NEW LIVER SUPPORT SYSTEM USING EXVIVO PERFUSED LIVER

使用 EXVIVO 灌注肝脏的新型肝脏支持系统

• 批准号: 09671344
• 负责人: KAMIYAMA Yasuo
• 金额: $ 1.22万
• 依托单位: KANSAI MEDICAL 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 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671344/
• 关键词: liver failure; hepatic coma; liver support; liver perfusion; xenoperfusion; liver preservation; liver failure; hepatic coma; liver support; NO; HGF; liver perfusion; liver fuilure

This study was conducted to simplify our liver support system used in patients with hepatic coma (Artificial Organ 6(4) : 433-446,1982). To prolong preservation time of the isolated liver, we tried to preserve the liver at a temperature just above the freezing point. In addition, the mechanism was studied by which NO affects the energy metabolism of the failed liver.1. The recipient pigs underwent a ligation of the portal vein and hepatic artery following portacaval shunt. An isolated liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 hours using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support of the liver failure pig was well maintained. The oxygen consumption and bile production were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure. These findings suggest that this liver support system has sufficient capacity to support a failed liver.2. We have confirmed the specific freezing point of rat liver and preserve it at a temperature just above that point (-0.8 C). Adenine nucleotide metabolism of the liver preserved at this temperature was well maintained as compared with the organ preserved at 4 C. It is suggested that this novel preservation technique prolong the preservation period.3. In septic patients with liver failure, NO levels in sera were increased and arterial blood ketone body ratio reflecting liver mitochondrial redox state, was depressed. There was a reciprocal relationship between NO level and the ratio. However, in the pig with ischemic liver NO was not increased.

进行这项研究是为了简化我们用于肝昏迷患者的肝脏支持系统（Artificial Organ 6（4）：433- 446，1982）。为了延长离体肝脏的保存时间，我们试图将肝脏保存在略高于冰点的温度下。此外，还探讨了NO影响肝衰竭能量代谢的机制.受体猪在门腔静脉分流后进行门静脉和肝动脉结扎。用来自受体猪的动脉血灌注离体肝脏，同时监测离体灌注肝脏的代谢能力。用缺血性肝衰竭猪的动脉血灌注离体肝脏超过24小时是可能的。在肝衰竭猪的支持过程中，离体肝脏的活力保持良好。与肝衰竭猪相连的离体肝脏的耗氧量和胆汁产量显著高于与无肝衰竭猪相连的器官。这些研究结果表明，这种肝脏支持系统有足够的能力来支持失败的肝脏。2.我们已经确定了大鼠肝脏的特定冰点，并将其保存在略高于该点的温度（-0.8 ℃）。与4 ℃保存的器官相比，在此温度下保存的肝脏的腺嘌呤核苷酸代谢保持良好。表明这种新的保鲜技术可以延长保鲜期.脓毒症合并肝功能衰竭患者血清NO水平升高，反映肝线粒体氧化还原状态的动脉血酮体比值降低。NO水平与比值呈负相关。然而，在猪缺血肝NO没有增加。

项目成果

Yoshida K, Matsui Y, Tu Wei, Kaibori M, Kwon A-H, Yamane A, Kamiyama Y: "A Novel Conception for Liver preservation at a Temperature Just Above Freezing Point."Journal of Surgical Research. 81. 216-223 (1999)

Yoshida K、Matsui Y、Tu Wei、Kaibori M、Kwon A-H、Yamane A、Kamiyama Y：“在冰点以上温度保存肝脏的新概念。”外科研究杂志。

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K.Yoshida: "A Novel Conception for Liver Preservation at a Temperature Just Above Freezing Point" Journal of Surgical Research. 81. 216-223 (1999)

K.Yoshida：“在冰点以上温度下保存肝脏的新概念”外科研究杂志。