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European Heart Journal Advance Access originally published online on September 1, 2005
European Heart Journal 2005 26(20):2193-2199; doi:10.1093/eurheartj/ehi478
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction

Paul Milliez1,2, Noeleen DeAngelis3, Catherine Rucker-Martin4, Antoine Leenhardt1,2, Eric Vicaut5, Estelle Robidel1, Philippe Beaufils2, Claude Delcayre1 and Stéphane N. Hatem6,7,*

1Centre de Recherches Cardiovasculaires Inserm Lariboisière—Unité U689, Paris, France
2Service de Cardiologie, Hôpital Lariboisière, Paris, France
3Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
4CNRS-UMR 8078, Hôpital Marie Lannelongue, Le Plessis Robinson, France
5Centre d'investigation clinique, Hôpital Lariboisière, Paris, France
6INSERM Unité 621, Faculté de Médecine Pitié Salpétrière, Université Pierre et Marie Curie, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France
7Centre d'Exploration Fonctionnelle Intégrée Faculté de Médecine Xavier Bichat, Paris, France

Received 12 February 2005; revised 22 July 2005; accepted 11 August 2005; online publish-ahead-of-print 1 September 2005.

* Corresponding author. Tel: +33 1 40 77 96 49; fax: +33 1 40 77 98 72. E-mail address: stephane.hatem{at}chups.jussieu.fr

See page 2079 for the editorial comment on this article (doi:10.1093/eurheartj/ehi477)

Aims Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling.

Methods and results Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography–Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8±0.6 mm in MI vs. 3.6±0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7±3.8% in MI vs. 10.5±2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration.

Conclusion Atrial fibrosis caused by chronic CHF is reduced by spironolactone.

Key Words: Heart failure • Fibrosis • Atrial myocardium • Spironolactone • Atrial fibrillation


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