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

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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.