Apoptosis: measurement and technical issues.

In this short review article we discuss the many uncertainties with the estimation of the relevance of data on the rate of apoptotic cell death in the myocardium. 1. The time course and duration of the apoptotic cascade is still almost completely unknown, in cardiac tissue as well as in myocytes in culture. 2. The mode of removal of dead cells from their connections to neigbouring myocytes at the intercalated disc is still unidentified. 3. At what step in the apoptotic cascade is this process still reversible? 4. Numerous methods exist for the identification of apoptotic cells. However, their sensitivity and specificity vary and issues such as different dwell times of cells with DNA fragmentation further complicate the reliability of apoptotic rates obtained. 5. Statistical principles should be applied for the quantification of apoptotic cells. Only after clarification of these technical issues an unequivocal answer to the problem of apoptotic myocyte loss in different cardiac pathologies can be expected.