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

麻醉对肝循环、氧代谢、细胞内Ca^<>动员及肝损伤影响的研究

基本信息

批准号：
07671683
负责人：
MATSUMOTO Nobuyuki
金额：
$ 0.32万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

1)本文观察了氟烷、异氟醚和七氟醚对低氧血症和肝切除犬肝血流量（HBF）、氧代谢（HOM）和能量负荷（HEC）的影响。异氟烷和七氟烷维持HBF、HOM和HEC的效果优于氟烷。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基于HOM失衡的肝损伤。2)在体外循环（CPB）期间，芬太尼麻醉的比格犬也进行了HBF和HOM的研究。在CPB期间增加芬太尼剂量至50 μ g/kg/h可降低HBF并抑制HOM，而10 μ g/kg/h芬太尼对HBF和HOM的影响最小，只要灌注率在CPB前主动脉血流量值的80%以内。体外循环期间大剂量芬太尼合并低氧血症可能会导致肝脏损伤。3)器官灌注通过血管周围平滑肌的收缩和舒张来调节。一般来说，这种调节受一氧化氮（NO）产生和形成的影响，在肝窦中也是如此。在肝脏中，由组成型NO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Ca^++，因此与细胞内游离Ca^++浓度密切相关。我们建立了一种新的高灵敏度的方法，用于测量稳态时全血中与cNOS依赖性NO相关的化合物，并正在研究NO产生、细胞内Ca^++动员和麻醉剂引起的HBF减少之间的关系。