Platelet-activating factor antagonism enhances the liver's recovery from warm ischemia in situ

Hepatic outcome after ischemia is compromised by anoxic injury and by release of oxygen free radicals or other pathological mediators at reperfusion. The platelet-activating factor (PAF) is an endogenous lipid-mediator which plays a key role in catalysing various pro-inflammatory processes. In this study the possible influence of platelet-activating factor antagonism was investigated on the integrity of the vascular endothelium, on free radical-mediated peroxidation and on post-ischemic functional outcome of the liver in the rat. Animals under pentobarbital anesthesia were subjected to 60 min of ischemia of the left and median liver lobes followed by 30 min of reperfusion in vivo. Pre-ischemic injection of the platelet-activating factor antagonist BN 52021 resulted in a significant reduction of endothelial enzyme loss into the plasma (purine nucleoside phosphorylase 56.2 vs. 83.1 U/l), and lowered hepatic lipid peroxidation (malondialdehyde 830 vs 932 nmol/g), leading to a significant improvement of postischemic bile flow and higher tissue levels of ATP. This suggests that the platelet-activating factor may play an important role in hepatic ischemia-reperfusion injury and that PAF antagonists like BN 52021 may be useful for clinical treatment.