Myocardial stunning: mechanisms, molecular insights, and gaps in knowledge

Myocardial stunning, characterized by transient post-ischemic contractile dysfunction despite the restoration of coronary blood flow, has been a pivotal subject of cardiovascular research. Initially perceived as a consequence of irreversible myocardial damage and fibrosis, the concept evolved in the 1970s when studies revealed that reperfusion could salvage ischemic myocardium, leading to therapies like thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting. The phenomenon of myocardial stunning was first detailed by Heyndrickx et al. and later termed by Braunwald and Kloner, challenging previous views by demonstrating that reperfusion can cause temporary yet reversible dysfunction without necrosis. Extensive research elucidated mechanisms involving reactive oxygen species (ROS), calcium overload, and impaired excitation-contraction coupling. Recent advances in proteomics and phospho-proteomics identified molecular changes linked to contractile dysfunction, extracellular matrix damage, and apoptosis. The role of epigenetics has also garnered attention for its potential to influence myocardial stunning and offer therapeutic avenues. This review comprehensively explores the historical and mechanistic landscape of myocardial stunning, recent molecular insights, and its clinical relevance. Future research directions emphasize advanced proteomic and phosphor-proteomic analyses, epigenetic mechanisms, clinical translation, non-invasive diagnostics, ROS role clarification, ischemia preconditioning impacts, and integrative systems biology. Addressing these areas will enhance our understanding and lead to improved therapeutic strategies for ischemic heart disease.