Under conventional hypothermic preservation conditions, however, the biological Protein Tyrosine Kinase inhibitor activities of liver grafts are suppressed to unmeasurable levels and the uptake of therapeutic substances is inhibited. To overcome these limitations, we established a new mouse model of liver transplantation including a machine graft perfusion process and achieved an extracorporeal non-hypothermic
period for evaluation and improvement of the graft viability in this study. We developed a new organ perfusion machine in which an oxygenated perfusion of the liver graft can be performed at a wide range of temperatures. The liver graft was harvested with the diaphragm, and the intra-thoracic IVC was clamped to form a closed perfusion pathway. We
adopted William medium E as the perfusate, and oxygenated it with 100% oxygen. After harvesting, a liver graft was connected to the perfu-sion circuit and a graft perfusion was initiated at 4 degrees C. Thereafter the temperature was raised to 25 degrees C and a sub-normothermic graft perfusion was performed for 60 min. The perfusion speed was at this website 2.5ml/min. After the sub-normo-thermic perfusion, the temperature was lowered again, and the graft was detached and prepared at 4 degrees C. Liver transplantation was performed according to Qian’s method. In this model (n=4), the mean oxygen consumption indicated by the difference of the oxygen partial pressure between the inflow and the outflow perfusate was 74.7 mmHg and the mean carbon dioxide production indicated by the carbon dioxide
partial pressure in the outflow perfusate was 0.0 mmHg at 4 degrees C. During sub-normothermic perfusion at 25 degrees C, the mean oxygen consumption and the mean carbon dioxide production were increased to 290.8 mmHg and 5.6 mmHg respectively. All recipient mice that had undergone liver transplantation selleckchem using liver grafts after sub-normothermic machine perfusion at 25 degrees C for 60 min survived more than 7 days (n=4). In conclusion, we confirmed that metabolic activities of liver grafts were kept at substantial levels and evaluable during sub-normothermic machine perfusion, and succeeded in liver transplantation after sub-normothermic machine perfusion preservation. Disclosures: The following people have nothing to disclose: Masato Fujiyoshi, Akinobu Take-tomi Background: We showed previously that preparative hepatic X-irradiation (HIR) before hepatocyte transplantation (HT), followed by mitotic stimulation with triiodothyronine (T3) permits hepatic repopulation. Aim: To circumvent the cardiac side effects of T3, we sought a substitute for repopulating the liver of apolipoprotein-deficient (ApoE-/-) hypercholesterol-emic mice. We tested the hypothesis that transplanting wild-type hepatocytes in HIR-pretreated ApoE-/- mice, followed by administration of GC-1 (a thyroid hormone receptor-b (TR-b) selective agonist), should ameliorate hypercholesterolemia.