The new strategy of liver transplantation from marginal donors using serine protease inhibitor

Transplant Proc. 2009 Jan-Feb;41(1):36-9. doi: 10.1016/j.transproceed.2008.09.066.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamidines
  • Brain Death
  • Graft Survival / drug effects
  • Guanidines / pharmacology
  • Guanidines / therapeutic use
  • Liver / ultrastructure
  • Liver Transplantation / pathology*
  • Male
  • Organ Preservation / methods
  • Rats
  • Rats, Wistar
  • Serine Proteinase Inhibitors / pharmacology*
  • Serine Proteinase Inhibitors / therapeutic use
  • Survival Rate
  • Tissue Donors / statistics & numerical data*

Substances

  • Benzamidines
  • Guanidines
  • Serine Proteinase Inhibitors
  • nafamostat