Hyperammonemia induced by administration of glucose and insulin after hepatopancreatectomy in rats

Massive resection of both the liver and pancreas is performed as a radical procedure in some cases of advanced biliary cancer, but it has been reporte d that this disease is frequently complicated by hyperbilirubinemia or hepa tic insufficiency postoperatively, which is a serious hindrance to performi ng such extended surgery (Nimura et al., 1991; Nakamura ef al., 1992). To investigate the pathogenesis of hepatic dysfunction after hepatopancreat ectomy, we performed 4 surgical procedures consisting of 68% hepatectomy, 9 0% pancreatectomy, 68% hepatectomy plus 90% pancreatectomy (hepatopancreate ctomy) and sham-surgery in rats. Then, rats were continuously infused with 5% or 20% glucose solution at a constant speed (50 mL/day) for 24 hours in the fasting state, thus creating a total of 8 groups. During infusion of 20 % glucose solution into rats with pancreatectomy or hepatopancreatectomy, i nsulin (1 U/5 g glucose) was added to the solution to adjust the blood gluc ose. In rats infused with 20% glucose solution with added insulin after hep atopancreatectomy, the blood glucose level did not differ, but adenosine 5' -triphosphate (ATP) and energy charge levels in the liver tissue were signi ficantly lower, while the blood ammonia level was significantly higher than those in the other 7 groups. These results demonstrate that continuous inf usion of high concentrations of glucose solution with added insulin after h epatopancreatectomy in rats reduces hepatic mitochondrial function, resulti ng in hyperammonemia due to reduced urea synthesis.