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Cardiovascular Research Advance Access first published online on August 14, 2008
This version [Corrected Proof] published online on September 12, 2008

Cardiovascular Research, doi:10.1093/cvr/cvn229
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure

Younss Aït Mou1,2, Cyril Reboul3, Lucas Andre1,2, Alain Lacampagne1,2 and Olivier Cazorla1,2,*

1 INSERM U637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, Montpellier, France
2 Université Montpellier1, UFR de Médecine, F-34295 Montpellier, France
3 EA-4278, Université Avignon et des Pays de Vaucluse, UFR Sciences F-84000, Avignon, France

* Corresponding author. Tel: +33 467 41 52 42; fax: +33 467 41 52 42. E-mail address: olivier.cazorla{at}inserm.fr

Aims: The exercise-induced beneficial mechanisms after long-term myocardial infarction (MI) are incompletely understood. The present study evaluated the effect of treadmill exercise training (5 weeks), started at a late stage of heart failure (HF) (13 weeks post-MI), on rat left ventricle remodelling and dysfunction of the regional global and cellular contractile functions.

Methods and results: In vivo echocardiography confirmed that sub-endocardial (ENDO) layers contract more (+86%) and faster (+50%) than the sub-epicardial (EPI) layers. This gradient was lost in MI rats due to a predominant reduction in the ENDO layer contractility. Exercise partially restored the amplitude and velocity of ENDO contraction, resulting in a partial recovery of the pump function indexed by the aortic blood-flow velocity time integral. At the cellular level, MI impaired ENDO contractile properties by reducing cell shortening (10–7%), calcium transient, and myofilament Ca2+ sensitivity. These alterations were normalized by exercise. Sarcoplasmic reticulum Ca2+-ATPase (SERCA)2a expression and myosin light chain (MLC)-2 phosphorylation in ENDO cells were significantly reduced after MI and were restored by exercise. The EPI layer was only slightly reduced in vivo without cellular alterations.

Conclusion: This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca2+ homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.

KEYWORDS End-stage heart failure; Myocardial contractility; Contraction; Exercise; Myocardial infarction


Time for primary review: 27 days

This is a new version of this article as the first author's name was incorrect in the running header.


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