Prevention of hereditary cardiomyopathy in the syrian hamster with chronic verapamil therapy

• Published in: Journal of the American College of Cardiology 1988-12, Vol.12 (6), p.1599-1604
• Main Authors: Factor, Stephen M., Cho, Sangho, Scheuer, James, Sonnenblick, Edmund H., Malhotra, Ashwani
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - analysis; Animals; Biological and medical sciences; Cardiomyopathies - etiology; Cardiomyopathies - prevention & control; Cardiovascular system; Cricetinae; Medical sciences; Mesocricetus; Miscellaneous; Myosins - analysis; Pharmacology. Drug treatments; Spasm - complications; Verapamil - administration & dosage; Verapamil - therapeutic use
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(88)80031-7

The cardiomyopathic Syrian hamster develops genetically determined cardiac necrosis that invariably leads to premature death from congestive heart failure or arrhythmia. This hamster is a valuable model of human disease because it has many features in common with clinical dilated, congestive cardiomyopathy. Previous studies have shown that therapy for several weeks with the calcium channel blocking drug verapamil or the alpha-1 adrenoceptor blocking drug prazosin can prevent myocardial necrosis due to microvascular spasm. Other investigations have demonstrated the positive effects of verapamil in the early stages of disease. It is not clear, however, whether continued treatment can prevent the long-term expression of the cardiomyopathy or whether the disease is genetically predetermined. To address this question, hamsters were treated with oral verapamil for 7 to 8 months during the necrotizing, compensatory hypertrophy and early failure stages of disease. Analysis of myocardial pathologic and biochemical variables demonstrated that continuously treated animals were generally similar to unaffected control hamsters; discontinuous therapy led to partial protection. These findings demonstrate that virtually complete prevention of this hereditary disease is feasible; these results may have important implications for the treatment of human cardiomyopathy.