Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction
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-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/dtP30 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-sensitivity (ΔpCa50=0.037). This effect of exercise was PKA-mediated and likely because of improved β1-adrenergic signaling, as suggested by the increased β1-adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (Fmax increased from 14.3±0.7 to 18.3±0.8 kN/mP<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-concentrations (by ∼30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca-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.
|Keywords||Cardiac function, Cardiomyocytes, Exercise training, Heart failure|
|Persistent URL||dx.doi.org/10.1161/01.RES.0000262655.16373.37, hdl.handle.net/1765/32753|
|Note||Free full text at PubMed|
de Waard, M.C, van der Velden, J, Bito, V, Ozdemir, S, Biesmans, L, Boontje, N.M, … Duncker, D.J.G.M. (2007). Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction. Circulation Research, 100(7), 1079–1088. doi:10.1161/01.RES.0000262655.16373.37