Apoptotic cell death in arrhythmogenic right ventricular cardiomyopathy - A comparative study with idiopathic sustained ventricular tachycardia

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a specific heart muscle disease of unknown etiology characterized by; fatty and fibrofatty r eplacement of the right ventricular myocardium. It often manifests life-thr eatened ventricular arrhythmias. Previous studies have hypothesized that my ocyte apoptosis contributes to the myocyte cell loss and fatty change in AR VC and may be induced by recurrent ventricular tachycardia (VT). We examine d whether these progressive pathological changes result from apoptotic cell death in both autopsied and biopsied right ventricular myocardium from 35 patients with ARVC by using in situ terminal deoxynucleotidyl transferase a ssay (TUNEL) and agarose gel electrophoresis. We also studied the biopsied myocardium from 30 patients with idiopathic sustained VT whose origin was t he outflow tract of the right ventricle. TUNEL-positive cells indicating DN A fragments were observed in some cardiomyocytes and fibroblasts in ARVC, b ut the numbers of TUNEL-positive myocytes were very low in idiopathic VT. D NA laddering was confirmed in two autopsied cases in ARVC, but not in a non -cardiac case who died. These results suggest that at least some cardiomyoc ytes and fibroblasts are subjected to apoptosis in ARVC, leading to the los s of myocardium with characteristic pathological changes and subsequently p rogressive cardiomyopathy. Furthermore, the apoptotic process may not resul t from myocardial ischemia due to repetitive VT.