Protecting the viability of hepatic allografts procured from non-heart-beating donors by blockade of endothelin and platelet activating factor in porcine liver transplantation

Problem: The function of hepatic allograft from non-heart-beating donors (N HBD) is significantly affected by warm ischemic injury before harvesting, Materials and Methods: The effects of the endothelin (ET) antagonist TAK-04 4 and the platelet activating factor (PAF) antagonist E5880 on the function of grafts from NHBD were evaluated in a porcine orthotopic liver transplan tation. The liver grafts were subjected to 90 min of warm ischemia and 4 ho urs cold preservation. Group 1 (n=4; n is the number of donor/recipient pai rs) was used as a control (untreated), In group 2 (n=4), donors and recipie nts were treated with TAK-044 (3 mg/kg), In group 3 (n=4), pigs were treate d with E5880 (0.3 mg/kg), In group 4 (n=4), pigs were treated with TAK-044 and E5880, Results: The 7 day survival rate of the recipients in groups 1, 2, 3 and 4 was 0, 25, 25 and 100%, respectively (p < 0.05, group 1 versus 4), The incr eases of the serum concentrations of aspartate transaminase, lactate dehydr ogenase and arterial lactate 1-4 hours after transplantation were significa ntly inhibited in the treated groups, Conclusion: The blockade of ET and PAF has protective effects on the functi on of hepatic grafts from NHBD.