EVIDENCE OF APOPTOSIS IN ARRHYTHMOGENIC RIGHT-VENTRICULAR DYSPLASIA

Background Arrhythmogenic right ventricular dysplasia, a disorder that may lead to severe ventricular arrhythmias and sudden death, is chara cterized by the progressive replacement of myocardial cells by fat and fibrous tissue. We examined whether the loss of myocardial cells in t his disease could result from cell death by apoptosis (programmed cell death). Methods Specimens obtained at autopsy from the right ventricu lar myocardium of eight patients with arrhythmogenic right Ventricular dysplasia and four age-matched normal subjects were analyzed. To iden tify individual cells undergoing apoptosis, we performed in situ end-l abeling of fragmented DNA on paraffin sections using biotinylated deox yuridine triphosphate and the enzyme terminal deoxynucleotidyl transfe rase, We also examined the level of expression of CPP-32, a cysteine p rotease required for apoptotic cell death in mammalian cells, using im munohistochemical techniques. Results Apoptosis was detected in the ri ght ventricular myocardium of six of the eight patients with arrhythmo genic 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 tha t apoptotic myocardial cell death occurs in arrhythmogenic right ventr icular dysplasia and may contribute to the loss of myocardial cells in this disorder. (C) 1996, Massachusetts Medical Society.