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

本实验观察了猪肝移植再灌注损伤时一氧化氮（NO）的变化，以及门静脉注射一氧化氮合酶抑制剂对减轻再灌注损伤的作用。首先，作为移植的初步实验，在热缺血再灌注模型中检测NO的产生和一氧化氮合酶抑制剂的作用。在这些实验中使用体重18- 23 kg的雌性猪。使热缺血肝脏经受120分钟的全肝缺血，随后在静脉-静脉旁路（上级肠系膜静脉至左颈外静脉）下再灌注。以常规方式进行肝移植。选择N-硝基-L-精氨酸甲酯（L-NAME）作为组成型一氧化氮合酶的抑制剂，选择氨基胍（AG）作为诱导型一氧化氮合酶的抑制剂。肝缺血前门静脉给药的两种药物浓度均为10 mg/kg。在热缺血模型中， ...更多信息 L-NAME可使血压升高，但80%的猪在缺血或再灌注后70 min内死亡。另一方面，AG的施用不影响血压或存活率。与未给药组相比，AG给药组中NO的产生显著降低。与未给药组相比，再灌注后肝组织血流量显著增加，AST呈下降趋势。移植时，门静脉再灌注前门静脉注射AG。与未给药组相比，NO的产生呈下降趋势，AST显著降低。实验结果表明，L-NAME对肝脏缺血再灌注损伤较大，在热缺血模型中，大部分猪死亡。门静脉注射AG对热缺血模型有保护作用。门静脉注射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