The Coronary Circulation as a Target of Cardioprotection

Myocardial ischemia/reperfusion injury affects not only the cardiomyocyte compartment but also all other cellular compartments, and the coronary circulation has a central role in it. Acute myocardial infarction most often arises from atherosclerotic plaque rupture/erosion with superimposed thrombosis (type 1 myocardial infarction). However, in the absence of coronary atherosclerosis, coronary vasospasm and endothelial dysfunction may also precipitate acute myocardial infarction (type 2). Reperfusion of the occluded coronary artery with restoration of coronary blood flow not only terminates myocardial ischemia but also inflicts additional injury, and interventional or surgical revascularization may actually induce periprocedural myocardial infarction (types 4 and 5 myocardial infarction). The spatial and temporal evolution of coronary occlusion and reperfusion determine not only the size of the affected myocardial region but also the nature of the outcome from myocardial ischemia/reperfusion, that is, reversible (stunning) or irreversible (infarction) injury and, vice versa, also protection from injury (hibernation and conditioning). Cardioprotective interventions reduce myocardial ischemia/reperfusion injury, notably infarct size, but also arrhythmias, left ventricular dysfunction, and coronary vascular impairment. A complex signal transduction cascade underlies the cardioprotective effects of ischemic preconditioning, ischemic postconditioning, and remote ischemic conditioning. A variety of drugs that often recruit signaling steps of conditioning strategies have been used to achieve cardioprotection. The translation of cardioprotection from animal experiments to clinical practice has been difficult and largely disappointing to date, despite several positive proof-of-concept studies in humans. Neglect of the coronary circulation as a victim of myocardial ischemia/reperfusion injury and as a target for cardioprotection may have contributed to the lack of translation of cardioprotection to clinical practice. A particular problem is acute myocardial infarction in women. On the one hand, the female heart is more resistant to myocardial ischemia/reperfusion than the male heart. On the other hand, women have nonobstructive coronary artery disease more often than men, and coronary vasomotion (coronary vasospasm, endothelial dysfunction, and microvascular dysfunction) may play a greater role in precipitating acute myocardial infarction in women.