• N Tomizawa, S Ohwada, T Ohya, Y Kawashima, I Takeyoshi, and Y Morishita.
• Second Department of Surgery, Gunma University School of Medicine, Gunma, Japan.
• J. Surg. Res. 1999 Feb 1; 81 (2): 230-7.

AbstractActivated neutrophils play an important role in reperfusion injury following hepatic ischemia. Neutrophil elastase is a powerful proteolytic enzyme. We investigated the possibility that ONO-5046. Na, which is a new recombinant-specific neutrophil elastase inhibitor, can reduce ischemia and reperfusion injury in the canine liver. Adult mongrel dogs (n = 19) were used in this experimental study. Seventy-five percent of the liver was resected after 60 min of vascular occlusion. The animals were divided into two groups. The ONO group (n = 8) was given ONO-5046. Na dissolved in saline starting 30 min prior to clamping the hepatic inflow and continuing for 4 h after reperfusion at a rate of 10 mg/kg/h. The nontreatment group (n = 11) received a saline solution for the same period. ALT and LDH levels were significantly lower (P < 0.05) in the ONO group than in the nontreatment group after reperfusion. Purine nucleoside phosphorylase and hyaluronic acid levels, which are markers of endothelial damage, were significantly lower (P < 0.05) in the ONO group than in the nontreatment group after reperfusion. Histologically, widely spread hepatocyte necrosis was found in dogs in the nontreatment group that died prematurely. Neutrophil infiltration of the sinusoids was less evident in the ONO group than in the nontreatment group. Neutrophil elastase inhibitor may prevent injuries of both endothelial and parenchymal cells in extended hepatectomy with vascular occlusion.Copyright 1999 Academic Press.

41 keywords...

hide…