Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration
Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration
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DOI：
10.1016/j.healun.2018.12.013
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发表时间：
2019-06-01
影响因子：
8.9
通讯作者：
Longnus, Sarah L.
中科院分区：
文献类型：
--
作者：
Wyss, Rahel K.;Mendez-Carmona, Natalia;Longnus, Sarah L.
背景技术背景：缺血-再灌注（IR）后的心脏保护和移植物评估对于促进循环死亡后捐献心脏移植至关重要。鉴于线粒体在IR中的关键作用，我们的目的是调查的耐受性的心脏线粒体温暖，全球缺血，并确定缺血后心脏recovery.METHODS的早期再灌注心肌相关参数的预测值：隔离，工作大鼠心脏进行0，21，24，27，30，或33分钟的温暖，全球缺血，再灌注60分钟。在再灌注60分钟时测定功能恢复（产生的压力×心率），而在再灌注10分钟时测定线粒体完整性。结果：在再灌注60分钟时，缺血>= 27分钟与无缺血相比，功能恢复降低（n = 7-8/组; p < 0.01）。细胞色素c、琥珀酸释放和线粒体Ca 2+含量随着缺血>= 27分钟而增加（p < 0.05）。与无缺血相比，缺血>= 21分钟降低了线粒体偶联、5 '-三磷酸腺苷含量、线粒体Ca 2+保留能力，并增加了氧化损伤（p < 0.05）。缺血21和27分钟与无缺血和缺血33分钟相比，来自反向电子传递的活性氧（ROS）增加（p < 0.05），而来自正向电子传递的ROS仅在缺血33分钟与无缺血时增加（p < 0.05）。线粒体偶联和5 '-三磷酸腺苷含量与心功能恢复呈正相关，细胞色素c、琥珀酸、氧化损伤和线粒体Ca ~（2+）含量与心功能恢复呈负相关（p < 0.05）。线粒体偶联、反向电子转移的ROS释放和钙潴留对早期再灌注损伤特别敏感，反映了心脏保护的潜在靶点。线粒体完整性的指标可能有助于评估循环死亡移植物移植后捐赠的适用性。(C)2018年国际心肺移植学会。All rights reserved.
BACKGROUND: Cardioprotection and graft evaluation after ischemia-reperfusion (IR) are essential in facilitating heart transplantation with donation after circulatory death. Given the key role of mitochondria in IR, we aimed to investigate the tolerance of cardiac mitochondria to warm, global ischemia and to determine the predictive value of early reperfusion mitochondria-related parameters for post-ischemic cardiac recovery.METHODS: Isolated, working rat hearts underwent 0, 21, 24, 27, 30, or 33 minutes of warm, global ischemia, followed by 60 minutes of reperfusion. Functional recovery (developed pressure x heart rate) was determined at 60 minutes of reperfusion, whereas mitochondrial integrity was measured at 10 minutes of reperfusion.RESULTS: Functional recovery at 60 minutes of reperfusion decreased with >= 27 minutes of ischemia vs no ischemia (n = 7-8/group; p < 0.01). Cytochrome c, succinate release, and mitochondrial Ca2+ content increased with >= 27 minutes of ischemia vs no ischemia (p < 0.05). Ischemia at >= 21 minutes decreased mitochondrial coupling, adenosine 5'-triphosphate content, mitochondrial Ca2+ retention capacity, and increased oxidative damage vs no ischemia (p < 0.05). Reactive oxygen species (ROS) from reverse electron transfer increased with 21 and 27 minutes of ischemia vs no ischemia and 33 minutes of ischemia (p < 0.05), whereas ROS from forward electron transfer increased only with 33 minutes of ischemia vs no ischemia (p < 0.05). Mitochondrial coupling and adenosine 5'-triphosphate content correlated positively and cytochrome c, succinate, oxidative damage, and mitochondrial Ca2+ content correlated negatively with cardiac functional recovery (p < 0.05).CONCLUSIONS: Mitochondrial dysfunction occurs with shorter periods of ischemia than cardiac dysfunction. Mitochondrial coupling, ROS emission from reverse electron transfer, and calcium retention are particularly sensitive to early reperfusion injury, reflecting potential targets for cardioprotection. Indicators of mitochondrial integrity may be of aid in evaluating suitability of donation after circulatory death grafts for transplantation. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.