PROTECTIONAND EVALUATION OF LIVER GRAFTFUNCTIONS PROCURED FROM NON-HEART-BEATING DONORS

实验1用猪进行原位LTx。在供体中，KCl注射引起心脏骤停，肝脏进行90min的热血凝。处理组以10 mg/kg的剂量给药TAK-044，供体和受体均在术后12小时内死亡，而处理组存活时间均超过4天（p<0.01）。治疗组存活率的提高与血清GOT和LDH浓度的降低、肝脏能量电荷的恢复和门静脉压的抑制有关。接枝冲洗前冲洗过的保存液中GOT和LDH浓度与接枝效果密切相关，处理组明显降低。<实验2>在睡眠中，心脏骤停是通过停止呼吸机引起的。肝脏进行45分钟的热化学处理，然后使用UW溶液进行8小时的冷保存，TAK-044仅以10 mg/kg的剂量给予受体，治疗组的术后生存和移植物功能明显优于未治疗组。结论。本研究提示TAK-044可改善同种异体肝移植功能，提示其在NHBD临床LTx中的应用潜力。洗净保存液中GOT和LDH的浓度可能为LTx前评估同种异体肝移植活力提供准确的手段

Experiment 1> Orthotopic LTx usingpigs were performed. In the donors, cardiac arrest was induced by KCl injection and the liverwas subjected to 90 min of warm isehemia. Thereafter, the liverwas harvested and stored for 4 lx)urs usingcold Euio-Collins solution In the treated group, TAK-044 was administered to both donons and recipients at the dose of 10 mg/kg All the untreated recipient pigs died within 12 hr after operation, whereas all of the treated pigs surviwd more than 4 days (p<0.01). The improved survival seen in the treated group was associated with a reduction in the serum concentrations of GOT and LDH, a restoration of hepatic energy charge, and a suppression in the portal venous pressure. Concentrations of GOT and LDH in the washed out preservation solution at the time of graft rinsing immediately before RPF, were cIosely correlated with the graft outcome, and were significantly lowerin the treated group. <Experiment 2> In the domrs, cardiac arrest was induced by stopping the ventilator. The liver was subjected to 45 min of warm is chemia followed by 8 hr cold preservation using the UW solution TAK-044 was administered only to recipients at the dose of 10 mg/kg Postoperative survival as well as graft function were significantly better in treated group than in the untreated group. Conclusions. The present study suggests that TAK-044 can improve the hepatic allograft function, indicatinga potential for use in cIinical LTx from NHBD.The concentrations of GOT and LDH in the washed out preservation solution may provide an accurate means of evaluating liver allograft viability before LTx