Hamster Cardiomyopathy: A Genetically-Transmitted Sympathetic Dystrophy?
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.
KeywordsMyocardial Necrosis Cardiac Sympathetic Nerve Normal Hamster Cardiomyopathic Hamster Norepinephrine Turnover
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- 1.Homburger F, Baker JR, Nixon CW, Whitney R: Primary generalized polymyopathy and cardiac necrosis in an inbred line of Syrian hamsters. Med Exp (6): 339–345, 1962.Google Scholar
- 2.Bishop SP, Sole MJ and Tilley LP: Cardiomypathies. In: Andrews EJ, Ward BC and Altman NH (eds) Spontaneous Models of Human Disease. Academic Press, New York, 1979, pp 59–64.Google Scholar
- 3.Bajusz E, Homburger F, Baker JR and Bogdonoff P: Dissociation of factors influencing myocardial degeneration and cirulatory failure. Ann N.Y. Acad Sci (156): 397–420, 1969.Google Scholar
- 4.Lossnitzer K, Janke J, Hein B, Stauch M, Fleckenstein A: Disturbed myocardial calcium metabolism: a possible pathogenetic factor in the hereditary cardiomyopathy of the Syrian hamster. In: Fleckenstein A, Rona G (eds) Recent advances in studies on cardiac structure and metabolism, vol 6: Pathophysiology and morphology of myocardial cell alteration. University Park Press, Baltimore, 1975, pp 207–217.Google Scholar
- 9.Jasmin G, Bajusz E: Prevention of myocardial degeneration in hamsters with hereditary cardiomyopathy. In: Fleckenstein A, Rona G (eds) Recent advances in studies on cardiac structure and metabolism, Vol 6: Pathophysiology and morphology of myocardial cell alteration. University Park Press, Baltimore, 1975, pp 219–229.Google Scholar
- 17.Ostmann-Smith I: Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci (61): 265–272, 1981.Google Scholar