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Previous Volume 335:1190-1197 October 17, 1996 Number 16 Next

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ABSTRACT

Background Arrhythmogenic right ventricular dysplasia, a disorder that may lead to severe ventricular arrhythmias and sudden death, is characterized by the progressive replacement of myocardial cells by fat and fibrous tissue. We examined whether the loss of myocardial cells in this disease could result from cell death by apoptosis (programmed cell death).

Methods Specimens obtained at autopsy from the right ventricular myocardium of eight patients with arrhythmogenic right ventricular dysplasia and four age-matched normal subjects were analyzed. To identify individual cells undergoing apoptosis, we performed in situ end-labeling of fragmented DNA on paraffin sections using biotinylated deoxyuridine triphosphate and the enzyme terminal deoxynucleotidyl transferase. We also examined the level of expression of CPP-32, a cysteine protease required for apoptotic cell death in mammalian cells, using immunohistochemical techniques.

Results Apoptosis was detected in the right ventricular myocardium of six of the eight patients with arrhythmogenic right ventricular dysplasia and was absent in the controls. High levels of expression of CPP-32 were associated with positive in situ end-labeling of fragmented DNA.

Conclusions These results indicate that apoptotic myocardial cell death occurs in arrhythmogenic right ventricular dysplasia and may contribute to the loss of myocardial cells in this disorder.

Source Information

From the Centre de Rythmologie et de Stimulation Cardiaque, Hôpital Jean Rostand, Ivry-sur-Seine (Z.M., F.F., R.F., G.F.); INSERM Unité 141, Hôpital Lariboisière, Paris (Z.M., A.T.); and the Service d'Anatomie et de Cytologie Pathologiques, Hôpital Raymond Poincaré, Garches (M.D.) — all in France.

Address reprint requests to Dr. Mallat at the Centre de Rythmologie et de Stimulation Cardiaque, Hôpital Jean Rostand, 39, rue Jean-le-Galleu, 94200 Ivry-sur-Seine, France.

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