InVivoEvidence ofApoptosis inArrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic rightventricular cardiomyopathy (ARVC)isa primaryheartmuscledisease characterizedbyprogressive atrophyoftheright ventricular myocardium withfibro-fatty replacement andtherisk ofelectrical instability andsuddendeath. Thedisease isoftenfamilial andtheaetiopathogenesis isstill unknown.Recentlyapoptosis (genetically determined celideath) was postulated toaccountforprogressive lossofmyocardium. Toestablish whetherapoptosis ispresentinARVC,right ventricular endomyocardial biopsies from20patients withclinical andhistologicaldiagnosis ofARVC were examinedby electron microscopyand terminal deoxynucleotidyl transferase-mediated dUTP-biotinnick end-labeling method(TUtNEL). Apoptotic indexwas calculated as thepercentageofpositive nuclei insections stained byTUNEL.Celiproliferation activity was alsoassessed byargyrophilic staIning of thenucleolar organizer region (AgNOR)andMIB-1antibody analysis. Twenty biopsies takenfrompatients duringmonitoring of cardiac transplantation (grade 0rejection) served as control. Occurrence ofapoptosis was correlated with clinical history duration andthepresence ofacute symptoms andsignslikeangina,pyrexia, erythrocytesedimentation rateandcreatine phosphokinase elevation, as weli as STsegmentelevation on basal electrocardiogram. Electron microscopy andTUNEL revealed presence ofapoptotic myocytesinseven