Differences in Cardioprotective Efficacy of Adrenergic Receptor Antagonists and Ca2+ Channel Antagonists in an Animal Model of Dilated Cardiomyopathy: Effects on Gross Morphology, Global Cardiac Function, and Twitch Force

• Published in: Circulation research 1993-12, Vol.73 (6), p.1077-1089
• Main Authors: Glass, Mark G, Fuleihan, Farid, Liao, Ronglih, Lincoff, A Michael, Chapados, Rene, Hamlin, Robert, Apstein, Carl S, Allen, Paul D, Ingwall, Joanne S, Hajjar, Roger J, Cory, C Robert, OʼBrien, Peter J, Gwathmey, Judith K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiomyopathy, Dilated - chemically induced; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - physiopathology; Cardiovascular system; Furazolidone; Heart - drug effects; Heart - physiopathology; Heart Rate - drug effects; In Vitro Techniques; Medical sciences; Miscellaneous; Myocardial Contraction; Myocardium - pathology; Pharmacology. Drug treatments; Sympatholytics - pharmacology; Turkeys
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.73.6.1077

Turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (Fz-DCM). We tested whether five cardioactive agents were cardioprotective in this model of heart failure, ie, whether they prevented dilatation and wall thinning and improved contractile performance. We compared the effects of chronic administration of a β1-selective and a nonselective β-receptor antagonist, an β-receptor antagonist, and two Ca channel antagonists in the presence of Fz administration. The greatest cardioprotection was found with treatment with either propranolol or nifedipine. At the gross morphological level, the effect of propranolol (a nonselective β-adrenergic antagonist) was greater than the effect of atenolol (a selective β1-adrenergic antagonist), and the effect of nifedipine was greater than that of verapamil (Ca channel antagonists), with all agents more cardioprotective than phenoxybenzamine (an βl-adrenergic>β2-adrenergic antagonist). Differences in cardioprotective efficacy of each agent increased with increased concentration. These data indicate that the dose and choice of a specific type of Ca channel antagonist or β-receptor antagonist might be important in the treatment of dilated cardiomyopathy. All agents that were cardioprotective caused similar functional improvements at both the whole heart and isolated muscle levels. Compared with control animals, Fz-DCM animals showed a significant reduction in peak left ventricular (LV) developed pressure (92±17 versus 143±24 mm Hg, P