Mitochondrial transplantation for myocardial protection in ex-situ-perfused hearts donated after circulatory death
Mitochondrial transplantation for myocardial protection in ex-situ-perfused hearts donated after circulatory death
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DOI：
10.1016/j.healun.2020.06.023
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发表时间：
2020-11-01
影响因子：
8.9
通讯作者：
McCully, James D.
中科院分区：
文献类型：
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作者：
Guariento, Alvise;Doulamis, Ilias P.;McCully, James D.
背景技术背景：循环性死亡后的捐献（DCD）提供了一个额外的心脏移植物来源，有可能扩大供体库，但由于缺血的影响而受到限制。在这项研究中，我们探讨了线粒体移植，以提高心肌功能的DCD hearts.METHODS：循环死亡诱导约克郡猪（40-50公斤，n = 29）的机械通气停止。热缺血20分钟后，给予心脏停搏液。然后在异位血液灌注系统上对心脏进行再灌注。再灌注15分钟后，心脏接受单独的载体（载体[VEH]，10 ml; n = 8）或含有自体线粒体的载体（线粒体载体作为单次注射[MT]，10 ml中5 x 10（9），n = 8）。另一组心脏（连续注射线粒体[MTS]; n = 6）在异位心脏灌注2小时后接受第二次注射线粒体（10 ml中5 x 10（9）），并再灌注2小时。A Sham组（假心脏; n = 6）未发生任何热缺血。在再灌注4 h结束时，MT和MTS组显示出显著增加的左心室/心室峰发展压力（p = 0.002）、最大左心室/心室压力升高（p < 0.001）、缩短分数（p <0.001）、心肌耗氧量（p = 0.004）。MT组和MTS组与VEH组相比，CT大小显著减小（p < 0.001）。在整个reperfusion.CONCLUSIONS：线粒体移植显着保留心肌功能和耗氧量在DCD心脏，从而提供了一个可能的选择，扩大心脏供体库之间或组内动脉乳酸水平没有差异。(C)2020年国际心肺移植学会。All rights reserved.
BACKGROUND: Donation after circulatory death (DCD) offers an additional source of cardiac allog-rafts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts.METHODS: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 x 10(9) in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MTS]; n = 6) received a second injection of mitochondria (5 x 10(9) in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia.RESULTS: At the end of 4 hours of reperfusion, MT and MTS groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MTS groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion.CONCLUSIONS: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.