Conditioning of liver grafts by donor bolus pretreatment with epoprostenol - In vivo microscopy analysis of impact on ischemia/reperfusion injury in rat liver transplants

Despite improved preservation methods, graft dysfunction after liver transplantation continues to contribute considerably to postoperative morbidity and mortality, In clinical and experimental studies prostaglandin (PG)I-2 analogs proved effective in the treatment of liver damage of different origin. Using in vivo fluorescence microscopy in a rat liver transplantation model, we studied the effect of donor bolus pretreatment with the PGI(2) analog epoprostenol on hepatic graft revascularization. After epoprostenol bolus pretreatment (group 1: liver transplantation/PGI(2)), perfusion of liver sinusoids after reperfusion was significantly improved as compared with untreated donor livers (group 2: liver transplantation (95.2+/-0.6% vs. 75.3+/-3.8%, mean +/- SEM; P=0.001) and epoprostenol was found almost in the range of that in normal nontransplanted livers (99.4+/-0.2%). In addition, leukocyte adherence in liver lobules (21.0+/-3.5 vs, 115+/-11.5 n/lobule; P=0.001) and postsinusoidal venules (23.0+/-8.8 vs, 113+/-11.3 n/mm(2) endothelial surface; P=0.002) was significantly reduced in the pretreated grafts. Bile production in the recipient was significantly increased by epoprostenol pretreatment of the donor (1.88+/-0.4 0.63+/-0.13 g/100 g liver*1 hr; P=0.015), indicating restored liver function, These results suggest that the prostacyclin analog epoprostenol is effective in preconditioning the graft prior to transplantation, i.e., improving preservation and increasing graft resistance to ischemia/reperfusion injury. Thus, favorable effects on early graft function after clinical liver transplantation may be achieved by introducing epoprostenol pretreatment into the harvesting procedure.