Lazaroid U-74389G for 48-hour canine liver preservation

Transplantation
S TodoT E Starzl

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 lazar...Continue Reading

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Citations

Jul 2, 2019·Experimental and Therapeutic Medicine·Maria I KorontziApostolos Papalois
Dec 22, 1999·Journal of Cardiovascular Pharmacology·P L NgoL Dumont
Jun 29, 2000·Scandinavian Cardiovascular Journal : SCJ·K KuwakiT Abe
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Dec 5, 1998·Transplantation Proceedings·T TakahashiY Morishita

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