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Cardioprotection From Ischemia/Reperfusion Injury – Basic and Translational Research –

机译:心脏保护免受缺血/再灌注损伤–基础和转化研究–

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Because ischemic heart diseases (IHDs) are a major cause of mortality and heart failure, novel therapeutic approaches are expected to improve the clinical outcomes of patients with IHDs such as acute myocardial infarction and ischemic heart failure. Brief episodes of nonlethal ischemia and reperfusion before sustained ischemia or at the onset of reperfusion can reduce ischemia-reperfusion injury. These ischemic conditioning phenomena are termed "ischemic preconditioning" and "ischemic postconditioning", respectively. Furthermore, brief episodes of nonlethal ischemia and reperfusion applied to the organ or tissue distal to the heart reduce myocardial infarct size, known as "remote ischemic conditioning". The cardioprotection afforded by these ischemic conditionings can be used to treat patients with acute myocardial infarction or cardiac operations. Extensive research has determined that autacoids (eg, adenosine, bradykinin opioid) and cytokines, their respective receptors, kinase signaling pathways and mitochondrial modulation are involved in ischemic conditioning. Modification of these factors by pharmacological agents mimics the cardioprotection by ischemic conditioning and provides a novel therapeutic intervention for IHDs. Here, the potential mechanisms of ischemic conditioning and its "proof-of-concept" translational studies are reviewed. In the near future, large, multicenter, randomized, placebo-controlled, clinical trials will be required to determine whether pharmacological and ischemic conditioning can improve the clinical outcomes of patients with IHDs. ( Circ J 2012; 76: 1074-1082)
机译:由于缺血性心脏病(IHD)是导致死亡和心力衰竭的主要原因,因此新的治疗方法有望改善IHD患者的临床结局,例如急性心肌梗塞和缺血性心力衰竭。非致命性缺血和再灌注的短暂发作在持续缺血之前或在再灌注开始时可以减少缺血-再灌注损伤。将这些缺血性调节现象分别称为“缺血性预处理”和“缺血性后调节”。此外,对心脏远端的器官或组织施加的非致死性缺血和再灌注的短暂发作减小了心肌梗塞的大小,称为“远程缺血调节”。这些缺血性调节条件提供的心脏保护作用可用于治疗急性心肌梗塞或心脏手术患者。广泛的研究已经确定,autacoids(例如腺苷,缓激肽阿片类药物)和细胞因子,它们各自的受体,激酶信号传导途径和线粒体调节都参与了缺血性调节。通过药理学试剂对这些因子的修饰模拟了缺血条件对心脏的保护作用,并为IHD提供了一种新颖的治疗手段。在这里,对缺血性调节的潜在机制及其“概念验证”的翻译研究进行了综述。在不久的将来,将需要进行大型,多中心,随机,安慰剂对照的临床试验,以确定药理和缺血条件是否可以改善IHD患者的临床结局。 (Circ J 2012; 76:1074-1082)

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