Developmental Research on Preservation of Liver Graft by Improving the Hepatic Microcirculation

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In this project, we investigated (1)the role of hepatic microcirculation on the re-perfusion injury and (2)the preservation condition for the graft in liver transplantation.The mechanisms to control sinusoidal blood flow were investigated using cultured Ito cells and Kupffer cells which exist in sinusoid. Immunohistochemical staining revealed that contractile proteins such as actin, myosin and desmin were richly distributed in Ito cells. Addition of vasoactive substance, endothelin-1, caused the contraction of Ito cells and this contractile activity was thought to contribute on sinusoidal contraction and control of blood flow. Kupffer cells showed active phagocytic activity with the actomyosin system and Kupffer cells with ingested foreign substances might block the sinusoidal blood flow. The predictive factors for the re-perfusion injury was investigated and revealed that the oxygenation of the surface of the liver was a best available for prediction of the prognosis of liver transplantation.Although, the UW solution is standard for the liver preservation, we developed a new solution called "Carolina Rinse solution" for the better preservation. The clinical trial to assess the benefit of this solution for the liver transplantation has begun in Mayo Clinic in USA.