌注率在CPB前主动脉血流量的80%以内。CPB期间大剂量芬太尼合并低氧血症可能导致肝损伤。3)器官灌流受血管周围平滑肌收缩和松弛的调节。一般来说，这种调节受一氧化氮(NO)的产生和形成的影响，在肝窦中也是如此。在肝脏中，由结构型一氧化氮合酶(CNOS)合成的NO被认为控制肝窦微循环。CNOS在合成NO过程中需要钙离子，因此与细胞内游离钙离子浓度密切相关。我们建立了一种新的高灵敏度的测定全血中与cNOS依赖的NO有关的化合物的新方法，并正在研究NO产生与细胞内Ca~(++)&Gt；动员和麻醉剂降低HBF之间的关系。

1) Effects of halothane, isoflurane and sevoflurane on hepatic blood flow (HBF), oxygen metabolism (HOM) and energy carge (HEC) were investigated in mongrel dogs during hypoxemia or hepatologectomy. Isoflurane and sevoflurane maintained HBF,HOM and HEC better than halothane. These results indicate that liver injury based on imbalance of HOM would not be induced by isoflurane or sevoflurane except under severe hypoxic condition. 2) HBF and HOM were also investigated in beagles during cardiopulmonary bypass (CPB) with fentanyl anesthesia. Increasing the dose of fentanyl to 50 mug/kg/h during CPB decreased HBF and suppressed HOM,while 10mug/kg/h of fentanyl produced minimal effects on HBF and HOM,so far as perfusion rate was within 80% of aortic blood flow of pre-CPB value. A large dose of fentanyl during CPB combined with hypoxemia could possibly cause liver injury. 3) Organ perfusion is regulated by contraction and relaxation of smooth muscles around vessels. In generally speaking, this regulation would be influenced by nitric oxide (NO) production and formation, and also same in hepatic sinusoids. In the liver, NO synthesized by constitutive NO synthase (cNOs) was assumed to control hepatic sinusoidal micro-circulation. CNOS requires Ca^<++> ion during synthesis of NO and so has tight correlation with intra-cellular free Ca^<++> concentration. We established a new highly sensitive method for measurement of chemical compounds which is related to cNOS-dependent NO in whole blood at steady state, and are investigating the relationship among NO production, intra-cellular Ca^<++> mobilization and decrease of HBF by anesthetics.