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Estimation of Graft Viability before Reperfusion Using Hepatic Microdialysate Hypoxanthine Levels in Porcine Liver Transplantation from Non-Heart-Beating Donors

在无心跳供体猪肝移植中使用肝微透析液次黄嘌呤水平评估再灌注前移植物活力

基本信息

批准号：
11557094
负责人：
KATSURAMAKI Tadashi
金额：
$ 4.16万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Non-heart-beating donors (NHBDs) are being considered for grafts in orthotopic liver transplantation (OLTX), but are not yet acceptable because of the high frequency of primary nonfunction. To establish successful liver engraftment, new strategies are needed. The aim of this study was to explore the usefull of monitoring hepatic microdialysate hypoxanthine levels during warm ischemia in cardiac arrest donors to assess liver viability before transplantation. Porcine OLTX was performed using grafts obtained from NHBDs subjected to in situ warm ischemia (0, 30 and 60 min). In the donor operation, hepatic interstitial hypoxanthine levels were measured during warm ischemia by a microdialysis method. All of the 0-min group, 6 of 13 pigs in the 30-min group, and 1 of 4 pigs in the 60-min group survived more than 7 days. Significant increases of hypoxanthine levels were seen dependent on warm ischemic time. In the 30-min group, hypoxanthine levels were significantly higher in the pigs that died than in those that survived, and correlated with the adenosine triphosphate, aspartate aminotransferase, and lactate dehydrogenase levels of recipients. Histological examination revealed that graft injury was severe in the pigs with higher hypoxanthine levels. Marked interstitial formation of hypoxanthine in cardiac arrest donors may indicate the degree of warm ischemic injury, indirect evidence of increased free radicals after reperfusion, or a substantial loss of the adenylate pool. These observations suggest that hepatic microdialysate hypoxanthine levels during warm ischemia in the NHBDs were correlated with liver viability before transplantation and that prediction of the viability of the graft may be possible by using this method.

非心脏跳动供体（NHBDs）被认为是原位肝移植（OLTX）中的移植物，但由于原发性无功能的高频率尚未被接受。为了建立成功的肝移植，需要新的策略。本研究的目的是探讨在心脏骤停供者热缺血期间监测肝微透析次黄嘌呤水平对移植前评估肝脏活力的有用性。猪OLTX采用原位热缺血（0,30和60分钟）的NHBDs移植物进行。在供体手术中，用微透析法测定热缺血时肝间质次黄嘌呤水平。0-min组、30-min组13头猪中有6头、60-min组4头猪中有1头存活超过7天。次黄嘌呤水平的显著增加与热缺血时间有关。在30分钟组中，死亡猪的次黄嘌呤水平明显高于存活猪，并且与受体的三磷酸腺苷、天冬氨酸转氨酶和乳酸脱氢酶水平相关。组织学检查显示，高次黄嘌呤水平的猪移植物损伤严重。心脏骤停供者间质中明显的次黄嘌呤形成可能表明热缺血损伤的程度，再灌注后自由基增加的间接证据，或腺苷酸池的大量损失。这些观察结果表明，NHBDs在热缺血期间的肝微透析次黄嘌呤水平与移植前的肝脏活力相关，并且可以通过这种方法预测移植物的活力。