The effect of FR167653 in a canine total hepatic vascular exclusion model

Though liver grafts from non-heart-beating donors are now attracting much attention, these grafts inevitably suffer from severe warm ischemia. The aim of this study was to evaluate the effect of TNF-alpha and IL-1 suppression on warm ischemia-reperfusion injury in a canine total hepatic vascular exclusion model.

Warm ischemia was induced by 1-h total hepatic vascular exclusion with active splenofemuro-juglar bypass. Animals were divided into two groups. FR167653 (1 mg/kg/hr) was administered via the portal vein from 30 min prior to ischemia until 2 h after reperfusion to the FR group (n = 7), and a vehicle was administered to the control group (n = 7). The serum alanine aminotransferase, aspartate amino-transferase, lactate dehydrogenase, and hyaluronic acid levels were measured. Hepatic tissue blood flow was also measured. Liver specimens were harvested for histological study, and polymorphonuclear neutrophils were counted.

Serum liver enzymes were significantly (p < 0.05) lower, and hepatic tissue blood flow was kept significantly (p < 0.05) better in the FR group than in the control. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p < 0.05) lower in the FR group than in the control group.

FR167653 provides protective effects on hepatic warm ischemic injury in a canine total hepatic vascular exclusion model.