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


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 Ca(2+) sensitivity. These alterations were normalized by exercise. Sarcoplasmic reticulum Ca(2+)-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.


CONCLUSIONS
This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca(2+) homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.
Aït Mou
Younss
Y
INSERM U637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, Montpellier, France.
Reboul
Cyril
C
Andre
Lucas
L
Lacampagne
Alain
A
Cazorla
Olivier
O
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling; D024722:Cardiac Myosins / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
C506948:Atp2a2 protein, rat; D009124:Muscle Proteins; D018994:Myosin Light Chains; C107184:myosin light chain 2; D024722:Cardiac Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases