Pharmacologic graft protection without donor pretreatment in liver transplantation from non-heart-beating donors

Background. Non-heart-beating donors (NHBDs) are considered potential sourc es of transplant organs in an effort to alleviate the problem of donor shor tage in clinical liver transplantation. We investigated the possibility of pharmacologic protection of hepatic allo-graft function from NHBDs without donor pretreatment. Methods. Orthotopic liver transplantation was performed using pigs. In dono rs, cardiac arrest was induced by stopping the respirator. Forty-five minut es after cessation of the respirator, the liver was flushed with cold lacta ted Ringer's solution including heparin and with the University of Wisconsi n (UW) solution, and then preserved for 8 hr at 4 degreesC in the UW soluti on. The pigs were divided into two groups: a control group and a treated gr oup. In the treated group, an endothelin antagonist TAR-044 was added to th e UW solutions (10 mg/L), and TAK-044 (10 mg/kg body weight) and a platelet activating factor antagonist E5880 (0.3 mg/kg body weight) were also admin istered to the recipients. Results. TAK-044 and E5880 treatment significantly increased the 7-day surv ival rate of the recipients (100% vs. 17%, P<0.05), In the treated group, p ortal venous pressure immediately after reperfusion of the graft was signif icantly lower than in the control group, and postoperative increase in seru m concentrations of glutamic oxaloacetic transaminase and total bilirubin w as attenuated. Moreover, the energy charge and adenosine triphosphate conce ntration of the liver were rapidly restored after reperfusion. Conclusions. Pharmacologic modulation with TAK-044 and E5880 avoiding donor pretreatment can improve the viability of hepatic allografts procured from NHBDs.