We investigated whether the stable prostacyclin analogue (OP-2507; OP) would ameliorate warm ischemia-related injury of the liver graft under conditions of a nonbeating heart. Thirty-six mongrel pigs were arranged into 3 groups of 6 pairs. Group 1 pigs underwent orthotopic liver transplantation from heart-beating donors (HBD). In group 2, animals received liver grafts from nonheart-beating donors (NHBD), defined as 30 min of cardiac arrest. Group 3 pigs received grafts from NHBD, but the donor had been pretreated with OP by intraportal infusion (2 microg/kg x min for 30 min immediately before the induction of cardiac arrest). The grafts were preserved at 4 degrees C in Euro-Collins solution in which OP was dissolved at 200 microg/l. Five-day survival rates after transplantation improved significantly in OP-treated animals (3/6, for group 3), compared with 0/6 for group 2 (P < 0.05, generalized Wilcoxon test). Five of 6 animals survived more than 5 days in the HBD group (group 1). Although the serum transaminase activities and bile production did not differ in the early phase of recirculation among the groups, there was a significant improvement in the hepatic microcirculatory environment in the surviving groups (groups 1 and 3). Analysis of arterial prostanoid levels showed a substantial suppression of PGE2 release by OP treatment following reperfusion. Our data indicate that a stable prostacyclin analogue can be clinically useful for expanding the donor pool by improving the quality of the liver graft.