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

Hepatogastroenterology. 2003 Jan-Feb;50(49):161-4.

Abstract

Background/aims: 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.

Methodology: 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.

Results: 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.

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Hemodynamics / drug effects
  • Hepatic Veno-Occlusive Disease / complications*
  • Hepatic Veno-Occlusive Disease / drug therapy*
  • Hepatic Veno-Occlusive Disease / pathology
  • Immunosuppressive Agents / therapeutic use*
  • Liver Circulation / drug effects
  • Liver Transplantation / adverse effects*
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / pathology
  • Severity of Illness Index
  • Time Factors

Substances

  • FR 167653
  • Immunosuppressive Agents
  • Pyrazoles
  • Pyridines