Elucidation of Mechanism in primary graft nonfunction of transplanted fatty liver graft and detection of methods preventing the mechanism

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1. Making an animal modelAs a rat model with a moderately (30〜60%) fatty liver, we could make it nearly equal to human fatty liver by feeding the rat with cholesterol-rich meal.2. Examination of mitochondrial ATP synthesisCompared fatty liver model (F-model) to normal model (N-model) about liver tissue ATP, energy charge, and the activity of proton ATPase, there were no significant differences among them.3. Examination of injury of sinusoidal lining cells (SLCs)To clarify injury of SLCs, we measured hyaluronic acid (HA) of blood and compared it in F-model to it in N-model. HA in F-model was significantly higher than in N-model, so it was suggested that SLCs of F-model was more fragile than those of N-model.4. Results of liver transplantationWhole fatty liver was resected and was stored in cold UW solution for 1, 6, 12 hours. After storage, we transplanted the graft orthotopically and compared survival rate of rat with fatty liver graft to that with normal liver graft. While all of the recipients with normal liver grafts survived for more than one week, survival rate at one week of recipients with fatty liver grafts stored in 6 hours was 40% and that in 12 hours was 0%. Mitochondrial ability of ATP synthesis after 6 hour-storage was not significantly different between fatty and normal liver graft, but after repurfusion the injury of SLCs of fatty liver graft was severer than that of normal graft.5. Preparation of drugs for preventing reperfusion injury(1) To eliminate Kuppfer cells which strongly affected repurfusion injury, L-DMDP was pretreated in donors, and (2) to inhibit PLAィイD22ィエD2 activity at repurfusion, liver graft was rinsed with Nafamostat mesilate (NM) rinse solution. However, the rats with fatty liver grafts were not improved to survive by preparation of either drug.