EVIDENCE OF CARDIOCYTE APOPTOSIS IN MYOCARDIUM OF DOGS WITH CHRONIC HEART-FAILURE

It is often speculated that progressive deterioration of left ventricu lar function in heart failure is due to ongoing loss of viable cardioc ytes, 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 failu re produced by multiple intracoronary microembolizations (left ventric ular ejection fraction 27 +/- 1%) and from 5 normal dogs, Evidence for cardiocyte apoptosis was based on transmission electron microscopy cr iteria and on in situ immunohistochemical labeling of nuclear DNA frag mentation. There was no evidence of apoptotic cardiocytes in normal do gs. Features of cardiocyte apoptosis were observed in dogs with heart failure primarily in regions bordering old infarcts. Electron microsco pic features of cardiocyte apoptosis included (1) intact sarcolemma an d inner organelles in the presence of compaction and segregation of nu clear chromatin into sharply delineated masses that abut the nuclear e nvelope, (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 disappea rance of nucleolemma, A count of all of the apoptotic bodies Positivel y 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.