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

Abstract

Background: 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.

Methods: 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.

Results: 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%.

Conclusions: This study established a new model of arterialized OLT in mice, which opens new avenues for research.