Beneficial-effects of Platelet-activating-factor Receptor Antagonist Web-2170 On 90-minute Hepatic Inflow Interruption

Objective: To study the effects of different doses of platelet activating factor receptor antagonist WEB 2170 on animal survival, haemodynamics, reperfusion and ultrastructural changes in the ischaemic liver in rats undergoing 90-min total hepatic inflow interruption (THII). Design: Sixty-five rats were divided into five groups. All animals underwent 90-min THII. Group 1 served as controls. Group 2 underwent THII alone. Group 3 received an intravenous injection of 1 mg/kg WEB 2170 prior to THII. Group 4 received a bolus injection of 3 mg/kg WEB 2170 before THII. Group 4 received a bolus injection of 3 mg/kg WEB 2170 before THII. Group 5 received 3 mg/kg WEB 2170 before, during and after THII. The liver reperfusion index using laser Doppler flowmetry, the time of ischaemic liver initiative reperfusion, and scanning electron microscopy were performed to evaluate the results of different dose schedules. Setting: Lund University Hospital, Lund, Sweden. Results: Animal survival rate, liver reperfusion index, the time of ischaemic liver initiative reperfusion and ultrastructural damage of the ischaemic liver were markedly improved in the groups treated with WEB 2170 compared with the non-treated 90-min THII group. The best result was obtained in the group receiving the three separate doses. Conclusion: In the 90-min THII model, WEB 2170 protects the liver from ischaemia-reperfusion injury and the spread of damage to the post-stasis splanchnic organs. These beneficial effects may be extended to hepatic transplantation or major resections of the liver.