Yusof Nur Liyana Mohammed, Yellon Derek M, Davidson Sean M
The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia.
Basic Res Cardiol. 2025 Jun 7. doi: 10.1007/s00395-025-01120-1.
Although reperfusion therapy such as percutaneous coronary intervention and thrombolysis have been implemented in clinical practise as treatments for acute myocardial infarction (AMI) since the 1970s, patients continue to experience high rates of morbidity and mortality. Coronary reperfusion is effective as it limits infarction. However, it induces significant myocardial injury, known as ischaemia-reperfusion (IR) injury. Sustained depletion of cellular adenosine triphosphate (ATP) leading to intracellular calcium (Ca) overload ultimately lead to cardiomyocyte death during ischaemia. Reperfusion enables resynthesis of ATP, but if this occurs whilst Ca remains elevated, it induces excessive cardiomyocyte contracture, known as hypercontracture. Irreversible myocardial injury caused by hypercontracture is often accompanied by histological findings such as wavy myocardial fibres, and more profoundly, contraction band necrosis, identified by the presence of dense eosinophilic bands within the cardiomyocytes. The presence of hypercontracture imposes deleterious effects on both cardiac function and clinical outcomes in individuals experiencing AMI. The potential cardioprotective benefits of inhibiting hypercontracture following IR injury have been demonstrated in animal models, however therapies suitable for clinical application are yet to be developed. This article reviews the pathogenesis and clinical manifestation of hypercontracture in cardiomyocytes during AMI. In addition, the discussion highlights the challenges of translating robust pre-clinical data into successful clinical therapeutic approaches.
自20世纪70年代以来，经皮冠状动脉介入治疗和溶栓等再灌注疗法已在临床实践中用于治疗急性心肌梗死（AMI），但患者的发病率和死亡率仍然很高。冠状动脉再灌注可有效限制梗死范围。然而，它会引发显著的心肌损伤，即缺血再灌注（IR）损伤。在缺血期间，细胞三磷酸腺苷（ATP）持续消耗导致细胞内钙（Ca）超载，最终导致心肌细胞死亡。再灌注使ATP得以重新合成，但如果在Ca仍处于升高状态时发生这种情况，就会诱发过度的心肌细胞挛缩，即超挛缩。超挛缩引起的不可逆心肌损伤通常伴有组织学表现，如心肌纤维呈波浪状，更严重的是出现收缩带坏死，表现为心肌细胞内有致密的嗜酸性带。超挛缩的存在对AMI患者的心脏功能和临床结局均有不利影响。在动物模型中已证明抑制IR损伤后超挛缩具有潜在的心脏保护作用，但适合临床应用的疗法尚未开发出来。本文综述了AMI期间心肌细胞超挛缩的发病机制和临床表现。此外，讨论还强调了将有力的临床前数据转化为成功的临床治疗方法所面临的挑战。
