title: Lazaroid U-74389G for 48-hour canine liver preservation.
abstract: Lazaroids have been reported to attenuate preservation and reperfusion injury. In this study, we examined whether lazaroids can improve the outcome after 48-hr canine liver preservation and transplantation. Adult female beagle dogs were randomized into 4 dosage groups (5 animals each). Lazaroid U-74389G was intravenously administered at a dose of 0 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg to donors 30 min before harvesting and also to recipients 30 min before revascularization. Control animals (0 mg/kg) were given the lazaroid vehicle. The liver grafts were orthotopically transplanted after 48 hr of hypothermic preservation in UW solution. Lazaroid treatment significantly improved outcome after transplantation. Five-day animal survival increased from 0% in the control to 60% in the 6 mg/kg group, 100% in the 10 mg/kg group, and 80% in the 15 mg/kg group. Lazaroid protected the hepatocytes from damage during preservation, and enhanced energy charge and hepatic blood flow after reperfusion. Histological alterations were significantly less severe in the lazaroid-treated groups. The area of necrotic hepatocytes decreased from 43.7 +/- 17.7 in the control to 13.5 +/- 3.0 in the lazaroid 10 mg/kg group. These results indicate that lazaroid U-74389G has potential for improvement of clinical liver preservation.
authors.affiliation: Pittsburgh Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
authors.forename: S
authors.initials: S
authors.lastname: Todo
authors.forename: N
authors.initials: N
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: V
authors.initials: V
authors.lastname: Subbotin
authors.forename: A
authors.initials: A
authors.lastname: Nemoto
authors.forename: I
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: T E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D016031:Liver Transplantation; D009926:Organ Preservation; D011281:Pregnatrienes / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D011281:Pregnatrienes; C074965:U 74389F