LAZAROID U-74389G FOR 48-HOUR CANINE LIVER PRESERVATION

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. Adu lt 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 harves ting and also to recipients 30 min before revascularization. Control a nimals (0 mg/kg) were given the lazaroid vehicle, The liver grafts wer e orthotopically transplanted after 48 hr of hypothermic preservation in UW solution, Lazaroid treatment significantly improved outcome afte r transplantation. Five-day animal survival increased from 0% in the c ontrol 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 damag e during preservation, and enhanced energy charge and hepatic blood fl ow after reperfusion, Histological alterations were significantly less severe in the lazaroid-treated groups. The area of necrotic hepatocyt es decreased from 43.7+/-17.7 in the control to 13.5+/-3.0 in the laza roid 10 mg/kg group. These results indicate that lazaroid U-74389G has potential for improvement of clinical liver preservation.