肝臓外科と一酸化窒素（NO） : 誘導型NO合成酵素阻害剤による虚血再灌流障害抑制効果

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  • Liver Surgery and Nitric Oxide : Inhibition of Ischemia Reperfusion Injury by iNOS Inhibitor

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Hepatic ischemia reperfusion （I/R） injury is common incident in the liver surgery and liver transplantation. Recently, nitric oxide （NO） has received much attention as a substance related to I/R injury, especially NO from inducible NO synthase （iNOS） which convert to peroxynitrite by reaction with superoxides. We have been examined relationship between NO and hepatic I/R injury using an hepatic warm I/R model in the pig. In this model, we investigated hepatic NO production using a microdialysis method. After reperfusion, iNOS expression appeared in Kupffer cells and neutrophils, and the following findings were recognized; increase of NO production, the formation of thrombocyte thrombi, the expression of peroxynitrite, and apoptosis and necrosis. The frequency of apoptotic cells was very low levels compared with necrotic cells. An iNOS inhibitor significantly attenuated these findings. In the liver transplantation and hepatectomy models, the same results could be obtained. From these observation, the express ion of iNOS was the major cause of I/R injury, and the iNOS inhibitor greatly attenuated I/R injury. As a extended study, we tried to develop the new strategies of evaluation of graft of non-heart-beating donors using hepatic microdialysate hypoxanthine levels, and prediction of the viability of the graft was possible. Next, We tried to make an ex vivo functioning liver system using artificial blood in the pig liver, and succeeded 5 hours perfusion with this system.

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