Hamster Cardiomyopathy: A Genetically-Transmitted Sympathetic Dystrophy?

Abstract

The cardiomyopathic Syrian hamster is a reproduceable paradigm of a genetically transmitted congestive cardiomyopathy. The cardiac disease first becomes manifest in juvenile hamsters (30–60 days old) with the development of patchy myocardial necrosis. Previous work has shown the myocardium of neonatal myopathic hamsters to be hypersensitive to the cardiotoxic effects of the catecholamines. Perfusion of hamster hearts, in vivo, with liquid silicone rubber has revealed numerous areas of microvascular constriction in the cardiomyopathy; both the microvascular alterations and the myocardial necrosis could be abolished by pretreating juvenile hamsters with verapamil. In this study we examine further the pathogenesis of the cardiomyopathy. Juvenile hamsters of various cardiomyopathic (Bio 14.6, 40.54, 53.58, 82.62) and control (Bio 2.4, 87.20, XXB, RB) strains were studied. Cardiac norepinephrine turnover in each of the cardiomyopathic strains was greater than that for any of the control strains (Range 119–223 ng/g/hr and 35–108 ng/g/hr respectively). The administration of prazosin an α₁ antagonist for two weeks had a marked ameliorating effect (area of micronecrosis 8.8% in untreated vs 0.66% in treated). Thus hamster cardiomyopathy appears to depend on the genetic transmission of a hypersensitivity of both vascular smooth muscle cells and cardiac myocytes to catecholamine stimulation. With postnatal maturation of the sympathetic nervous system there is an increase in cardiac neural norepinephrine release which leads to microvascular spasm which in turn, by subjecting the hypersusceptible myocyte population to repeated episodes of ischemia and reperfusion, leads to myocyte loss and compensatory hypertrophy in the remaining myocardial cells. This process is obviated by calcium entry blockers or markedly ameliorated by α antagonists.