title: Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction.
abstract: The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca(2+)-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8+/-1 to 12+/-1%, and LVdP/dt(P30) from 5295+/-207 to 5794+/-207 mm Hg/s (both P<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca(2+)-sensitivity (DeltapCa(50)=0.037). This effect of exercise was PKA-mediated and likely because of improved beta(1)-adrenergic signaling, as suggested by the increased beta(1)-adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (F(max) increased from 14.3+/-0.7 to 18.3+/-0.8 kN/m(2) P<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1+/-0.3 to 7.0+/-0.6%; P<0.05). Furthermore, exercise reduced diastolic Ca(2+)-concentrations (by approximately 30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca(2+)-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.
authors.affiliation: Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Monique C
authors.initials: MC
authors.lastname: de Waard
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.forename: Virginie
authors.initials: V
authors.lastname: Bito
authors.forename: Semir
authors.initials: S
authors.lastname: Ozdemir
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Biesmans
authors.forename: Nicky M
authors.initials: NM
authors.lastname: Boontje
authors.forename: Dick H W
authors.initials: DH
authors.lastname: Dekkers
authors.forename: Kees
authors.initials: K
authors.lastname: Schoonderwoerd
authors.forename: Hans C H
authors.initials: HC
authors.lastname: Schuurbiers
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Stienen
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
authors.forename: Jos M J
authors.initials: JM
authors.lastname: Lamers
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010539:Permeability; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D011506:Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D011506:Proteins; D000242:Cyclic AMP