| Myocardial cell death occurs following many stresses to the heart including mechanical stretch, cardiomyopathy, myocardial infarction and ischemia, either with or without reperfusion. Although the majority of the literature to date indicates that necrosis is the predominant mechanism of cell death within the heart, recent evidence also points to apoptosis under these conditions. The mechanisms underlying cardiomyocyte cell death are particularly relevant to current studies of ischemic heart disease, including both ischemia alone and ischemia with subsequent reperfusion. During these pathophysiologic states, levels of the inflammatory cytokine TNFα are elevated and may mediate the aspects of myocardial cell death and survival. Previous studies have suggested roles for TNFα in many human cardiac disease processes including congestive heart failure, myocarditis, ischemic heart disease, dilated cardiomyopathy, sepsis induced cardiomyopathy, and apoptosis. Although roles for this cytokine have been established, both in myocardial ischemia and ischemia reperfusion, how the multiple TNFα signaling events result in the overall effect is not known. This review will discuss the putative role of this cytokine in cardiomyocyte cell death following an ischemic insult and attempt to link these roles to the specific myocardial injury that ensues from the insult and the available levels of ATP within the myocardium. |
