FR128998 ameliorates liver injury in extended liver resection with ischemia in dogs

Background/Aims: Platelet-activating factor is one of the most potent phosp holipid mediators associated with inflammatory conditions such as ischemia and reperfusion injury, FR128998 (FR) is a novel platelet-activating factor receptor antagonist. In this study, we evaluated the effect of FR during a n extended liver resection with ischemia in a canine model. Methodology: Animals were divided into two groups: the control group (n=8), and the FR-treated group (n=7) in which FR was administered via the portal vein. While the right portal pedicle was clamped for 60min, the left porta l branch remained patent to avoid splanchnic congestion. Following reperfus ion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) was resected. Hepatic venous blood was collected to measure GPT, GOT, and LDH levels. Hepatic tissue blood flow wa s measured by a laser Doppler flow meter. The liver specimen was harvested for histological study. Results: GPT, GOT, and LDH levels after reperfusion were significantly (P<0 .05) lower in the FR-treated group than in the control group. Hepatic tissu e blood flow was maintained significantly (P<0.05) higher in the FR-treated group than in the control group. Histologically, accumulation of polymorph onuclear neutrophils significantly (P<0.05) decreased in the FR-treated gro up compared with the control group. The a-day survival rate was statistical ly (P<0.05) better in the FR-treated group than in the control group. Conclusions: FR128998 provides a protective effect for liver parenchyma and sinusoidal endothelial cells during extended Liver resection with ischemia .