LAZAROID U-74389G FOR 48-HOUR CANINE LIVER PRESERVATION1,2

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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.