Cardiovascular Research Advance Access first published online on May 28, 2009
This version [Corrected Proof] published online on June 17, 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, 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
* Corresponding author. Tel: +81 92 642 6081; fax: +81 92 642 6084. E-mail address: 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 aetiologies, including idiopathic dilated cardiomyopathy (DCM) and ischaemic 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 and results: 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 on the basis of survival and myocardial remodelling. The lipophilic β1-selective β-blocker metoprolol was found to prevent cardiac dysfunction and remodelling and extend the survival of knock-in mice. Conversely, both the non-selective β-blocker carvedilol and the hydrophilic β1-selective β-blocker atenolol had no beneficial effects on survival and myocardial remodelling 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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