Effect of Nitric Oxide on ex vivo normothermic liver perfusion with purely artificial products using artiicial blood.

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Background. We tried to development of ex vivo hepatic organ culture system, and we have previously demonstrated that development of a normothermic perfusion system that employed artificial products. In this study, we investigated the effects of administration of iNOS inhibitor or NO donor in a normothermic perfusion system with an artificial perfusate using artificial blood.Materials and Methods. A liver graft from a female pig weighting 15 kg was harvested in the usual manner. The Perfusion solution consisted of artificial blood (Neo Red Cell), L-15 medium, distilled water, bovine serum albumin, NaHCO3, NaOH, KC1, human regular insulin, 50% glucose solution, and Hexamethasone. The isolated liver was perfused with this oxygenated perfusate through the portal vein at a rate of 300 ml/min for 6 hours. Selective iNOS inhibitor or NO donor was administration in this perfusion system.Results., Serum contents of AST and LDH level in iNOS inhibitor treatment group markedly dropped and improve oxygen consumption level compared with control group. Histological findings showed that few necrotic areas in 3 hour after perfusion in iNOS inhibitor treatment group compared with control group. NO donor administaration in the perfusion solution improved FischerAfs ratio and decrease cytotoxic amino acid such as serine and methionine. Conclusions. A selective iNOS inhibitor inhibited isolated liver injury. NO donor administration contributed to improvement of amino acid metabolism.