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-heartbeating donors (NHBD) is significantly affected by warm ischemic injury before harvesting.
MATERIALS AND METHODS: The effects of the endothelin (ET) antagonist TAK-044 and the platelet activating factor (PAF) antagonist E5880 on the function of grafts from NHBD were evaluated in a porcine orthotopic liver transplantation. The liver grafts were subjected to 90 min of warm ischemia and 4 hours cold preservation. Group 1 (n = 4; n is the number of donor/recipient pairs) was used as a control (untreated). In group 2 (n = 4), donors and recipients were treated with TAK-044 (3 mg/kg). In group 3 (n = 4), pigs were treated 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 increases of the serum concentrations of aspartate transaminase, lactate dehydrogenase and arterial lactate 1-4 hours after transplantation were significantly inhibited in the treated groups.
CONCLUSION: The blockade of ET and PAF has protective effects on the function of hepatic grafts from NHBD.