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European Heart Journal Advance Access published online on September 1, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi478
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received February 12, 2005
Revised July 22, 2005
Accepted August 11, 2005

Preclinical research

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

Paul Milliez 1, Noeleen DeAngelis 2, Catherine Rucker-Martin 3, Antoine Leenhardt 1, Eric Vicaut 4, Estelle Robidel 5, Philippe Beaufils 6, Claude Delcayre 5, and Stéphane N. Hatem 7*

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

* To whom correspondence should be addressed.
Stéphane N. Hatem, E-mail: stephane.hatem{at}chups.jussieu.fr


  Abstract

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.

Keywords: Heart failure; Fibrosis; Atrial myocardium; Spironolactone; Atrial fibrillation.
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