Interval training normalizes cCardiomyocyte function, diastolic Ca²⁺ control, and SR Ca²⁺ release synchronicity in a mouse model of diabetic cardiomyopathy

In the present study we explored the mechanisms behind excitation-contraction (EC)-coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db), and determined whether 13-weeks of aerobic interval training could restore cardiomyocyte Ca2+ cycling and EC-coupling. Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca2+ leak, reduced synchrony of Ca2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca2+ and caffeine-induced Ca2+ release. Additionally, the rate of SR Ca2+ ATPase (SERCA2a)-mediated Ca2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca2+ release indicated increased Na+/Ca2+- exchanger (NCX) activity. The increased SR-Ca2+ leak was attributed to increased Ca2+-calmodulindependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca2+ leak upon inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca2+ release synchronicity, T-tubule density, twitch Ca2+ amplitude, SERCA2a and NCX activities, and SR-Ca2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A (PKA) inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca2+ load when compared with the sedentary db/db mice. EC-coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition. These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type (WT)

Spin-State Transition and Metal-Insulator Transition in La1−x_{1-x}Eux_xCoO3_3}

We present a study of the structure, the electric resistivity, the magnetic susceptibility, and the thermal expansion of La$_{1-x}$Eu$_x$CoO$_3$. LaCoO$_3$ shows a temperature-induced spin-state transition around 100 K and a metal-insulator transition around 500 K. Partial substitution of La$^{3+}$ by the smaller Eu$^{3+}$ causes chemical pressure and leads to a drastic increase of the spin gap from about 190 K in LaCoO$_3$ to about 2000 K in EuCoO$_3$, so that the spin-state transition is shifted to much higher temperatures. A combined analysis of thermal expansion and susceptibility gives evidence that the spin-state transition has to be attributed to a population of an intermediate-spin state with orbital order for $x<0.5$ and without orbital order for larger $x$. In contrast to the spin-state transition, the metal-insulator transition is shifted only moderately to higher temperatures with increasing Eu content, showing that the metal-insulator transition occurs independently from the spin-state distribution of the Co$^{3+}$ ions. Around the metal-insulator transition the magnetic susceptibility shows a similar increase for all $x$ and approaches a doping-independent value around 1000 K indicating that well above the metal-insulator transition the same spin state is approached for all $x$.Comment: 10 pages, 6 figure

Evidence for a Low-Spin to Intermediate-Spin State Transition in LaCoO3

We present measurements of the magnetic susceptibility and of the thermal expansion of a LaCoO$_3$ single crystal. Both quantities show a strongly anomalous temperature dependence. Our data are consistently described in terms of a spin-state transition of the Co$^{3+}$ ions with increasing temperature from a low-spin ground state to an intermediate-spin state without (100K - 500K) and with (>500K) orbital degeneracy. We attribute the lack of orbital degeneracy up to 500K to (probably local) Jahn-Teller distortions of the CoO$_6$ octahedra. A strong reduction or disappearance of the Jahn-Teller distortions seems to arise from the insulator-to-metal transition around 500 K.Comment: an error in the scaling factor of Eq.(4) and consequently 2 values of table I have been corrected. The conclusions of the paper remain unchanged. See also: C. Zobel et al. Phys. Rev. B 71, 019902 (2005) and J. Baier et al. Phys. Rev. B 71, 014443 (2005

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

The effects of a 6-week strength training on critical velocity, anaerobic running distance, 30-m sprint and yo-yo intermittent running test performances in male soccer players

The objectives of this study were to examine the effects of a moderate intensity strength training on changes in critical velocity (CV), anaerobic running distance (D'), sprint performance and Yo-Yo intermittent running test (Yo-Yo IR1) performances. Methods: two recreational soccer teams were divided in a soccer training only group (SO; n = 13) and a strength and soccer training group (ST; n = 13). Both groups were tested for values of CV, D', Yo-Yo IR1 distance and 30-m sprint time on two separate occasions (pre and post intervention). The ST group performed a concurrent 6-week upper and lower body strength and soccer training, whilst the SO group performed a soccer only training. Results: after the re-test of all variables, the ST demonstrated significant improvements for both, YoYo IR1 distance (p = 0.002) and CV values (p<0.001) with no significant changes in the SO group. 30-m sprint performance were slightly improved in the ST group with significantly decreased performance times identified in the SO group (p<0.001). Values for D' were slightly reduced in both groups (ST -44.5 m, 95% CI = -90.6 to 1.6; SO -42.6 m, 95% CI = -88.7 to 3.5). Conclusions: combining a 6-week moderate strength training with soccer training significantly improves CV, Yo-Yo IR1 whilst moderately improving 30-m sprint performances in non-previously resistance trained male soccer players. Critical Velocity can be recommended to coaches as an additional valid testing tool in soccer

Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training

Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca2+ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca2+ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature