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

我们观察了猪肝移植后一氧化氮（NO）的变化，以及门静脉内给予一氧化氮合酶抑制剂对肝移植后再灌注损伤的抑制作用。首先，作为移植的初步实验，在热缺血再灌注模型中检测NO的生成和一氧化氮合酶抑制剂的作用。试验选用体重18-23kg的母猪。热缺血肝缺血120 min后经静脉-静脉旁路（肠系膜上静脉至左颈外静脉）再灌注。肝移植手术按常规进行。选择n -硝基- l -精氨酸甲酯（L-NAME）作为组成型一氧化氮合酶抑制剂，氨基胍（AG）作为诱导型一氧化氮合酶抑制剂。两种药物在肝缺血前静脉注射浓度均为10mg/kg。在温缺血模型中，高剂量的L-NAME使血压升高，但80%的猪在缺血或再灌注后70min内死亡。另一方面，给药AG不影响血压或生存。AG给药组一氧化氮的产生明显低于未给药组。与未给药组相比，再灌注后肝组织血流量明显增加，AST有降低的趋势。在移植中，在门静脉再灌注前，静脉内给予AG。与未给药组相比，NO的产生有减少的趋势，AST明显降低。这些实验结果表明，L-NAME在肝缺血再灌注中具有一定的损伤作用，因为在热缺血模型中大多数猪死亡。门静脉内给药AG对热缺血模型有保护作用。门静脉内给药AG对猪热缺血再灌注和肝移植有保护作用。少

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