Myocardial infarction is defined as sudden ischemic death of myocardial tissue. In the clinical context, myocardial infarction is usually due to thrombotic occlusion of a coronary vessel caused by rupture of a vulnerable plaque. Ischemia induces profound metabolic and ionic perturbations in the affected myocardium and causes rapid depression of systolic function. Prolonged myocardial ischemia activates a "wavefront" of cardiomyocyte death that extends from the subendocardium to the subepicardium. Mitochondrial alterations are prominently involved in apoptosis and necrosis of cardiomyocytes in the infarcted heart. The adult mammalian heart has negligible regenerative capacity, thus the infarcted myocardium heals through formation of a scar. Infarct healing is dependent on an inflammatory cascade, triggered by alarmins released by dying cells. Clearance of dead cells and matrix debris by infiltrating phagocytes activates anti-inflammatory pathways leading to suppression of cytokine and chemokine signaling. Activation of the renin-angiotensinaldosterone system and release of transforming growth factor-β induce conversion of fibroblasts into myofibroblasts, promoting deposition of extracellular matrix proteins. Infarct healing is intertwined with geometric remodeling of the chamber, characterized by dilation, hypertrophy of viable segments, and progressive dysfunction. This review manuscript describes the molecular signals and cellular effectors implicated in injury, repair, and remodeling of the infarcted heart, the mechanistic basis of the most common complications associated with myocardial infarction, and the pathophysiologic effects of established treatment strategies. Moreover, we discuss the implications of pathophysiological insights in design and implementation of new promising therapeutic approaches for patients with myocardial infarction.
ASJC Scopus subject areas
- Physiology (medical)