Cardioprotection by oxyfedrine in hereditary cardiomyopathic hamsters

Abstract

A defect of the myocardial plasma membrane, resulting in increased transmembrahe calcium conductivity with consecutive myocardial calcium accumulation and exhaustion of high energy phosphates is considered the determinant factor for cardiac degeneration in the dystrophic cardiomyopathy of Syrian hamsters from strain BIO 8262. Since oxyfedrine (L-3-[[~-hydroxy-a-methyl-phenethylamino]-3'methoxy-propiophenone hydrochloride), a drug against coronary heart disease, is described as a partial [3-adrenoceptor agonist ir~ducing moderate stimulation of 6adrenoceptors and simultaneously exerting an unspecific quinidine-like membrane effect on cardiac and smooth muscle, itwas of interest to investigate the action of this substance on the development of the hereditary hamster cardiomyopathy.Although during the prenecrotic stage of the disease only a very high acute dose of oxyfedrine (60 mg/kg s.c.) was able to distinctly counteract myocardial calcium accumulation induced by isoproterenol (1 mg/kg s.c.), chronical administration of low doses of oxyfedrine (twice daily 0.3 mg/kg s.c.) -as applied in humans -were able to considerably suppress spontaneous myocardial calcium accumulation. By chronical subcutaneous injection of 30 mg/kg oxyfedrine twice daily it was possible to avoid spontaneous myocardial calcium accumulation as well as to nearly prevent degeneration of the myocardium.These findings suggest that oxyfedrine exerts cardioprotection by its calcium antagonistic properties.The aminoketone derivative oxyfedrine (L-3-[~-hydroxy-a-methylphenethylamino]-3'-methoxy-propiophenone hydrochloride) is clinically used as a drug against coronary heart disease (42,39,36,15,44,13,27). Pharmacologically it is described as a partial ~-adrenoceptor agonist inducing simultaneous stimulation of ~-adrenoceptors and blockade of catecholamines at adequate concentrations and a quinidine-like effect on cardiac and smooth muscle at higher concentrations (14,2,38,28, 11). Its ~adrenoceptor stimulatory effect, however, is about ten times lower than that of adrenaline (11). 833