Comparative Effects of Ca Slow Channel Blockers on the Hamster Hereditary Cardiomyopathy

Abstract

The use of Ca slow channel blockers for the prevention and treatment of ischemic heart diseases has received a wide acceptance in these recent years (1–4). In spite of their potential effectiveness to prevent Ca overload in reversibly injured myocardial cells (5,6), there is as yet little evidence that these slow channel blockers foster any therapeutic interest for the treatment of primary cardiomyopathies. The hamster hereditary cardiomyopathy includes several of the pathologic components which characterize spontaneously-occurring heart cell degeneration (7,8). The myocardial changes that progressively develop in these animals are an expression of a more generalized myopathic process which in all probability derives from an identical genetic molecular defect(s). Some ten years ago, we demonstrated that verapamil, one of the earliest Ca slow channel blockers, prevented the hamster hereditary cardiomyopathy without changing the overall course of the generalized polymyopathy that prevails in these animals (7,9). Until now, the effectiveness of verapamil in hindering the progression of skeletal muscle changes has remained unexplained except for the fact that presumably Ca slow channel blockers have no direct physiologic or pharmacologic effect on skeletal muscle fibers in higher vertebrates (10,11). Indeed therapeutic trials with prenylamine and verapamil were found unsuccessful in human muscular dystrophy (12,13).