Orthotopic liver transplantation from cardiac death donors in the mouse: a new model and evaluation of cardiac death time

Objective(s): The goal of this research was to develop a mouse orthotopic liver transplantation (LTx) model from donor-after-cardiac-death (DCD) grafts. Materials and Methods: Mice were randomly assigned to the experimental group or the sham group. The mice in the experimental group were divided into three groups according to the warm ischemia time (WIT) of liver graft: normal LTx, WIT ۳۰ minute (min) +LTx and WIT ۴۵ min +LTx. The descending aorta was clamped using a miniature aortic clamp to simulate cardiac arrest in the DCD grafts. Subsequently, the grafts were orthotopically transplanted into C۵۷BL/۶ mice. The ۷-day survival rate, serum alanine aminotransferase (ALT), inducible nitric oxide synthase (iNOS), interleukin-۶ (IL-۶) mRNA level, tumor necrosis factor-alpha (TNF-α) mRNA level, as well as hepatic pathologic alterations were observed. Results: The ۷-day survival rate was markedly lower in the WIT ۴۵ min+LTx group than that in the normal LTx group (۲۵% versus ۱۰۰%, P-value<۰.۰۵), with no significant difference between the WIT ۳۰ min +LTx and normal LTx group (۷۵% versus ۱۰۰%, P-value>۰.۰۵). Serum ALT level of WIT ۴۵ min+LTx group was markedly higher than that of normal LTx and WIT ۳۰ min+LTx group (P-value<۰.۰۱). There were significant differences in necrosis and apoptosis among the three groups (P-value<۰.۰۵). The expression of iNOS, IL-۶ mRNA and TNF-α mRNA in WIT ۴۵ min +LTx group all increased significantly compared with the normal LTx and WIT ۳۰ min+LTx group. Conclusion: The DCD LTx model is feasible in the mouse and would provide many advantages for biomedical research on LTx from DCD grafts.

Keywords:

Animal model , Liver transplantation , Primary graft dysfunction , Reperfusion injury , Warm ischemia time