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American Journal of Pathology, Vol 148, 141-149, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure

VG Sharov, HN Sabbah, H Shimoyama, AV Goussev, M Lesch and S Goldstein
Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA.

It is often speculated that progressive deterioration of left ventricular function in heart failure is due to ongoing loss of viable cardiocytes. In this study, we examined the possibility that cardiocyte loss in heart failure may be due, in part, to apoptosis, an active process of gene-directed cellular self-destruction. Studies were performed in left ventricular tissue obtained from 10 dogs with chronic heart failure produced by multiple intracoronary microembolizations (left ventricular ejection fraction 27 +/- 1%) and from 5 normal dogs. Evidence for cardiocyte apoptosis was based on transmission electron microscopy criteria and on in situ immunohistochemical labeling of nuclear DNA fragmentation. There was no evidence of apoptotic cardiocytes in normal dogs. Features of cardiocyte apoptosis were observed in dogs with heart failure primarily in regions bordering old infarcts. Electron microscopic features of cardiocyte apoptosis included (1) intact sarcolemma and inner organelles in the presence of compaction and segregation of nuclear chromatin into sharply delineated masses that about the nuclear envelope, (2) intact sarcolemma in the presence of cytoplasm shrinkage, blebbing, and nuclear fragmentation, and (3) intact sarcolemma in the presence of complete disorganization of inner organelles and disappearance of nucleolemma. A count of all of the apoptotic bodies positively labeled for nuclear DNA fragments showed that 11% were of cardiocyte origin confirmed by positive labeling with striated muscle antimyosin antibody. We conclude that morphological and biochemical features of cardiocyte apoptosis exist in the left ventricular myocardium of dogs with chronic heart failure.


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