title: Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster.
abstract: The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.
authors: Department of Pathology, New York Medical College, Valhalla 10595.
authors: J M
authors: JM
authors: Capasso
authors: E H
authors: EH
authors: Sonnenblick
authors: P
authors: P
authors: Anversa
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000188:drug therapy / Q000503:physiopathology*; D006224:Cricetinae; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000517:prevention & control*; D008564:Membrane Potentials; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000503:physiopathology; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil