Synergistic effects of nafamostat mesilate rinse and Kupffer cell blockade for rat liver preservation

Transplant International : Official Journal of the European Society for Organ Transplantation
H OhdanK Dohi

Abstract

We investigated the efficacy of a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor) for liver preservation with modulation of Kupffer cell function. Orthotopic liver transplantation (OLT) was performed in male Lewis rats after 24 h of cold storage in University of Wisconsin organ preservation solution. After OLT, survival was determined, together with assays of blood chemistry, tissue NM metabolites, and histology 3 h after OLT. NM rinse was found to have a cytoprotective effect on liver parenchymal cells, based on enzyme data showing that NM rinse reduced the release of serum alanine aminotransferase significantly in comparison with saline rinse (P < 0.05). However, the effect was not sufficient to improve the survival rate. In contrast, when the donor was treated with gadolinium chloride 24-30 h before graft harvest, NM rinse improved the survival rate to around 80% compared with 25% for saline. The assay of NM metabolites in grafted liver tissue showed that pretreatment of the donor rats with GdCl3 delayed the degeneration of NM in the liver tissue. These data demonstrate that NM rinse and Kupffer cell blockade exert synergistic effects, leading to increased survival after cold-preserved li...Continue Reading

References

Sep 1, 1989·Transplantation·T S LieK Ogawa
Nov 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H ShimizuR E Falk
Oct 1, 1981·Pathology, Research and Practice·H KajiharaK Taguchi

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