Experimental study on platelet activating factor and systemic circulatory failure caused by ischemic liver

Ischemic hepatic failure is often accompanied by systemic circulatory failure. In hepatic graft failure, this circulatory derangement is reported to be cured by retransplantation. This suggests that ischemic liver might release some substance which causes circulatory depression. In the present study, the role of platelet activating factor (PAF) in systemic circulatory failure after liver ischemia was investigated. Partial hepatic ischemia was induced in ten dogs by clamping the afferent vessels to almost 70% of the liver for 60 minutes, and non-ischemic lobes were resected after declamping. Five were pretreated with 3 mg/kg of PAF antagonist (CV6209) i.v. (PAF antagonist group), and the others were pretreated with saline (control group). The mean arterial pressure markedly decreased after declamping in control group (89 +/- 25mmHg 25 min after declamping), but it did not fall in PAF antagonist group (155 +/- 221mmHg). Three died from either shock or hepatic failure within a week in control group, but none died in PAF antagonist group. In conclusion, ischemic liver was suggested to release PAF and depress systemic circulation. And a PAF antagonist was expected to be an effective drug for the circulatory derangement caused by ischemic liver.