Mitochondrial Bioenergetics During Ischemia and Reperfusion
Mitochondrial Bioenergetics During Ischemia and Reperfusion
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DOI：
10.1007/978-3-319-55330-6_8
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发表时间：
2017-01-01
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影响因子：
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通讯作者：
Colareda, German A.
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作者：
Consolini, Alicia E.;Ragone, Maria I.;Colareda, German A.
在缺血再灌注（I/R）期间，线粒体遭受向心肌细胞供应化学能量的缺陷，但也有助于胞质离子尤其是Ca 2+的改变。它们的游离钙浓度（[Ca 2 +]m）主要取决于线粒体通过单向转运体（UCam）的进入和电化学梯度（Δ NCX）驱动的与Na+交换的挤出。心脏能量通常通过氧消耗来估计，氧消耗决定了与ATP产生和Δ △ m维持相关的代谢。然而，心脏能量消耗的更好估计是与ATP水解、代谢和结合反应相关的总热释放，其在存在或不存在氧合或灌注的情况下是可测量的。因此，对离体心脏的机械量热方法提供了评估肌肉经济性的工具。线粒体在缺血再灌注中的作用与损伤程度有关。我们研究了线粒体Ca ~（2+）转运体在大鼠心脏无血流I/R模型中的作用。本章探讨了一个综合的观点，以前的和新的结果，给线粒体的作用，心肌顿抑缺血缺氧的证据，甲状腺的改变和心脏保护策略的影响，如心脏停搏液（高钾低钙，丙酮酸盐）和植物雌激素染料木黄酮在两种性别。在30 °C或37 °C下，在流动量热计中灌注大鼠心室，以连续测量左心室压（LVP）和总热速率（Ht）。在暴露于无血流I和R之前进行药物治疗。在顿抑期间测定缺血后收缩率（PICR %）、能量（Ht）恢复和肌肉经济性（Eco：P/Ht）。线粒体（Mit）和肌浆网（SR）之间的功能相互作用进行了评价与选择性线粒体抑制剂在心脏再灌注Krebs-10 mM咖啡因-36 mM Na+。咖啡因诱导的挛缩（CIC）是由于SR Ca 2+释放，而松弛主要取决于线粒体Ca 2+摄取，因为SL-NCX和SERCA在该介质下都不起作用。曲线下面积与缺血值的比值（AUC-ΔHt/AUC-ΔLVP）估计维持CIC的能量消耗（EC）。通过抑制mNCX或通过添加需氧底物丙酮酸盐来加速CIC的松弛，而两者都增加EC。心脏停搏液（高钾低钙Krebs）和抑制UCam可减慢舒张。因此，Mit调节胞浆[Ca ~（2+）]和SR Ca ~（2+）含量。甲状腺功能亢进（HpT）和甲状腺功能减退（HypoT）虽能改善PICR，但均使CIC峰值降低，EC升高。HpT中CIC和PICR对mNCX或UCam的抑制也很敏感，提示Mit参与调节SR的储存和Ca ~（2+）释放。线粒体和SR之间的相互作用和充满活力的后果也进行了分析，染料木素在心脏暴露于I/R的影响，缺氧/复氧过程。我们的研究结果提供了证据的PICR和能量消耗的线粒体调节在击昏期间，通过Ca 2+运动。
During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca2+. Their free calcium concentration ([Ca2+]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na+(mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm. Nevertheless, a better estimation of heart energy consumption is the total heat release associated to ATP hydrolysis, metabolism, and binding reactions, which is measurable either in the presence or the absence of oxygenation or perfusion. Consequently, a mechano-calorimetrical approach on isolated hearts gives a tool to evaluate muscle economy. The mitochondrial role during I/R depends on the injury degree. We investigated the role of the mitochondrial Ca2+transporters in the energetic of hearts stunned by a model of no-flow I/R in rat hearts. This chapter explores an integrated view of previous and new results which give evidences to the mitochondrial role in cardiac stunning by ischemia o hypoxia, and the influence of thyroid alterations and cardioprotective strategies, such as cardioplegic solutions (high K-low Ca, pyruvate) and the phytoestrogen genistein in both sex. Rat ventricles were perfused in a flow-calorimeter at either 30 °C or 37 °C to continuously measure the left ventricular pressure (LVP) and total heat rate (Ht). A pharmacological treatment was done before exposing to no-flow I and R. The post-ischemic contractile (PICR as %) and energetical (Ht) recovery and muscle economy (Eco: P/Ht) were determined during stunning. The functional interaction between mitochondria (Mit) and sarcoplasmic reticulum (SR) was evaluated with selective mitochondrial inhibitors in hearts reperfused with Krebs-10 mM caffeine-36 mM Na+. The caffeine induced contracture (CIC) was due to SR Ca2+release, while relaxation mainly depends on mitochondrial Ca2+uptake since neither SL-NCX nor SERCA are functional under this media. The ratio of area-under-curves over ischemic values (AUC-ΔHt/AUC-ΔLVP) estimates the energetical consumption (EC) to maintain CIC. Relaxation of CIC was accelerated by inhibition of mNCX or by adding the aerobic substrate pyruvate, while both increased EC. Contrarily, relaxation was slowed by cardioplegia (high K-low Ca Krebs) and by inhibition of UCam. Thus, Mit regulate the cytosolic [Ca2+] and SR Ca2+content. Both, hyperthyroidism (HpT) and hypothyroidism (HypoT) reduced the peak of CIC but increased EC, in spite of improving PICR. Both, CIC and PICR inHpTwere also sensitive to inhibition of mNCX or UCam, suggesting that Mit contribute to regulate the SR store and Ca2+release. The interaction between mitochondria and SR and the energetic consequences were also analyzed for the effects of genistein in hearts exposed to I/R, and for the hypoxia/reoxygenation process. Our results give evidence about the mitochondrial regulation of both PICR and energetic consumption during stunning, through the Ca2+movement.