PROLONGED HEPATIC WARM ISCHEMIA IN NON-HEART-BEATING DONORS - PROTECTIVE EFFECTS OF FK506 AND A PLATELET-ACTIVATING-FACTOR ANTAGONIST IN PORCINE LIVER-TRANSPLANTATION

Background. Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx). Methods. The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepati c allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia a nd a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untr eated control group. In group 2 (n = 4), donors were pretreated with F K506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treat ed with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880. Results. All of the recipients in group 1 died w ithin 12 hours. In groups 2 and 3, half of the recipients survived mor e than 12 hours. In group 3, all of the recipients survived more than 2 days (p < 0.01 compared with group I). The improved survival seen in group 4 was associated with a reduction in the serum concentrations o f glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge. Conclusions. The present study suggests that FX 506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.