Adenosine receptors and reperfusion injury of the heart.
Adenosine receptors and reperfusion injury of the heart.
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DOI：
10.1007/978-3-540-89615-9_7
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发表时间：
2009
影响因子：
--
通讯作者：
Lasley, Robert D
中科院分区：
文献类型：
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作者：
Headrick, John P;Lasley, Robert D
腺苷是ATP的分解代谢物，在心脏中发挥多种作用，包括调节心脏对应激的反应，例如在心肌缺血和再灌注期间发生的反应。在过去的20年里，大量的证据表明，腺苷，无论是在缺血前或再灌注期间，减少可逆和不可逆的心肌损伤。后一种效应导致坏死或心肌梗死（MI）和细胞凋亡两者的减少。这些作用似乎是通过激活一种或多种G蛋白偶联受体（GPCR）介导的，这些受体被称为A1、A2A、A2B和A3腺苷受体（AR）亚型。在不同物种和模型中的实验研究表明，在缺血之前激活A1或A3 AR具有心脏保护作用。进一步的实验研究表明，在再灌注期间给予A2AAR激动剂也可以减少MI，最近的报告表明，A2BAR也可能在调节心肌再灌注损伤中发挥重要作用。尽管AR介导的心脏保护有令人信服的实验证据，但只有有限数量的临床试验检查了腺苷或基于腺苷的治疗剂在人体中的有益作用，并且这些研究的结果是不确定的。本文综述了AR介导的心脏保护作用，以及四种已知的AR在缺血再灌注实验模型中的作用。本章最后检查了迄今为止的临床试验，评估腺苷作为心脏保护剂在人类冠状动脉溶栓过程中的安全性和有效性。
Adenosine, a catabolite of ATP, exerts numerous effects in the heart, including modulation of the cardiac response to stress, such as that which occurs during myocardial ischemia and reperfusion. Over the past 20 years, substantial evidence has accumulated that adenosine, administered either prior to ischemia or during reperfusion, reduces both reversible and irreversible myocardial injury. The latter effect results in a reduction of both necrosis or myocardial infarction (MI) and apoptosis. These effects appear to be mediated via the activation of one or more G-protein-coupled receptors (GPCRs), referred to as A1, A2A, A2B and A3 adenosine receptor (AR) subtypes. Experimental studies in different species and models suggest that activation of the A1 or A3ARs prior to ischemia is cardioprotective. Further experimental studies reveal that the administration of A2AAR agonists during reperfusion can also reduce MI, and recent reports suggest that A2BARs may also play an important role in modulating myocardial reperfusion injury. Despite convincing experimental evidence for AR-mediated cardioprotection, there have been only a limited number of clinical trials examining the beneficial effects of adenosine or adenosine-based therapeutics in humans, and the results of these studies have been equivocal. This review summarizes our current knowledge of AR-mediated cardioprotection, and the roles of the four known ARs in experimental models of ischemia-reperfusion. The chapter concludes with an examination of the clinical trials to date assessing the safety and efficacy of adenosine as a cardioprotective agent during coronary thrombolysis in humans.