Reduced Muscle Endurance Research Articles

Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.

It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised, and their cognitive function is impaired. EC-Tert-KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that Tert-KO EC have reduced mitochondrial content and function, which results in increased dependence on glycolysis. Consistent with this, EC-Tert-KO mice have metabolism changes indicative of increased glucose utilization. In EC-Tert-KO mice, expedited telomere attrition is observed for EC of adipose tissue (AT), while brain and skeletal muscle EC have normal telomere length but still display features of senescence. Our data indicate that the loss of Tert causes EC senescence in part through a telomere length-independent mechanism undermining mitochondrial function. We conclude that EC-Tert-KO mice is a model of expedited vascular senescence recapitulating the hallmarks aging, which can be useful for developing revitalization therapies.

Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker.

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.

Comparison and correlation of cervical proprioception and muscle endurance in general joint hypermobility participants with and without non-specific neck pain-a cross-sectional study.

BackgroundCervical proprioception and muscle endurance are essential for maintaining cervical functional joint stability. Proprioception and muscle endurance may be impaired in those with general joint hypermobility (GJH). Examining these aspects is crucial. This study’s aims are to (1) compare the cervical joint position error (JPE) and muscle endurance holding capacities in GJH individuals with and without non-specific neck pain (NSNP) (2) to assess the relationship between hypermobility Beighton scores, cervical JPE’s, and muscle endurance in GJH individuals with and without NSNP.MethodsIn this cross-sectional comparative study, 33 GJH participants with NSNP (mean age 21.7 ± 1.8 years) and 35 asymptomatic participants GJH (mean age 22.42 ± 1.7 years) participated. Beighton’s score of ≥4 of 9 tests was used as criteria to diagnose GJH. Cervical JPEs were estimated in degrees using a cervical range of motion device, and muscle endurance (flexor and extensor) were estimated in seconds using a stopwatch.ResultsGJH participants with NSNP showed significantly larger cervical JPEs (p < 0.001) and decreased muscle endurance holding times (p < 0.001) compared to asymptomatic participants. Beighton hypermobility scores showed a significant moderate positive correlation with cervical JPEs (flexion: r = 0.43, p = 0.013), left rotation: r = 0.47, p = 0.005, right rotation: r = 0.57, p = 0.001) in NSNP individuals. Also, Beighton hypermobility scores showed a moderate negative correlation with muscle endurance in NSNP (flexor muscles: r = −0.40, p = 0.020, extensor muscles: r = −0.41, p = 0.020, and asymptomatic individuals (flexor muscles: −0.34, p = 0.045, extensor muscles: r = −0.45, p = 0.007).ConclusionGJH individuals with NSNP showed increased cervical JPEs and reduced muscle endurance compared to asymptomatic. Individuals with GJH with higher Beighton scores demonstrated increased cervical JPEs and reduced neck muscle endurance holding ability. In clinical practice, therapists should be aware of these findings, incorporate proprioceptive and muscle endurance assessments, and formulate rehabilitation strategies for NSNP individuals with GJM.

Relation of left atrial function with exercise capacity and muscle endurance in patients with heart failure.

AimsBoth left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial emptying fraction (LAEF).Methods and resultsWe analysed echocardiographic measurements, cardiopulmonary exercise testing (CPET), and isokinetic muscle function in 55 subjects with HF and controls [17 heart failure with preserved ejection fraction (HFpEF), 18 heart failure with reduced ejection fraction (HFrEF), and 20 healthy controls]. Patients with reduced LAEF showed reduced peak VO2: 14.3 ± 3.5 vs. 18.5 ± 3.5 mL/min/kg, P = 0.003, and reduced muscle endurance (RME): 64.3 ± 23.9 vs. 88.5 ± 32.3 Nm/kg, P = 0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) was associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, P = 0.012 vs. 0.63–0.98, P = 0.006, respectively). In a multiple linear regression, LAEF and working load measured during CPET (watt) were independent factors for RME after adjusting for age, LVGLS, and 6 min walk test (6MWT) [LAEF (B: 0.09, 95% CI: 1.01; 1.18, P = 0.024), working load (B: 0.05, 95% CI: 1.01; 1.08, P = 0.006)]. Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r = −0.6, P = 0.020). Endurance of the left leg was associated with LAEF (r = 0.79, P = 0.001) in patients with HFrEF.ConclusionsLAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful.

Relation of left atrial function with exercise capacity and muscle endurance in patients with heart failure

Abstract Aims Left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial ejection fraction (LAEF). Methods We analysed echocardiographic measurements, cardiopulmonary exercise testing, and isokinetic muscle function in 55 subjects with HF and controls (17 heart failure with preserved ejection fraction -HFpEF, 18 heart failure with reduced ejection fraction-HFrEF and 20 healthy controls). Results Patients with reduced LAEF showed reduced peak VO2: 14.3±3.5 vs. 18.5±3.5 ml/min/kg, p=0.003 and reduced muscle endurance (RME): 64.3±23.9 vs. 88.5±32.3 Nm/kg, p=0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) were associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, p=0.012 vs. 0.63–0.98, p=0.006, respectively). Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r=−0.6, p=0.020). Endurance of the left leg was associated with LAEF (r=0.79, p=0.001) in patients with HFrEF. Conclusion LAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful. Funding Acknowledgement Type of funding sources: None.

Kynurenine as a potential biomarker in detecting reduced muscle endurance: metabolomic profiling of patients with heart failure and exercise intolerance

Abstract Aims Reduced muscle endurance (RME) in patients with HFpEF and HFrEF is associated with structural and metabolic changes in skeletal muscle. We investigated the role of kynurenine (Kyn) as a potential marker in detecting RME. Additionally, we described the likely distorted metabolic pathways in serum in patients with RME and both preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods Fifty-five participants were prospectively recruited (17 HFpEF, 18 HFrEF outpatients and 20 healthy controls, HC). All participants underwent echocardiography, CPET, isokinetic muscle function tests. Quantification of metabolites in serum was performed using liquid chromatography tandem mass spectrometry. Results In a linear regression, Kyn was an independent predictor for RME after adjusting for alanine, glutamate, ornithine, spermine and short-chain-ACs (B: −8.2 per 1μM increase, 95% CI: −13.01, −3.30, p=0.001). Kyn showed 83% sensitivity and 70% specificity (area under the curve 0.83) in detecting RME. Patients with RME and HFpEF showed reduced levels of long-chain-, medium-chain-, medium-/long-chain-ACs ratios and alanine (p&amp;lt;0.05). In patients with RME and HFrEF we observed reduced concentrations of AAs (p&amp;lt;0.05). Compared to HC, patients with HFpEF and HFrEF had reduced amino acid (AA)-concentrations except for branched-chain and aromatic AAs, and higher concentrations of acylcarnitines (ACs) and Kyn (p&amp;lt;0.05). Conclusions Kyn shows high potential as biomarker for detecting RME. RME was associated with impaired fatty acid oxidation rates in HFpEF patients and with reduced concentrations of AAs in those with HFrEF. Funding Acknowledgement Type of funding sources: None.

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats.

What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres by upregulating peroxisome proliferator-activated receptor-γ coactivator-1α and activating the calcineurin-nuclear factor of activated T-cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse. Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7days before hindlimb unloading (HU) for 2weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured. Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.

Feasibility of a blended therapy approach in the treatment of patients with inflammatory myopathies

BackgroundInflammatory myopathies (IMs) are a group of rare conditions characterized by proximal and often symmetrical muscle weakness and reduced muscle endurance. The recommended medical treatment is based on corticosteroids in combination with immunosuppressants. This anti-inflammatory therapy serves to inhibit and prevent inflammation but does not influence impaired muscle strength. Exercise, particularly progressive resistance training, plays therefore an important role in IMs management. Blended therapy, a combination of face-to-face treatment and telerehabilitation, may be a powerful therapy option in improving exercise program adherence in these patients.MethodsThe feasibility of a 12-week interactive tablet-based home exercise program combined with face-to-face therapy sessions – a ‘blended therapy’ approach - was evaluated using a quasi-experimental one-group pre-post comparison design. Primary outcomes were recruitment, attrition and adherence rates, plus measures of acceptance (Technology Acceptance Model Questionnaire (TAM)) and satisfaction (satisfaction questionnaire). Secondary outcomes comprised potential effects of the intervention on muscle strength and function, activity limitation, disability and health-related quality of life.ResultsThirteen of the included 14 participants completed the study without any related adverse events. Mean adherence to exercise program was 84% (range: 25–100%) and participants indicated high acceptance of the intervention with mean TAM scores between 6.1 and 6.5 points. Overall satisfaction with the therapy sessions, the home program, and the technology was good. Approximately half the participants wished for longer training periods and more training sessions per week. There were inconsistent effects on muscle strength, muscle function, activity limitation, disability, and health-related quality of life.ConclusionBlended therapy combining the use of an interactive tablet-based resistance training program with face-to-face therapy sessions is feasible and safe and participants` acceptance with this approach was high. Furthermore, results were obtained that might be useful in selecting appropriate assessments and sample sizes in future trials.Trial registrationNCT03713151.

Mitochondrial Capacity and Muscle Endurance in Individuals with Parkinson’s Disease

Introduction: Parkinson's disease (PD) is associated with loss of motor control and difficulty exercising. This study measured skeletal muscle mitochondrial capacity and endurance in individuals with and without PD using novel non-invasive methods. We hypothesized that individuals with PD will have decreased mitochondrial capacity, reduced oxygen recovery, and decreased endurance compared to controls. Methods: Eight participants with PD and nine healthy controls were tested. Mitochondrial capacity was measured as the rate of recovery of muscle metabolism after electrical stimulation using near-infrared spectroscopy (NIRS) and repeated short arterial occlusions. Oxygen recovery was measured as the half time of recovery of oxygen levels after 5 minutes of ischemia. Muscle endurance was determined from changes in twitch contraction acceleration during electrical stimulation at 2, 4, and 6 Hz. Results: Mitochondrial capacity was lower in individuals with PD compared to controls (1.5±0.1min-1 vs. 1.7±0.1min-1, p=0.02). Individuals with PD had slower oxygen recovery after ischemia compared to controls (8.9±2.3s vs. 5.4±0.8s, p=0.01). Endurance was not different between groups at 6 Hz (PD vs controls: 58±23% vs. 69±16%, p=0.34). The effect sizes for mitochondrial capacity and oxygen recovery were large (Cohen's d &gt;0.8). The Cohen's d for endurance was 1.11. Conclusion: Individuals with PD had slight impairments in mitochondrial capacity and blood flow but did not have reduced muscle endurance. While our study suggests that muscle metabolic dysfunction may play a minor role in exercise intolerance in people with PD, it demonstrates the use of noninvasive technologies to evaluate muscle function in people with neurological disorders.

Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction.

Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P=0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size (P<0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC (P<0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, -54.3 (95% CI, -106 to -2.00), P=0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90-96.77), P=0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90-61.78), P<0.001]). Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

Simultaneous Measurement of Perfusion and T2* in Calf Muscle at 7T with Submaximal Exercise using Radial Acquisition

Impairments in oxygen delivery and consumption can lead to reduced muscle endurance and physical disability. Perfusion, a measure of microvascular blood flow, provides information on nutrient delivery. T2* provides information about relative tissue oxygenation. Changes in these parameters following stress, such as exercise, can yield important information about imbalance between delivery and consumption. In this study, we implemented novel golden angle radial MRI acquisition technique to simultaneously quantify muscle perfusion and T2* at 7T with improved temporal resolution, and demonstrated assessment of spatial and temporal changes in these parameters within calf muscles during recovery from plantar flexion exercise. Nine healthy subjects participated the studies. At rest, perfusion and T2* in gastrocnemius muscle group within calf muscle were 5 ± 2 mL/100 g/min and 21.1 ± 3 ms respectively. Then the subjects performed plantar flexion exercise producing a torque of ~8ft-lb. Immediately after the exercise, perfusion was elevated to 79.3 ± 9 mL/100 g/min and T2* was decreased by 6 ± 3%. The time constants for 50% perfusion and T2* recovery were 54.1 ± 10 s and 68.5 ± 7 s respectively. These results demonstrate successful simultaneous quantification of perfusion and T2* in skeletal muscle using the developed technique.

Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial

BackgroundIn people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen.MethodsThis is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events.DiscussionThe proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD.Trial registrationClinicalTrials.gov, ID: NCT03518723. Registered on 13 April 2018.

The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle

ObjectiveMitochondria are organelles primarily responsible for energy production, and recent evidence indicates that alterations in size, shape, location, and quantity occur in response to fluctuations in energy supply and demand. We tested the impact of acute and chronic exercise on mitochondrial dynamics signaling and determined the impact of the mitochondrial fission regulator Dynamin related protein (Drp)1 on exercise performance and muscle adaptations to training. MethodsWildtype and muscle-specific Drp1 heterozygote (mDrp1+/−) mice, as well as dysglycemic (DG) and healthy normoglycemic men (control) performed acute and chronic exercise. The Hybrid Mouse Diversity Panel, including 100 murine strains of recombinant inbred mice, was used to identify muscle Dnm1L (encodes Drp1)-gene relationships. ResultsEndurance exercise impacted all aspects of the mitochondrial life cycle, i.e. fission-fusion, biogenesis, and mitophagy. Dnm1L gene expression and Drp1Ser616 phosphorylation were markedly increased by acute exercise and declined to baseline during post-exercise recovery. Dnm1L expression was strongly associated with transcripts known to regulate mitochondrial metabolism and adaptations to exercise. Exercise increased the expression of DNM1L in skeletal muscle of healthy control and DG subjects, despite a 15% ↓(P = 0.01) in muscle DNM1L expression in DG at baseline. To interrogate the role of Dnm1L further, we exercise trained male mDrp1+/− mice and found that Drp1 deficiency reduced muscle endurance and running performance, and altered muscle adaptations in response to exercise training. ConclusionOur findings highlight the importance of mitochondrial dynamics, specifically Drp1 signaling, in the regulation of exercise performance and adaptations to endurance exercise training.

Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass.

BackgroundAcrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro. The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear.MethodsC2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro. Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration.ResultsNon‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P < 0.05). The protein expression for myogenesis‐related signalling molecules (myogenin and phosphorylated Akt: 0.5 and 1 μM, 85.15% and 51.52% control and 62.63% and 56.57% control, respectively, n = 4, P < 0.05) and myosin heavy chain (MHC: 0.5 and 1 μM, 63.64% and 52.53% control, n = 4, P < 0.05) were decreased in acrolein‐treated myoblasts. Over‐expression of the constitutively active form of Akt in myoblasts during differentiation prevented the inhibitory effects of acrolein (1 μM) on myogenesis (MHC and myogenin protein expression: acrolein with or without constitutively active Akt, 64.65% and 105.21% control and 69.14% and 102.02% control, respectively, n = 5, P < 0.05). Oral administration of acrolein for 4 weeks reduced muscle weights (5 mg/kg/day: 65.52% control, n = 6, P < 0.05) and cross‐sectional area of myofibers in soleus muscles (5 mg/kg/day: 79.92% control, n = 6, P < 0.05) with an up‐regulation of atrogin‐1 and a down‐regulation of phosphorylated Akt protein expressions. Acrolein retarded soleus muscle regeneration in a glycerol‐induced muscle regeneration mouse model (5 mg/kg/day: 49.29% control, n = 4, P < 0.05). Acrolein exposure reduced muscle endurance during rotarod fatigue performance in mice with or without glycerol‐induced muscle injury (5 mg/kg/day without glycerol: 30.43% control, n = 4, P < 0.05). Accumulation of acrolein protein adducts could be detected in the soleus muscles of acrolein‐treated mice.ConclusionsLow‐dose acrolein significantly inhibited myogenic differentiation in vitro, which might be through inhibition of Akt signalling. Acrolein induced muscle wasting and retarded muscle regeneration in mice. These results suggest that acrolein may be a risk factor for myogenesis and disease‐related myopathy.

Effects of long-term respiratory muscle endurance training on respiratory and functional outcomes in patients with Myasthenia gravis.

Myasthenia gravis (MG) is characterized by reduced muscle endurance and often leads to respiratory complications. A long-term respiratory muscle endurance training (RMET) based on normocapnic hyperpnea was introduced for the first time in MG patients. We investigated RMET effects on respiratory endurance (RE), MG symptoms, lung function and physical fitness and compared the results with a control group (CG). The training period consisted of four weeks intensive training (IT; five 30-min training sessions per week) followed by twelve months maintenance training (MT; five 30-min training sessions over two weeks). Eighteen patients with mild to moderate MG participated as the training group (TG), six patients served as CG. RE, lung function, MG score and physical fitness were tested before and after IT and after three to twelve months of MT. Only 12 TG patients completed the entire training period. Thirteen months of training significantly increased RE measured as time until exhaustion (Tlim) to 412% of baseline (P < 0.001). The MG score improved from 0.67±0.09 to 0.41 ± 0.1 (p = 0.004), and the number of squats per minute as a measure of physical fitness increased in the TG to 160% of baseline (p = 0.015). While lung function did not change during the training period, we observed a modulation in the breathing pattern at rest with prolonged expiration (122% of baseline, p = 0.028). In addition, TG reported subjective improvements in MG symptoms, respiratory symptoms and physical fitness by 49%, 58% and 64%, respectively (P < 0.001). No significant changes were observed in the CG. This is the first controlled long-term RMET study in MG patients. The results demonstrated that this normocapnic hyperpnea training is feasible and beneficial for patients with mild to moderate MG and is a valuable supplement to conventional drug treatment.

Muscle endurance, strength, and active range of motion in patients with different subphenotypes in systemic sclerosis: a cross-sectional cohort study

Objective: Proximal muscle weakness is common in patients with systemic sclerosis (SSc). Dynamic muscle endurance, muscle strength in the lower extremities, and active range of motion (AROM) in the upper extremities are less studied. We investigated functional muscle endurance, strength, and AROM, and explored differences depending on skin and/or lung involvement in SSc patients.Method: The study divided 205 patients with limited/diffuse cutaneous systemic sclerosis (lcSSc/dcSSc) into no–mild and moderate–end-stage lung involvement, the latter based on the Medsger disease severity score. Dynamic muscle endurance in shoulder and hip flexion was assessed by the Functional Index-2, lower extremity muscle strength by the Timed-Stands Test (TST), and shoulder–arm AROM by the Functional Shoulder Assessment (FSA).Results: Shoulder and hip flexion muscle endurance were reduced in relation to reference values median (IQR) [53% (27–100%) and 40% (23–90%), respectively, p < 0.001]. Patients with moderate–end-stage lung involvement had less endurance in shoulder [39% (21–71%) and hip flexion 35% (20–70%)] than patients with no-mild lung involvement [57% (33–99%) and 48% (28–100%), p < 0.05]. All patients, regardless of subtype/grouping, needed longer to complete the TST [21 s (17–27 s)] compared to reference values [17 s (15–18 s), p < 0.001], and patients with moderate-end-stage lung involvement had worse TST score than patients with no-mild lung involvement, [25 s (18–30 s) vs 19 s (16–25 s), p < 0.001]. The FSA sum scores were lower compared with reference values (p < 0.01). DcSSc patients had a lower FSA-sum score [53 (48–57)] than lcSSc patients [57 (52–60), p < 0.01].Conclusion: SSc patients have markedly reduced muscle endurance in the upper and lower extremities, reduced muscle strength in the lower extremities, and impaired AROM in the shoulders and arms. Patients with moderate–end-stage lung involvement had more impaired muscle endurance and strength but no differences were found between lcSSc and dcSSc patients. Not only muscle strength, but also dynamic muscle endurance should be measured in SSc patients.

The 'aerobic/resistance/inspiratory muscle training hypothesis in heart failure'.

Evidence from large multicentre exercise intervention trials in heart failure patients, investigating both moderate continuous aerobic training and high intensity interval training, indicates that the 'crème de la crème' exercise programme for this population remains to be found. The 'aerobic/resistance/inspiratory (ARIS) muscle training hypothesis in heart failure' is introduced, suggesting that combined ARIS muscle training may result in maximal exercise pathophysiological and functional benefits in heart failure patients. The hypothesis is based on the decoding of the 'skeletal muscle hypothesis in heart failure' and on revision of experimental evidence to date showing that exercise and functional intolerance in heart failure patients are associated not only with reduced muscle endurance, indication for aerobic training (AT), but also with reduced muscle strength and decreased inspiratory muscle function contributing to weakness, dyspnoea, fatigue and low aerobic capacity, forming the grounds for the addition of both resistance training (RT) and inspiratory muscle training (IMT) to AT. The hypothesis will be tested by comparing all potential exercise combinations, ARIS, AT/RT, AT/IMT, AT, evaluating both functional and cardiac indices in a large sample of heart failure patients of New York Heart Association class II-III and left ventricular ejection fraction ≤35% ad hoc by the multicentre randomized clinical trial, Aerobic Resistance, InSpiratory Training OutcomeS in Heart Failure (ARISTOS-HF trial).

Power reserve following ramp-incremental cycling to exhaustion: implications for muscle fatigue and function.

In ramp-incremental cycling exercise, some individuals are capable of producing power output (PO) in excess of that produced at their limit of tolerance (LoT) whereas others cannot. This study sought to describe the 1) prevalence of a "power reserve" within a group of young men ( n = 21; mean ± SD: age 25 ± 4 yr; V̇o2max 45 ± 8 ml·kg-1·min-1); and 2) muscle fatigue characteristics of those with and without a power reserve. "Power reserve" (ΔPReserve) was determined as the difference between peak PO achieved during a ramp-incremental test to exhaustion and maximal, single-leg isokinetic dynamometer power determined within 45 s of completing the ramp-incremental test. Between-group differences in pre- vs. postexercise changes in voluntary and electrically stimulated single-leg muscle force production measures (maximal voluntary contraction torque, voluntary activation, maximal isotonic velocity and isokinetic power; 1-, 10-, 50-Hz torque; and 10/50-Hz ratio), V̇o2max, and constant-PO cycling time-to-exhaustion also were assessed. Frequency distribution analysis revealed a dichotomy in the prevalence of a power reserve within the sample resulting in two groups: 1) "No Reserve" (NRES: power reserve <5%; n = 10) and 2) "Reserve" (RES: power reserve >15%; n = 11). At the LoT, all participants had achieved V̇o2max. Muscle fatigue was evident in both groups, although the NRES group had greater reductions ( P < 0.05) in 10-Hz peak torque (PT), 10/50 Hz ratio, and maximal velocity. Time to the LoT during the constant PO test was 22 ± 16% greater ( P < 0.05) in RES (116 ± 19 s; PO = 317 ± 52 W) than in NRES (90 ± 23 s; PO = 337 ± 71 W), despite similar ramp-incremental exercise durations and V̇o2max between groups. Compared with the RES group, the NRES group accrued greater peripheral muscle fatigue at the LoT, suggesting that the mechanisms contributing to exhaustion in a ramp-incremental protocol are not uniform. NEW & NOTEWORTHY This study demonstrates that the mechanisms associated with the limit of tolerance during ramp-incremental cycling exercise differ between those who are capable of generating power output in excess of that at exercise termination vs. those who are not. Those without a "power reserve" exhibit greater peripheral muscle fatigue and reduced muscle endurance, supporting the hypothesis that exhaustion occurs at a specific level of neuromuscular fatigue. In contrast, those with a power reserve likely are limited by other mechanisms.

Relation between upper-limb muscle strength with exercise capacity, quality of life and dyspnea in patients with severe chronic obstructive pulmonary disease.

In chronic obstructive pulmonary disease (COPD), skeletal muscle weakness is characterized by reduced muscle strength, reduced muscle endurance and the presence of muscle fatigue especially in lower limbs. There has been little research into the upper limb skeletal muscles. In this study, we aimed to investigate the relation of upper limb muscle strength with pulmonary function, exercise capacity, quality of life (QoL) and dyspnea sensation. Eigthy-eight patients (89.8% male; age: 64.2 ± 8.7 years) with COPD (FEV1 = 34.2% ± 15.2%) were evaluated. Tests included hand grip strength and actual 1-repetition maximum (1RM) test for upper limb strength. Dyspnea sensation was assessed with medical research council (MRC) scale. St. George Respiratory Questionary (SGRQ) was used to evaluate patients health related QoL. Exercise capacity was evaluated with incremental shuttle walk test and endurance shuttle walk test. Upper limb muscle strength correlated with exercise capacity but no correlations were found with pulmonary functions.There were negative correlations with all the domains of SGRQ both actual 1RM and handgrip strength. MRC scores revealed a negative correlation with upper limb muscle strength. In our study, we showed that upper limb muscle strength correlated with exercise capacity, QoL, dyspnea sensation. Identifying patients who have greater reductions in strength will allow early interventions with a multidisciplinary manner.

Overweight, a culprit affecting back endurance: A cross sectional study

Background: Studies reveal that reduced muscle endurance has a major impact, leading to decrease in quality of life. Hence early diagnosis and prognosis is essential for leading healthy life. Lack of muscle endurance has shown to be related to decreased proprioceptive awareness and decreased productivity in the workplace and daily activity. Hence, the purpose of this study was to evaluate isometric endurance time of healthy normal population for trunk extensors and flexors. Method: In this cross-sectional study, 100 participants were randomly recruited by convenient sampling and trunk muscle endurance was assessed using trunk flexor endurance test and Sorensen's test. Results: The results of the study revealed-mean back endurance for extensor muscles was 47.66secs and 52.82secs for males and females respectively. Similarly, for trunk endurance for trunk flexors was 52.82 secs and 112.86 secs for males and females respectively. Conclusion: The study concluded that trunk muscle endurance for females was more as compared to males and also, with increase in BMI there is decrease in trunk muscle endurance. KEYWORDS: Trunk endurance; BMI; Sorensen's test; Trunk.