Disturbed myocardial calcium metabolism: a possible pathogenetic factor in the hereditary cardiomyopathy of the Syrian hamster.
In the BIO 8262 inbred strain of cardiomyopathic Syrian hamsters, a latent disturbance of their myocardial calcium metabolism could be evidenced. Whereas the myocardial calcium content of untreated young cardiomyopathic hamsters with prenecrotic hearts did not differ from that of healthy control animals, it was distinctly elevated 6 hours after injection of isoproterenol (1 mg/kg body weight s.c.) in cardiomyopathic animals remaining unchanged in healthy controls. However, the same dose of isoproterenol induced elevated myocardial 45Ca uptake in both strains, although that of the cardiomyopathic hearts was distinctly greater. Later, during the stage of spontaneous progressive necrotization of the hearts, a spontaneously increased myocardial uptake of 45Ca and calcium content became manifest. By combined treatment with isoproterenol and verapamil, a substance which is known to decrease the calcium conductivity of myocardial cell membranes without blocking beta-adrenergic receptors, the isoproterenol-stimulated 45Ca uptake by prenecrotic cardiomyopathic hearts as well as the increase of their calcium content could be inhibited. Long-term treatment with verapamil alone beginning during the prenecrotic phase of the cardiac condition, was fully effective in preventing myocardial overload as well as necrotization. These findings demonstrate that overload with calcium of cardiomyopathic cells of the hamsters can be influenced beneficially. Therefore, the disturbed myocardial calcium metabolism in the hereditary cardiomyopathy of the Syrian hamster is considered a decisive pathogenetic factor.