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

无心跳供体肝移植的保护和评估

• 批准号: 09671207
• 负责人: TAKADA Yasutsugu
• 金额: $ 1.98万
• 依托单位: TSUKUBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671207/
• 关键词: LIVER TRANSPLANTATION; PIG; NON-HEART-BEATING DONOR; ENDOTHELIN; TAK-044; GRAFTVIABILITY; MICROCIRCULATION; グラフト バイアビリティー; 肝虚血障害; 血小板活性化因子

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

实验一、猪原位肝移植。供体采用KCl诱导心脏停搏，肝脏热缺血90 min。此后，收获肝脏并使用冷的Euio-Collins溶液储存4小时。在给药组中，以10 mg/kg的剂量向供体和受体给予TAK-044。所有未给药的受体猪均在术后12小时内死亡，而所有给药的猪均存活4天以上（p<0.01）。在治疗组中观察到的生存率改善与血清GOT和LDH浓度降低、肝脏能量负荷恢复和门静脉压抑制相关。在RPF前即刻冲洗移植物时，冲洗出的保存液中GOT和LDH的浓度与移植物的结果密切相关，并且在治疗组中明显较低。<Experiment 2>在domrs中，通过停止呼吸机诱导心脏骤停。肝脏经过45分钟的温缺血，然后使用UW溶液冷保存8小时，仅对受体给予10 mg/kg剂量的TAK-044。治疗组的术后生存率和移植物功能明显优于未治疗组。结论.本研究提示TAK-044可改善移植肝的功能，提示其在临床肝移植中的应用潜力。在肝移植前，检测洗脱液中GOT和LDH的浓度可作为评价移植肝存活的一种准确方法

项目成果

Fukunaga K,et al.: "Successful liver trnsplantation from non-heart-beating donors by blackade of endothelin and PAF." Transplant Proc.30. 3797 (1998)

Fukunaga K 等人：“通过黑化内皮素和 PAF，从无心跳的供体中成功进行肝移植。”

Takada Y,Taniguchi H,Fukunaga K,Yuzawa K,Otsuka M,Todoroki T,Iijima T,Fukao K: "Hepatic allograft procurement from non-heart beating donors : Limits of warm is chemia in porcine livertransplantation." Transplantation. 63. 369-373 (1997)

Takada Y、Taniguchi H、Fukunaga K、Yuzawa K、Otsuka M、Todoroki T、Iijima T、Fukao K：“从非心跳供体获取同种异体肝：温暖的限制是猪肝移植中的化学反应。”

高田泰次. 他: "肝虚血再潅流障害" 移植. 33. 59-72 (1998)

Taiji Takada 等：“肝缺血再灌注损伤” 移植 33. 59-72 (1998)。

Takada Y,Taniguchi H,Fukunaga K,Yuzawa K,Otsuka M,Todoroki T,Iijima T,Fukao K.: "Prolonged hepatic warm is chemia in non-heart-beating donors : Protective effects of FK506 and a platelet activating factor antagonist in porcine livertransplantation" Surger

Takada Y、Taniguchi H、Fukunaga K、Yuzawa K、Otsuka M、Todoroki T、Iijima T、Fukao K.：“长期肝温是无心跳供体中的化学反应：FK506 和血小板活化因子拮抗剂对患者的保护作用

Takada Y,et al.: "Prolonged hepatic warm ischemia in non-heart-beating donors. Protective effects of FK506 and a platelet activating factor antagonist in porcine liver transplantation." Surgery. 123. 692-698 (1998)

Takada Y 等人：“无心跳供体的长期肝脏热缺血。FK506 和血小板活化因子拮抗剂在猪肝移植中的保护作用。”