VIRAL MYOCARDITIS - A PARADIGM FOR UNDERSTANDING THE PATHOGENESIS ANDTREATMENT OF DILATED CARDIOMYOPATHY

Although an etiologic link between viral myocarditis and idio pathic d ilated cardiomyopathy has long been recognized, the actual extent of t his relation has been uncertain. In this review, we examine recent dev elopments in the molecular analysis of endomyocardial biopsy specimens , particularly techniques for gene amplification, which have unequivoc ally confirmed this relation and given us some insight into its signif icance. In addition, we show that viral myocarditis in a murine model is associated with spasm of the coronary microvasculature, leading to myocyte necrosis, fibrosis, calcification and cardiac dilation. These findings are similar to those seen in the hearts of genetically cardio myopathic hamsters, rats and humans with hypertension and diabetes, ra ts after acute brain injury and models of Chagas' disease. Treatment o f microvascular spasm with verapamil, captopril or alpha(1)-adrenergic blocking agents appears to interrupt this pathway and has been shown to markedly impede the evolution of dilated cardiomyopathy in the gene tic hamster model and a murine model of myocarditis. There is some sug gestion that digitalis, though beneficial during cardiac decompensatio n, may actually be detrimental when administered during the early stag es of myocardial disease. These experiments have led to a new paradigm for the pathogenesis of cardiomyopathy after viral myocarditis, as we ll as a general hypothesis for the pathogenesis of some types of dilat ed cardiomyopathy. They also suggest that the selection of therapeutic agents for some forms of dilated cardiomyopathy may differ significan tly between the early and late stages of the disease.