Comparison of arterialized and nonarterialized orthotopic liver transplantation in mice: prowess or relevant model?1

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Abstract
New insights into mechanisms of injury in orthotopic liver transplantation (OLT) often come from experiments in small animal models. Mice are particularly suitable because of the growing availability of gene-altered animals and specific antibodies. A validated model of OLT in mice is not available and, in particular, the role of rearterialization is unknown. Therefore, we developed a new model of OLT in mice, and we compared liver injury and animal survival in the presence and the absence of arterial blood supply. Syngenic OLT was performed in male Balb/c mice. An arterial segment was removed en bloc with the graft in the donor animal and subsequently implanted in a recipient animal using a combination of suture and cuff technique. In some animals, rearterialization was performed with an end-to-side anastomosis between the recipient aorta and the graft artery using a running suture. Rewarming ischemia time was consistently kept below 20 min. All animals (8/8) survived permanently in the presence of a rearterialized graft, whereas only 50% (4/8) were alive at 2 weeks in the absence of arterial supply ( P=0.025). Serum aspartate aminotransferase levels were significantly lower in the presence of arterial supply at 1 and 3 days and 2 weeks after OLT. Serum levels of alkaline phosphatase normalized within 2 weeks in animals with arterialized grafts, whereas levels remained high (3x normal values) in nonarterialized animals. Histologic examination supported a primary injury to the small bile ducts. Viability of arterialized grafts preserved for 16 hr in cold University of Wisconsin solution was 100%. This study established a new model of arterialized OLT in mice, which opens new avenues for research.