The effects of intraportal administration of nitric oxide synthase inhibitor for attenuation of reperfusion injury in pig liver transplantation.

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We examined the change in nitric oxide (NO), and the effects of intraportal adiministration of nitric oxide synthase inhibitor for attenuation of reperfusion injury in liver transplanation in pig. First, the evaluation of production of NO and effect of nitric oxide synthase inhibitor were examined in warm ischemic reperfusion model as a preliminary experiment of transplantation. Female pigs weighing 18-23kg were used in these experiments. Warm ischemic liver was subjected to 120 min of total hepatic ischemia followed by reperfusion under veno-veno bypass (superior mesentric vein to left external jugular vein). Liver transplantation was performed in the usual manner. N-nitro-L-arginine methyl ester (L-NAME) was chosen as the inhibitor of constitutive nitric oxide synthase, and aminoguanidine (AG) was chosen as the inhibitor of inducible nitric oxide synthase. The concentration of both drugs, administered intraportally before hepatic ischemia, was 10mg/kg. In warm ischemic model, adminis … More tration of L-NAME increased blood pressure, but 80% of the pigs died during ischemia or within 70min after reperfusion. On the other hand, administration of AG did not affect blood pressure or survival. The production of NO was significantly lower in the AG administration group compared with the non-administered group. Hepatic tissue blood flow after reperfusion was significantly increased, and AST trended to decrease compared with the non-administered group. In transplantation, AG was administered intraportally before reperfusion of portal vein. The production of NO showed a tendency to decrease, and AST was significantly decreased compared with the non-administered group. The results of these experiments showed that L-NAME was injurious in hepatic ischemia and reperfusion, because the majority of pigs died in the warm ischemic model. Intraportal administration of AG had protective effects in warm ischemic model. Intraportal administration of AG had protective effects in warm ischemic reperfusion and in liver transplantation in pig. Less