Abstract

Based on positive identification of DNA replication and mitotic division in cardiomyocytes isolated from failing hearts, it has been proposed that adult ventricular cardiomyocytes can gain the capacity to proliferate with progression of heart failure. However, due to the lack of a reliable method to distinctly image individual cardiac cells within the myocardial syntitium, such a concept still remains largely controversial. In the present study, we used laser confocal microscopy, to image cross-sections of intact myocardium stained with fluorescein-conjugated wheat germ agglutinin and propidium iodide. This approach allowed to clearly separate the profile of individual myocytes within cardiac tissue sections. We found that in the left ventricles of dogs, subjected to tachycardia-induced cardiomyopathy, the number of cells was significantly increased in both longitudinal and transversal sections. Treatment with the angiotensin-converting enzyme inhibitor, enalapril, reversed these changes to values similar to those found in controls. Therefore, this study provides evidence, at the in situ level, for cellular hyperplasia in heart failure. This supports the more general notion that adult cardiomyocytes may not be terminally differentiated, and that an increase in cell number could contribute to the increase in left ventricular mass observed with progression of disease.

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