Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintain ing organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise , the harmful effects of enhanced nitric oxide production induced by induci ble nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has be en characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with isch emia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ische mia by partial inflow occlusion. After reperfusion the nonischemic lobes we re resected and the remnant liver function was evaluated. The dogs were div ided into two groups: the control group (n = 7) and the FK409 group (n = 6) , which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and ser um endothelin-1 level after reperfusion were significantly better in the FK 409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia. (J Am Coll Surg 2001;193:264-271. (C) 2001 by the American College of Surgeons).