The Heart Hospital, University College London Hospitals, 16-18 Westmoreland Street, W1G 8PH, London, UK.
Eur Heart J. 2013 Jun;34(23):1714-22. doi: 10.1093/eurheartj/eht090. Epub 2013 Mar 27.
Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.
冠心病（CHD）是欧洲死亡和残疾的主要原因。对于出现急性 ST 段抬高型心肌梗死（STEMI）的患者，及时进行心肌再灌注治疗，无论是溶栓治疗还是直接经皮冠状动脉介入治疗（PPCI），都是限制心肌梗死（MI）面积、保护左心室收缩功能和减少心力衰竭发生的最有效治疗方法。尽管如此，STEMI 患者的发病率和死亡率仍然很高，需要新的治疗干预措施来改善该患者群体的临床结局。矛盾的是，心肌再灌注本身可诱导心肌细胞死亡——这种现象被称为“心肌再灌注损伤（RI）”，其不可逆的后果包括微血管阻塞和心肌梗死。不幸的是，目前尚无有效的治疗方法可预防 STEMI 患者的心肌 RI，使其成为心脏保护的一个重要剩余靶点。先前尝试将心脏保护疗法（抗氧化剂、钙通道阻滞剂和抗炎剂）转化为临床应用以减少 RI，但均未成功。对 RI 发病机制的深入了解，已经确定了几种有前途的机械（缺血后处理、远程缺血预处理、治疗性低温和高氧血症）和药理学（心房利钠肽、环孢素 A 和 exenatide）治疗策略，用于预防心肌 RI，其中许多在初步的原理验证临床研究中显示出了希望。本文综述了心肌 RI 的病理生理学，并强调了未来可能用于预防 RI 和改善 CHD 患者临床结局的潜在治疗干预措施。
