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The aim of the present study was to evaluate the Ca2+ handling and contractility properties of cardiomyocytes isolated from rats with high intrinsic aerobic exercise capacity. Standard-performance (SP) and high-performance (HP) rats were categorized with a treadmill progressive exercise test according to the exercise time to fatigue (TTF). The SP group included rats with TTF between 16.63 and 46.57 min, and the HP group included rats with TTF>46.57 min. Isolated ventricular cardiomyocytes were dissociated from the hearts of SP and HP rats, and intracellular global Ca2+ ([Ca2+]i) transients were measured. The [Ca2+]i transient peak was increased in the HP group relative to the SP group (5.54+/-0.31 vs. 4.18+/-0.12 F/F0; P

We tested the effects of low-intensity endurance training (LIET) on the structural and mechanical properties of right (RV) and left ventricular (LV) myocytes. Male Wistar rats (4 mo old) were randomly divided into control (C, n = 7) and trained (T, n = 7, treadmill running at 50-60% of maximal running speed for 8 wk) groups. Isolated ventricular myocyte dimensions, contractility, Ca(2+) transients {intracellular Ca(2+) concentration ([Ca(2+)]i)}, and ventricular [Ca(2+)]i regulatory proteins were measured. LIET augmented cell length (C, 152.5 ± 2.0 μm vs. T, 162.2 ± 2.1 μm; P < 0.05) and volume (C, 5,162 ± 131 μm(3) vs. T, 5,506 ± 132 μm(3); P < 0.05) in the LV but not in the RV. LIET increased cell shortening (C, 7.5 ± 0.3% vs. T, 8.6 ± 0.3%; P < 0.05), the [Ca(2+)]i transient amplitude (C, 2.49 ± 0.06 F/F0 vs. T, 2.82 ± 0.06 F/F0; P < 0.05), the expression of sarcoplasmic reticulum Ca(2+)-ATPase 2a (C, 1.07 ± 0.13 vs. T, 1.59 ± 0.12; P < 0.05), and the levels of phosphorylated phospholamban at serine 16 (C, 0.99 ± 0.11 vs. T, 1.34 ± 0.10; P < 0.05), and reduced the total phospholamban-to-sarcoplasmic reticulum Ca(2+)-ATPase 2a ratio (C, 1.19 ± 0.15 vs. T, 0.40 ± 0.16; P < 0.05) in the LV without changing such parameters in the RV. In conclusion, LIET affected the structure and improved the mechanical properties of LV but not of RV myocytes in rats, helping to characterize the functional and morphological changes that accompany the endurance training-induced cardiac remodeling.

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We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

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Background: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and β-adrenergic contractility in murine ventricular cardiomyocytes. Methods: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca²⁺sparks analysis. Results: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after β-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca²⁺sparks were observed in PRG cardiomyocytes. Conclusion: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the β-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca²⁺ intracellular kinetics.