Myocyte destruction in inflammatory cardiomyopathy - Apoptosis or necrosis?

Cell death can be induced by 2 different mechanisms: necrosis and apoptosis . Necrosis, on the one hand, is usually caused by unphysiological stress fa ctors such as hyperthermia or hypoxia, apoptosis, on the other hand, is par t of the normal organ development and controls for example immune responses . Morphologically, necrosis is characterized by swelling of cells and their organelles leading to the disruption of the cell membrane, which in turn c auses an inflammatory reaction in the surrounding tissue. Morphological and biochemical criteria (Figure 1, Table 1) of apoptosis are the condensation of chromatin leading to the development of apoptotic bodies or membrane-en closed vesicles containing oligonucleosomal DNA fragments. Important diagnostic tools of eel death (Table 2), such as the TUNEL test ( Figure 2) or gel electrophoresis of extracted DNA (Figure 3) are based on t he above mentioned biochemical characteristics, but a reliable differentiat ion of apoptotic versus necrotic processes is not always possible. Experimental studies in animals and studies in various diseases of the card iovascular system were able to show that apoptosis in myocytes can be induc ed, an issue that has long been discussed controversially Ischemia, reperfu sion, and myocardial infarction were also shown to lead to apoptosis in car diomyocytes, whereas cell destruction was caused mainly by necrosis. Severa l authors (Table 3) demonstrated apoptotic indices in cardiomyocytes of pat ients with dilatated cardiomyopathy, arrhythmogenic right ventricular cardi omyopathy and patients with acute infarction from 0.25 to 35% by the use of the TUNEL test. Others were able to demonstrate an elevated expression of Fas-receptor in cells of atheroslerotic plaques in patients with atheroscle rosis and high indices of apoptotic cardiomyocytes in patients with chronic heart failure. We investigated endomyocardial biopsies of patients with inflammatory cardi omyopathy, DCM without inflammatory reaction but the presence of adenoviral or cytomegaloviral genome and idiopathic DCM using the TUNEL test. The per centage of apoptotic cardiomyocytes in biopsies of patients with DCMi was 1 .03 and in biopsies of patients with adenoviral genome 0.25, whereas in all other groups no apoptosis was found. If apoptosis plays a major role in myocardial diseases such as heart failur e, arrhythmia and others, blocking this mechanism will have to be considere d as a therapeutical strategy. Therefore, studies on the extent of apoptoti c processes in diseased versus healthy cardiac tissue are of great importan ce.