title: Synergistic effects of nafamostat mesilate rinse and Kupffer cell blockade for rat liver preservation.
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 liver transplantation.
authors.affiliation: Second Department of Surgery, Hiroshima University, School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohdan
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Urushihara
authors.forename: R
authors.initials: R
authors.lastname: Sumimoto
authors.forename: T
authors.initials: T
authors.lastname: Asahara
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Dohi
mesh_terms: D000818:Animals; D001550:Benzamidines; D005682:Gadolinium / Q000494:pharmacology; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000502:physiology; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation; D051381:Rats; D011917:Rats, Inbred Lew; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
chemical_list: D001550:Benzamidines; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D005682:Gadolinium; C038958:gadolinium chloride; C032855:nafamostat