The New Strategy of Liver Transplantation From Marginal Donors Using Serine Protease Inhibitor

Abstract Objectives The purpose of this study was to establish a safe technique to procure liver grafts from marginal donors such as non–heart-beating donors (NHBD). Materials and Methods Male Wistar rats were divided into five groups: (1) heart-beating (HB) group, livers were retrieved from HB donors; (2) non-HB (NHB) group, livers were retrieved from uncontrolled NHBD that had experienced the apnea-induced agonal condition; (3) nafamostat mesilate (NM) group, livers retrieved in the same manner as NHBD but pretreated with NM (0.2 mg/kg/h for 30 minutes); (4) prostaglandin I2 (PG) group, livers retrieved in the same manner as NHBD but pretreated with the (33 ng/kg/h, for 30 minutes); (5) NM + PG group, livers retrieved the same manner as NHBD but pretreated with NM and PG. After 1-hour cold preservation, the organs were transplanted according to Kamada's method. We examined aspartate transferase (AST) alanine transferase (ALT), lactate dehydrogenase, interleukin-1 beta, tumor necrosis factor-alpha, and thromboxane B2 (TXB2) at 24 hours after transplantation. We also performed histological examinations using electron microscopy. Results The number of survivors at 7 days after liver transplantation among the groups were 9/9, 0/9, 1/9, 1/9, and 3/9. The values of AST, ALT, and lactate dehydrogenase at 24 hours after transplantation in the NM + PG groups were slightly lower than those in the NHB group, but there were no significant differences among those groups. On the histological examination, the NM + PG group showed well–preserved sinusoidal endothelial cells. Conclusion The strong serine protease inhibitor, NM, and PG may support sinusoidal endothelial cells, a promising strategy for liver transplantation from marginal donors.