Cardiomyocyte apoptosis in acute and chronic conditions

Abstract

Myocytes can die by necrosis or by apoptosis and the characteristics of both kinds of cell death are so typical that a differentiation can be made by histological and molecular-biological methods using electron microscopy, dUTP labeling with fluorescence or peroxidase stainig (TUNEL) and the DNA laddering method. However, the problem of quantification of apoptotic cells has not been completely solved because of lack of standardization as well as uncritical use and interpretation of the TUNEL method. Equally, quantification of apoptotic cells is not optimal until now because of three reasons: methodological (overinterpretation of results, no differentiation between myocytes and non-myocytes), experimental (global or regional acute ischemia, chronic conditions such as heart failure or hibernating myocardium), and interpretation (unknown time period for the completion of apoptosis). This problem is reflected in the large differences in incidence of apoptosis reported. Our own data show that in dog myocardium made globally ischemic for 90 min, 8% of the myocytes showed a positive staining for apoptosis (TUNEL method) after 6 h of reperfusion. Despite these results the question of reperfusion injury and the influence of apoptosis still remains open, because it can not be excluded until now that the apoptotic process is initiated during the ischemic period. Studies in hibernating myocardium and chronic heart failure show a similar situation, because of a wide variation of numbers of apoptotic cells and the limited possibility to investigate human tissue. There is no doubt that apoptosis plays an important role in chronic pathophysiological situations such as heart failure and hibernating myocardium but the importance of apoptosis in the acute situation of ischemia/reperfusion still has to be clarified.