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EXPERIMENTAL STUDIES ON AUXILIARY LIVER TRANSPLANTATION BASED ON REDOX THEORY

基于氧化还原理论的辅助肝移植实验研究

基本信息

批准号：
05671099
负责人：
KAMIYAMA Yasuo
金额：
$ 1.28万
依托单位：
KANSAI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671099/
关键词：
Liver failure Liver ischemia Liver transplantation Energy metabolism Redox state Auxiliary liver Liver support Hepatic coma 異所性肝移植ケトン体比ブタ

项目摘要

1. Establishment of biochemical assays of porcine blood ketone bodies. In this study, it is essential to measure the changes in blood ketone body ratio (acetoacetate/b-hydroxybutyrate, KBR) in both arterial blood of the pigs with failed liver and hepatic vein of the auxiliary transplanted liver. We have found that arterial ketone bodies of th pigs are lower than those of men, rabbits, or rats.2. Partial hepatectomy model as a recipient. Initialy, we have tried to establish a liver failure model in 90% hepatectomized pig. However, a hemodynamically stable model could not be made mainly due to large blood loss. Auxiliary liver transplantation in this model resulted in decrease of KBR in both recipient and auxiliary liver. In this model, we have failed to evaluate the availability of KBR as an index of graft failure.3. Establishment of acute liver failure induced by liver ischemia in pigs with portacaval shunt. Acute liver failure was made by the clamping of the hepatic triads for 6 hours. During liver ischemia, the levels of transaminases, arterial ammonia, and potassium were increased gradually. PT and PTT were prolonged. During the hepatic triads clamping, the arterial ketone bodies were hardly detected. Within 2 hours after the declamping, arterial KBR was recovered temporally, but the ratio continued to decline. All pigs died within 8 hours after the declamping. It was suggested that by measuring the changes in arterial KBR in this model, the efficiency of metabolic support as provided by ex-vivo perfused liver or auxiliary transplanted liver could be assessed.4. Since auxiliary liver transplantation on this animal was found to be possible without large blood loss, we have begun to evaluate the availability of KBR as an index of graft failure in this model.

1. 猪血酮体生化检测方法的建立。在本研究中，有必要测量衰竭肝猪动脉血和辅助肝移植肝静脉血酮体比（乙酰乙酸酯/b-羟基丁酸酯，KBR）的变化。我们发现猪的动脉酮体比人、兔和大鼠的动脉酮体要低。肝部分切除模型作为受体。首先，我们尝试在90%去肝猪身上建立肝衰竭模型。然而，血流动力学稳定的模型无法制作，主要原因是失血过多。本模型辅助肝移植使受体和辅助肝的KBR均降低。在这个模型中，我们没有将KBR的可用性作为移植失败的指标进行评估。门静脉分流术后猪肝缺血致急性肝衰竭的建立。夹紧肝三联管6小时，急性肝功能衰竭。肝缺血时，转氨酶、血氨、血钾水平逐渐升高。PT和PTT均延长。肝三联夹紧时，动脉酮体几乎未检出。去钳后2小时内，动脉KBR暂时恢复，但比率继续下降。所有猪均在取肢后8小时内死亡。我们认为，通过测量该模型中动脉KBR的变化，可以评估离体灌注肝或辅助移植肝提供代谢支持的效率。由于该动物的辅助肝移植可以在不大量失血的情况下进行，我们已经开始评估KBR作为移植失败指标在该模型中的可用性。