Paiva Marta A, Carreira Raquel, Monteiro Pedro, Gonçalves Lino M, Providência Luís A
Unidade de Investigação Básica em Cardiologia, Serviço de Cardiologia, Hospitais da Universidade de Coimbra e Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
Rev Port Cardiol. 2005 Nov;24(11):1381-92.
Cardiac mitochondria, as the major source of energy used by the heart, play an important part in the survival of cardiomyocytes undergoing ischemia followed by reperfusion. During ischemia, cardiac mitochondria represent one of the main cellular defense mechanisms, acting as a calcium-sequestering system and maintaining levels of energy production. However, when these cellular mechanisms are overcome, loss of mitochondrial integrity leads not only to the breakdown of energy production, but also to the release of pro-apoptotic factors, thus compromising the survival of cardiac cells.
To study the impact of acute ischemia-reperfusion (IR) on myocardial mitochondrial function in an ex-vivo model of global ischemia.
Wistar rat hearts were divided into two groups: control (165 minutes of perfusion with Krebs-Henseleit solution) and ischemia-reperfusion (IR - 10 minutes perfusion, followed by 35 minutes ischemia and 120 minutes reperfusion). Various parameters of mitochondrial function were assessed: respiratory control ratio (RCR) using a Clark-type oxygen electrode, oxidative stress (using the thiobarbituric acid reactive substances [TBARS] test), and mitochondrial swelling amplitude and calcium uptake, both determined by fluorimetric methods.
All mitochondrial parameters were severely affected by IR. The IR group showed a significant decrease in RCR, which was independent of the respiratory substrate used, for each assay. There were no significant differences between the two experimental groups in TBARS production. The control group showed a trend for a decrease in mitochondrial swelling amplitude and an increase in calcium uptake compared to the IR group, in both the absence and presence of cyclosporin A.
In this study, IR significantly altered mitochondrial function (RCR, mitochondrial swelling amplitude and intramitochondrial calcium uptake). This means that during acute myocardial ischemia, every effort should be made to avoid reperfusion injury, given its deleterious consequences for coronary artery disease patients.
心脏线粒体作为心脏能量的主要来源，在经历缺血再灌注的心肌细胞存活中起着重要作用。在缺血期间，心脏线粒体是主要的细胞防御机制之一，充当钙螯合系统并维持能量产生水平。然而，当这些细胞机制被突破时，线粒体完整性的丧失不仅导致能量产生的中断，还导致促凋亡因子的释放，从而危及心脏细胞的存活。
在整体缺血的离体模型中研究急性缺血再灌注（IR）对心肌线粒体功能的影响。
将Wistar大鼠心脏分为两组：对照组（用Krebs-Henseleit溶液灌注165分钟）和缺血再灌注组（IR - 灌注10分钟，随后缺血35分钟和再灌注120分钟）。评估线粒体功能的各种参数：使用Clark型氧电极测定呼吸控制率（RCR），通过硫代巴比妥酸反应性物质（TBARS）试验测定氧化应激，以及通过荧光法测定线粒体肿胀幅度和钙摄取。
所有线粒体参数均受到IR的严重影响。IR组的RCR显著降低，每次测定均与所使用的呼吸底物无关。两组之间在TBARS产生方面没有显著差异。与IR组相比，在不存在和存在环孢菌素A的情况下，对照组的线粒体肿胀幅度均有下降趋势，而钙摄取则有增加趋势。
在本研究中，IR显著改变了线粒体功能（RCR、线粒体肿胀幅度和线粒体内钙摄取）。这意味着在急性心肌缺血期间，鉴于其对冠心病患者的有害后果，应尽一切努力避免再灌注损伤。
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