Myocardial ischemia and infarction: Anatomic and biochemical substrates for ischemic cell death and ventricular arrhythmias

Abstract

Myocardial ischemia is a widespread cause of morbidity and the number one cause of death in the economically developed countries of the world. In the United States, approximately 25 per cent of all deaths are at tr ibuted to hear t attacks; of these deaths, about one half occur suddenly outside the hospital setting. Although there are many possible causes of sudden unexpected death, the majority undoubtedly are cardiogenic, owing to ventricular arrhythmias that occur either in the setting of transient myocardial ischemia or in some phase of an evolving myocardial infarct. Following hospitalization for an acute myocardial infarct, the majority of deaths have anatomically definable explanations (i.e., loss of sufficient myocardium to cause cardiac pump failure or specific anatomic complications of infarction such as cardiac rupture). In addition, despite the development of many potent antiarrhythmic drugs, some patients still die of ventricular fibrillation during the acute phase of myocardial infarction; others, even after the infarct has undergone replacement by scarring, st iffer f rom recu r r en t chronic ventr icular tachycardia that can lead to hemodynamic collapse and/or ventricular fibrillation. The reduction of overall cardiac pump function in myocardial infarction may have several contributory causes; the most important cause surely is the loss of contractile mass. It has been shown, for example, that among patients with fatal myocardial infarcts, those who had died o f cardiogenic shock usually had lost at least 30 per cent and often 40 per cent or more of their left ventricular mass) Some of the gross anatomic determinants of myocardial infarct size are known, as are many subcellular biochemical and structural consequences of acute ischemic injury. However, the subcellular conditions dictating that an ischemic myocyte has become irreversibly and thus destined for necrosis have not been defined completely. The electrophysiologic explanations for most ventricular arrhythmias are reentrant conduction, enhanced automaticity of an injured focus, or triggered activity of an injured focus. 2 However, the underlying anatomic and/or biochemical explanations