Cardiovascular Research Advance Access [Accepted Manuscript] published online on May 28, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp168
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Therapeutic effect of β-adrenoceptor blockers using a mouse model of dilated cardiomyopathy with a troponin mutation
1 Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
2 Department of Physiology and Biophysics and Center for Cardiovascular Research, University of Illinois at Chicago, College of Medicine, Chicago IL 60612, USA
3 Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Correspondence to: Sachio Morimoto, PhD Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, Tel: +81-92-642-6081, Fax: +81-92-642-6084, E-mail: morimoto{at}med.kyushu-u.ac.jp
Aims: Extensive clinical studies have demonstrated that β-adrenoceptor blocking agents (β-blockers) are beneficial in the treatment of chronic heart failure which is due to various etiologies, including idiopathic dilated cardiomyopathy (DCM) and ischemic heart disease. However, little is known about the therapeutic efficacy of β-blockers in the treatment of the inherited form of DCM, of which causative mutations have recently been identified in various genes, including those encoding cardiac sarcomeric proteins. Using a mouse model of inherited DCM with a troponin mutation, we aim to study the treatment benefits of β-blockers.
Methods: Three different types of β-blockers, carvedilol, metoprolol and atenolol, were orally administered to a knock-in mouse model of inherited DCM with a deletion mutation 
K210 in the cardiac troponin T gene (TNNT2). Therapeutic effects were examined based on survival and myocardial remodeling.
Results: The lipophilic β1-selective β-blocker metoprolol was found to prevent cardiac dysfunction and remodeling and extend survival of knock-in mice. Conversely, both the nonselective β-blocker carvedilol and the hydrophilic β1-selective β-blocker atenolol had no beneficial effects on survival and myocardial remodeling in this mouse model of inherited DCM.
Conclusion: The highly lipophilic β1-selective β-blocker metoprolol, known to prevent ventricular fibrillation via central nervous system-mediated vagal activation, may be especially beneficial to DCM patients showing a family history of frequent sudden cardiac death, such as those with a deletion mutation K210 in the TNNT2 gene.
KEYWORDS dilated cardiomyopathy; β–blocker; ventricular fibrillation; sudden death; survival
Time for primary review: 31 Days
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Cardiovasc Res 2009 84: 7-8.
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  R. Aguilar-Torres Found in translation: metoprolol improves survival more than carvedilol in a mouse model of inherited dilated cardiomyopathy Cardiovasc Res, October 1, 2009; 84(1): 7 - 8. [Full Text] [PDF]
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