Response To Exercise Research Articles

A novel method for determining ventilatory and gas exchange dynamics during exercise: the "chirp" waveform.

Quantitating exercise ventilatory and gas exchange dynamics affords insights into physiological control processes and cardiopulmonary dysfunction. We designed a novel waveform, the chirp waveform, to efficiently extract moderate-intensity exercise response dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively from ∼8.5 to 1.4 min over 30 min of cycle ergometry. We hypothesized that response dynamics of pulmonary ventilation (V̇e) and gas exchange [oxygen uptake (V̇o2) and carbon dioxide output (V̇co2)] extracted from chirp waveform are similar to those obtained from stepwise transitions. Thirty-one participants [14 young healthy, 7 older healthy, and 10 patients with chronic obstructive pulmonary disease (COPD)] exercised on three occasions. Participants first performed ramp-incremental exercise for gas exchange threshold (GET) determination. In randomized order, the next two visits involved either chirp or stepwise waveforms. Work rate amplitude (20 W to ∼95% GET work rate) and exercise duration (30 min) were the same for both waveforms. A first-order linear transfer function with a single system gain (G) and time constant (τ) characterized response dynamics. Agreement between model parameters extracted from chirp and stepwise waveforms was established using Bland-Altman analysis and Rothery's concordance coefficient (RCC). V̇e, V̇o2, and V̇co2 Gs showed no systematic bias (P > 0.178) and moderate-to-good agreement (RCC > 0.772, P < 0.01) between waveforms. Similarly, no systematic bias (P = 0.815) and good agreement (RCC = 0.837, P < 0.001) was found for τV̇o2. Despite moderate agreement for τV̇co2 (RCC = 0.794, P < 0.001) and τV̇e (RCC = 0.722, P = 0.083), chirp τ was less [-6.9(11.7) s and -12.2(22.5) s, respectively]. We conclude that the chirp waveform is a promising method for measuring exercise response dynamics and investigating physiological control mechanisms.NEW & NOTEWORTHY We investigated the ability of a novel waveform to extract exercise ventilatory and gas exchange dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively over 30 min of exercise. In a study of 31 healthy individuals and patients with COPD, comparison of exercise dynamics derived from chirp to those from stepwise waveforms suggests that the chirp waveform is a promising method for derivation of exercise response dynamics.

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p&amp;lt;0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p&amp;lt;0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

A replicate crossover trial on the inter-individual variability of sleep indices in response to acute exercise undertaken by healthy men.

Using the necessary replicate-crossover design, we investigated whether there is inter-individual variability in home-assessed sleep in response to acute exercise. Eighteen healthy men (mean(SD): 26(6) years) completed two identical control (8-h laboratory rest, 08:45-16:45) and two identical exercise (7-h laboratory rest; 1-h laboratory treadmill run [62(7)% peak oxygen uptake], 15:15-16:15) trials in randomised sequences. Wrist-worn actigraphy (MotionWatch 8) measured home-based sleep (total sleep time, actual wake time, sleep latency, sleep efficiency) two nights before (nights 1-2) and three nights after (nights 3-5) the exercise/control day. Pearson's correlation coefficients quantified the consistency of individual differences between the replicates of control-adjusted exercise responses to explore: (1) immediate (night 3 minus night 2); (2) delayed (night 5 minus night 2); and (3) overall (average post-intervention minus average pre-intervention) exercise-related effects. Within-participant linear mixed models and a random-effects between-participant meta-analysis estimated participant-by-trial response heterogeneity. For all comparisons and sleep outcomes, the between-replicate correlations were non-significant, ranging from trivial-to-moderate (r range = -0.44 to 0.41, P≥0.065). Participant-by-trial interactions were trivial. Individual differences SDs were small, prone to uncertainty around the estimates indicated by wide 95% confidence intervals and did not provide support for true individual response heterogeneity. Meta-analyses of the between-participant, replicate-averaged condition effect revealed that, again, heterogeneity (τ) was negligible for most sleep outcomes. Control-adjusted sleep in response to acute exercise was inconsistent when measured on repeated occasions. Inter-individual differences in sleep in response to exercise were small compared to the natural (trial-to-trial) within-subject variability in sleep outcomes.

Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.

Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Here, we test the hypothesis that loss of PKP2 expression leads to pro-arrhythmic changes in atrial cardiomyocytes. Atrial cells/tissue were obtained from a cardiac-specific, tamoxifen-activated model of PKP2 deficiency (PKP2cKO). By contrast to PKP2cKO ventricular myocytes, PKP2cKO atrial cardiomyocytes presented no significant differences in intracellular calcium (Ca2+ i) transient dynamics, sarcoplasmic reticulum load or action potential morphology. PKP2cKO atrial cardiomyocytes showed elevated reactive oxygen species levels, increased frequency and amplitude of Ca2+ sparks, and increased diastolic [Ca2+]i compared to control; the latter two parameters were further increased by isoproterenol exposure and reversed by exposure to ryanodine receptor blocker dantrolene. We speculate that these isoproterenol-dependent effects may impact on the exercise-related atrial arrhythmia risk in ARVC patients. Despite absence of changes in Ca2+ i transient dynamics, PKP2cKO atrial cardiomyocytes showed enhanced sarcomere shortening and impaired sarcomere relaxation. Orthogonal transcriptomic analysis of human(GTEx) and PKP2cKO atrial tissue led to identification of 41 transcripts depending on PKP2 expression. Biochemical follow-up confirmed reduced abundance of sarcomeric protein myosin binding protein C, potentially playing a role in cellular shortening and relaxation changes observed. Our findings provide novel insights into the role of PKP2 in atrial myocardium with potential implications to therapeutic management of atrial fibrillation in patients with PKP2-related ARVC. KEY POINTS: Atrial arrhythmias occur in a large group of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a cardiac disease mostly caused by pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Exercise is considered to be an independent risk factor for arrhythmias consequent to PKP2 deficiency. Weshow that loss of PKP2 expression affects cellular calcium handling and electrophysiology differently in left atrial vs. ventricular myocardium and causes extensive atrial fibrosis. PKP2-deficient atrial cardiomyocytes present increased spontaneous sarcoplasmic reticulum calcium release events, furtherenhancedby isoproterenol exposure and reversiblebya ryanodine receptor blocker(dantrolene). In addition, PKP2-deficient atrial myocytes exhibit impaired relaxation and enhanced sarcomere shortening, most probably related to reduced abundance of myosin binding protein C. We speculate that cellular effects reported upon isoproterenol impact on the exercise-related atrial arrhythmia risk in ARVC patients. We further propose that therapeutic approaches aimed at mitigating ventricular damage may be effective to treat the atrial disease in ARVC.

Impairment of Cardiovascular Functional Capacity in Mild to Moderate Kidney Dysfunction.

Traditional diagnostic tools that assess resting cardiac function and structure fail to accurately reflect cardiovascular alterations in patients with chronic kidney disease (CKD). This study sought to determine whether multidimensional exercise response patterns related to cardiovascular functional capacity can detect abnormalities in mild-to-moderate CKD. In a cross-sectional study, we examined 3,075 participants from the Framingham Heart Study (FHS) and 451 participants from the Massachusetts General Hospital Exercise Study (MGH-ExS) who underwent cardiopulmonary exercise testing (CPET). Participants were stratified by estimated glomerular filtration rate (eGFR): eGFR ≥90; eGFR 60-89; eGFR 30-59. Our primary outcomes of interest were peak oxygen uptake (VO 2 Peak),VO 2 at anaerobic threshold (VO 2 AT), and the ratio of minute ventilation to carbon dioxide production (VE/VCO 2 ). Multiple linear regression models were fitted to evaluate the associations between eGFR group and each outcome variable adjusted for covariates. In the FHS cohort, N=1,712 (56%) had an eGFR ≥90 ml/min/1.73m 2 , N=1,271 (41%) had an eGFR 60-89 ml/min/1.73m 2 , and N=92 (3%) had an eGFR 30-59 ml/min/1.73m 2 . In the MGH-ExS cohort, N=247 (55%) had an eGFR ≥90 ml/min/1.73m 2 , N=154 (34%) had an eGFR 60-89 ml/min/1.73m 2 , and N=50 (11%) had an eGFR 30-59 ml/min/1.73m 2 . In FHS, VO 2 Peak and VO 2 AT were incrementally impaired with declining kidney function ( p <0.001); however this pattern was attenuated following adjustment for age. Percent-predicted VO 2 Peak at AT was higher in the lower eGFR groups ( p <0.001). In MGH-ExS, VO 2 Peak and VO 2 AT were incrementally impaired with declining kidney function in unadjusted and adjusted models ( p <0.05). VO 2 Peak was associated with eGFR ( p <0.05) in all models even after adjusting for age. On further mechanistic analysis, we directly measured cardiac output (CO) at peak exercise via right heart catheterization and found impaired CO in the lower eGFR groups ( p ≤0.007). CPET-derived indices may detect impairment in cardiovascular functional capacity and track cardiac output declines in mild to moderate CKD.

Acute endothelial, blood pressure, and glycemic responses after aerobic sessions in type-2 diabetic with hypertension: A double-blinded randomized study

ObjectivesTo compare the acute response of moderate intensity continuous exercise (MICE) vs moderate intensity interval exercise (MIIE) on endothelial function, post-exercise hypotension (PEH), and glycemia in type 2 diabetes (T2DM) with hypertension. MethodsTwelve T2DM (aged 52.8±3.8 years old) patients with hypertension underwent a randomized cross-over study following isocaloric (200 kcal) protocols: (i) MICE: walk-jogging at 50% of VO2peak, (ii) MIIE session: walking – jogging (stimulus/recovery – 3:3 minutes each) at 60% of VO2peak followed by recovery at 40% of VO2peak, and (iii) control (CON): lying quietly in a supine position for 30 minutes. A generalized estimating equation was utilized to verify possible differences over time × session. ResultsThe %FMD (Baseline: 3.59±1.58 vs. 30 min: 6.73±4.34) and the absolute FMD changed after MIIE (Baseline: 0.16±0.10 vs. 30 min: 0.17±0.14). Only absolute FMD changed after MIIE (Baseline: 0.14±0.07 vs. 30 min: 0.16±0.07). Besides, MIIE at 30 minutes provides higher absolute FMD values when compared to baseline from MICE and baseline, 30 minutes, and 60 minutes from control. Regarding blood pressure, no PEH statistical main effect was found. Finally, the glycemia changed at baseline vs. 30 minutes and 60 minutes after MIIE (210.5±9.4 vs. 127.6±10.0 and 120±8.9), MICE (219.5±12.7 vs. 125.2±12.0 and 118.2±11.6), and control sessions (215.9±11.8 vs. 187.4±11.2 and 172.6±11.3 mg/dL, p<0.05). However, MIIE and MICE showed higher decreases compared to the control. ConclusionsMIIE and MICE sessions are similar and effective exercise strategies to induce changes in endothelial function and glycemic responses in type-2 diabetics with hypertension.

Heart Rate Response In Maximal Exercise Is Related With Coronary Heart Disease

Heart Rate Response In Maximal Exercise Is Related With Coronary Heart Disease

Exercise And Lymphocyte Activation Responses In Patients With Post-covid-19 Syndrome: An Exploratory Analysis From “Exer-covid” Trial

Exercise And Lymphocyte Activation Responses In Patients With Post-covid-19 Syndrome: An Exploratory Analysis From “Exer-covid” Trial

Exercise-induced adaptations to homeostasis of reactive oxygen species in skeletal muscle.

Reactive oxygen species are generated by multiple mechanisms during contractile activity in exercising skeletal muscle and are recognised to play a role in signaling adaptations to the contractions. The sources of the superoxide and hydrogen peroxide generated are now relatively well understood but how the resulting low concentrations of hydrogen peroxide induce activation of multiple signaling pathways remains obscure. Several theories are presented together with accumulating evidence that 2-Cys peroxiredoxins may play a role of "effector" proteins in mediating the signaling actions of hydrogen peroxide. Identification of the mechanisms underlying these pathways offers the potential in the longer term for development of novel interventions to maintain exercise responses in the elderly with the potential to maintain muscle mass and function and consequent quality of life.

Application of Multispectral Optoacoustic Tomography for Lower Limb Musculoskeletal Sports Injuries in Adults

Compositional changes in relation to musculoskeletal injuries are difficult to measure non-invasively. This study aims to use non-invasive label-free imaging with Multispectral Optoacoustic Tomography (MSOT) to evaluate compositional changes with injury.Five different patient groups were examined, covering diagnoses of Achilles or patellar tendinopathy, Achilles tendon rupture and gastrocnemius muscle strain injury. Injured and contralateral limbs were imaged using a commercial MSOT device. Hemoglobin, collagen, and lipid contents were estimated. Some patients were examined before and after exercise.Hemoglobin measures had high reproducibility and displayed systematic changes in response to exercise. The content and exercise response of hemoglobin was equal on both limbs. In contrast, collagen and lipid measures were inconsistent and did not display the expected distribution.In conclusion, MSOT is applicable to imaging of hemoglobin in musculoskeletal injuries, providing complimentary information to conventional ultrasound, but applicability to other components like collagen and lipids could not be shown.

Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p

Regular physical activity is widely recognized for reducing the risk of various disorders, with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues. However, many individuals, particularly the elderly and those with clinical conditions, are unable to engage in physical exercise, necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules. Histone acetylation and deacetylation significantly influence exercise-induced gene expression, suggesting that targeting histone deacetylases (HDACs) could mimic some exercise responses. In this study, we explored the effects of the HDAC inhibitor Trichostatin A (TSA) on human skeletal muscle myoblasts (HSMMs). Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles (EVs) enriched with miR-873-3p. These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) by targeting H2 calponin (CNN2). In vivo, systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass. Moreover, TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs, suggesting that HDAC inhibition can replicate exercise-induced bone health benefits. These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis, particularly for individuals unable to exercise. Given the FDA-approved status of various HDAC inhibitors, this approach holds significant promise for rapid clinical translation in osteoporosis treatment.

GEPREP: A comprehensive data atlas of RNA-seq-based gene expression profiles of exercise responses

BackgroundPhysical activity can regulate and affect gene expression in multiple tissues and cells. Recently, with the development of next-generation sequencing, a large number of RNA-sequencing (RNA-seq)-based gene expression profiles about physical activity have been shared in public resources; however, they are poorly curated and underutilized. To tackle this problem, we developed a data atlas of such data through comprehensive data collection, curation, and organization. MethodsThe data atlas, termed gene expression profiles of RNA-seq-based exercise responses (GEPREP), was built on a comprehensive collection of high-quality RNA-seq data on exercise responses. The metadata of each sample were manually curated. Data were uniformly processed and batch effects corrected. All the information was well organized in an easy-to-use website for free search, visualization, and download. ResultsGEPREP now includes 69 RNA-seq datasets of pre- and post-exercise, comprising 26 human datasets (1120 samples) and 43 mouse datasets (1006 samples). Specifically, there were 977 (87.2 %) human samples of skeletal muscle and 143 (12.8 %) human samples of blood. There were also samples across 9 mice tissues with skeletal muscle (359, 35.7 %) and brain (280, 27.8 %) accounting for the main fractions. Metadata—including subject, exercise interventions, sampling sites, and post-processing methods—are also included. The metadata and gene expression profiles are freely accessible at http://www.geprep.org.cn/. ConclusionGEPREP is a comprehensive data atlas of RNA-seq-based gene expression profiles responding to exercise. With its reliable annotations and user-friendly interfaces, it has the potential to deepen our understanding of exercise physiology.

Effects of preterm birth on the pattern of altitude acclimatization at rest and during moderate-intensity exercise across three days at 3,375 m.

Preterm birth elicits long-lasting physiological effects in various organ systems, potentially modulating exercise and environmental stress responses. To establish whether prematurely-born adults respond uniquely during early high-altitude acclimatization at rest and during exercise, 17 healthy adults born preterm (gestational age < 32 wk) and 17 term-born, age- and aerobic-capacity-matched, control participants completed a three-day high-altitude sojourn (3,375 m). Oxygen uptake, pulmonary ventilation, and hemodynamic responses, as well as pulse oxygen saturation, brain tissue saturation index (TSI), and skeletal muscle TSI, were measured daily at rest and during moderate-intensity steady-state exercise bouts. In general, the prematurely-born group displayed comparable acclimatization responses at rest, with similar ventilation and cardiac output observed between groups throughout. Resting brain TSI was, however, higher in the preterm group upon arrival at high altitude (72 ± 7% vs. 68 ± 3%; d = 1.20). Absolute exercising oxygen uptake was lower in the preterm participants (P = 0.047), with this group displaying lower exercising cardiac output underpinned by reduced stroke volume (both P = 0.035). Nevertheless, exercising minute ventilation (V̇e) did not differ between groups (P = 0.237) while brain TSI (70 ± 6% vs. 66 ± 3%; d = 1.35) and pulse oxygen saturation (85 ± 3% vs. 82 ± 5%; d = 1.52) were higher with prematurity upon arrival to high altitude. These findings suggest that healthy prematurely-born adults exhibit comparable early acclimatization patterns to their term-born counterparts and better maintain cerebral oxygenation at rest. Together, these data suggest that prematurely-born adults should not be discouraged from high-altitude sojourns involving physical activity.NEW & NOTEWORTHY The acclimatization pattern across three days at 3,375 m, at rest and during moderate-intensity exercise, was similar between healthy adults born prematurely and their term-born counterparts. Preterm adults free from respiratory complications were found to better maintain brain tissue and capillary oxygen saturation at high altitudes, whereas the term-born group experienced larger altitude-induced reductions. Despite apparent cardiac limitations, preterm individuals tolerated exercise similarly to their term-born peers. These findings underscore the notion that preterm birth per se does not predispose healthy adults to decreased altitude tolerance during exercise.

Differential response to preoperative exercise training in patients candidates to cardiac valve replacement

BackgroundThere is lack of evidence regarding safety, effectiveness and applicability of prehabilitation on cardiac surgery population, particularly in patients candidates to cardiac valve replacement. The aim of the study is to assess and compare the effect of a multimodal prehabilitation program on functional capacity in patients with severe aortic stenosis (AoS) and severe mitral regurgitation (MR) proposed for valve replacement surgery.MethodsSecondary analysis from a randomised controlled trial whose main objective was to analyze the efficacy of a 4–6 weeks multimodal prehabilitation program in cardiac surgery on reducing postoperative complications. For this secondary analysis, only candidates for valve replacement surgery were selected. The primary outcome was the change in endurance time (ET) from baseline to preoperative assessment measured by a cycling constant work-rate cardiopulmonary exercise test.Results68 patients were included in this secondary analysis, 34 (20 AoS and 14 MR) were allocated to the prehabilitation group and 34 (20 AoS and 14 MR) to control group. At baseline, patients with AoS had better left systolic ventricular function and lower prevalence of atrial fibrillation compared to MR (p = 0.022 and p = 0.035 respectively). After prehabilitation program, patients with MR showed greater improvement in ET than AoS patients (101% vs. 66% increase from baseline). No adverse events related to the prehabilitation program were observed.ConclusionsA 4–6 week exercise training program is safe and overall improves functional capacity in patients with severe AoS and MR. However, exercise response is different according to the cardiac valve type disfunction, and further studies are needed to know the factors that predispose some patients to have better training response.Trial registrationThe study has been registered on the Registry of National Institutes of Health ClinicalTrials.gov (NCT03466606) (05/03/2018).

Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a post-transcriptional influence.

Exercise plays a crucial role in promoting muscle health, but our understanding of nuclear proteins orchestrating exercise responses is limited. Isolation of skeletal muscle nuclei coupled with mass spectrometry enhanced the identification of nuclear proteins. This approach was used to investigate the effects of acute exercise, revealing changes in the muscle nuclear proteome 1-hour post-exercise, including proteins linked to post-transcriptional processing and splicing. Our findings offer insights into the exercise-induced changes within muscle nuclear proteins.

The cardiovascular exercise response in children with overweight or obesity measured by cardiovascular magnetic resonance imaging.

Overweight and obesity are among the main causes of cardiovascular diseases. Exercise testing can aid in the early detection of subtle cardiac dysfunction not present in rest. We hypothesized that the cardiovascular response to exercise is impaired among children with overweight or obesity, characterized by the inability of the cardiovascular system to adapt to exercise by increasing cardiac volumes and blood pressure. We performed a cardiovascular stress test to investigate whether the cardiovascular exercise response is altered in children with overweight and obesity, as compared to children with a normal weight. A subgroup of the Generation R population-based prospective cohort study, consisting of 41 children with overweight or obesity and 166 children with a normal weight with a mean age of 16 years, performed an isometric exercise. Continuous heart rate and blood pressure were measured during rest, exercise and recovery. Cardiovascular magnetic resonance (CMR) measurements were performed during rest and exercise. Higher BMI was associated with a higher resting systolic and diastolic blood pressure (difference: 0.24 SDS (95% CI 0.10, 0.37) and 0.20 SDS (95% CI 0.06, 0.33)) and lower systolic and diastolic blood pressure increases from rest to peak exercise (-0.11 SDS (95% CI -0.20, -0.03) and -0.07 SDS (95% CI -0.07, -0.01)). BMI was also associated with a slower decrease in systolic and diastolic blood pressure during recovery (p values < 0.05). Higher childhood BMI was associated with lower BSA corrected left ventricular mass, end-diastolic volume and stroke volume (p values < 0.05). There were no associations of childhood BMI with the cardiac response to exercise measured by heart rate and CMR measurements. Childhood BMI is, across the full range, associated with a blunted blood pressure response to static exercise but there were no differences in cardiac response to exercise. Our findings suggest that adiposity may especially affect the vascular exercise reaction without affecting cardiac response.

Exercise responses to repeated cycle sprints with continuous and intermittent hypoxic exposure.

We examine the impact of the acute manipulation of oxygen availability during discrete phases (active and passive) of a repeated-sprint cycling protocol on performance, physiological, and perceptual responses. On separate days, twelve trained males completed four sets of five 5-s 'all out' cycle sprints (25-s inter-sprint recovery and 5-min interset rest) in four randomized conditions: normobaric hypoxia (inspired oxygen fraction of 12.9%) applied continuously (C-HYP), intermittently during only the sets of sprints (I-HYPSPRINT) or between-sets recovery periods (I-HYPRECOVERY), or not at all (C-NOR). Peak and mean power output, peripheral oxygen saturation, heart rate, blood lactate concentration, exercise-related sensations, and vastus lateralis muscle oxygenation using near-infrared spectroscopy were assessed. Peak and mean power output was ∼4%-5% lower for C-HYP compared to C-NOR (P≤0.050) and I-HYPRECOVERY (P≤0.027). Peripheral oxygen saturation was lower during C-HYP and I-HYPSPRINT compared with C-NOR and I-HYPRECOVERY during sets of sprints (∼83-85 vs. ∼95%-97%; P<0.001), while lower values were obtained for C-HYP and I-HYPRECOVERY than C-NOR and I-HYPSPRINT during between-sets rest period (∼84-85 vs. ∼96%; P<0.001). Difficulty in breathing was ∼21% higher for C-HYP than C-NOR (P=0.050). Ratings of perceived exertion (P=0.435), limb discomfort (P=0.416), heart rate (P=0.605), blood lactate concentration (P=0.976), and muscle oxygenation-derived variables (P=0.056 to 0.605) did not differ between conditions. In conclusion, the method of hypoxic exposure application (continuous vs. intermittent) affects mechanical performance, while internal demands remained essentially comparable during repeated cycle sprints.

Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.

Limb-Girdle Muscular Dystrophy R1/2A (LGMD R1/2A) is caused by mutations in the CAPN3 gene encoding Calpain 3, a skeletal-muscle specific, Ca2+-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca2+ homeostasis. Through live-cell Ca2+ measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in Capn3 deficient (C3KO) and wild-type (WT) mice, we determined whether loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca2+ influx measurements revealed loss of Capn3 elicits elevated resting SOCE and increased resting cytosolic Ca2+, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bout of treadmill running to elicit SOCE. Within 1HR post-treadmill running, C3KO mice exhibited diminished force production in extensor digitorum longus muscles and a greater decay of Ca2+ transients in flexor digitorum brevis muscle fibers during repetitive stimulation. Striking evidence for impaired exercise-induced SOCE activation in C3KO mice included poor colocalization of key SOCE proteins, stromal-interacting molecule 1 (STIM1) and ORAI1, combined with disappearance of CEUs in C3KO muscles. These results demonstrate that Calpain 3 is a key regulator of SOCE in skeletal muscle and identify SOCE dysregulation as a contributing factor to LGMD R1/2A pathology.

Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease.

Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD. We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise. Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured. Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen's d = 0.56). Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

Fat loss and muscle gain: The possible role of striatal dopaminergic tone in determining the efficacy of physical exercise

The effectiveness of exercise for obesity is contentious due to individual response variability. Owing to the roles of dopamine in motor functions, metabolism, and appetite, this study aimed to identify striatal dopamine as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. Healthy non-exercising males completed an 8-week program, exercising 1 h, 4 days a week. Striatal dopaminergic tone was assessed by measuring dopamine transporter availability using technetium-99 m labelled tropane derivative, [99mTc]TRODAT-1 (TRODAT), single-photon emission computed tomography, and body composition (fat and muscles mass) was analysed using bioelectrical impedance. Lower baseline dopamine levels were associated with greater fat mass loss (r = 0.58, p = 0.006), percentage fat mass loss (r = 0.53, p = 0.013), and increase in muscle mass (β = -0.53, p = 0.035, after taking age and smoking status as covariates). These findings enhance our understanding of obesity neurobiology and exercise response variability, necessitating further research for targeted interventions based on dopaminergic profiles.