Viral myocarditis: a paradigm for understanding the pathogenesis and treatment of dilated cardiomyopathy.
Although an etiologic link between viral myocarditis and idiopathic dilated cardiomyopathy has long been recognized, the actual extent of this relation has been uncertain. In this review, we examine recent developments in the molecular analysis of endomyocardial biopsy specimens, particularly techniques for gene amplification, which have unequivocally confirmed this relation and given us some insight into its significance. 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 cardiomyopathic hamsters, rats and humans with hypertension and diabetes, rats after acute brain injury and models of Chagas' disease. Treatment of 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 genetic hamster model and a murine model of myocarditis. There is some suggestion that digitalis, though beneficial during cardiac decompensation, may actually be detrimental when administered during the early stages of myocardial disease. These experiments have led to a new paradigm for the pathogenesis of cardiomyopathy after viral myocarditis, as well as a general hypothesis for the pathogenesis of some types of dilated cardiomyopathy. They also suggest that the selection of therapeutic agents for some forms of dilated cardiomyopathy may differ significantly between the early and late stages of the disease.
Centre For Cardiovascular Research, University of Toronto, Ontario, Canada.
M J
MJ
Sole
P
P
Liu
D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D009205:Myocarditis / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D014777:Virus Diseases / Q000150:complications* / Q000175:diagnosis / Q000628:therapy
D004279:DNA, Viral