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      Impact of transcutaneous neuromuscular electrical stimulation or resistance exercise on skeletal muscle mRNA expression in COPD

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          Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but little comparative data are available. This study, therefore, investigated changes in muscle mRNA abundance of a number of gene targets in response to a single bout of NMES compared with RE.

          Methods: Twenty-six patients with stable COPD (15 male; FEV 1, 43±18% predicted; age, 64±8 years; fat free mass index, 16.6±1.8 kg/m 2) undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance) or 5×30 maximal voluntary isokinetic knee extensions. Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after intervention. Expression of 384 targeted mRNA transcripts was assessed by real time TaqMan PCR. Significant change in expression from baseline was determined using the ΔΔC T method with a false discovery rate (FDR) of <5%.

          Results: NMES and RE altered mRNA abundance of 18 and 68 genes, respectively (FDR <5%), of which 14 genes were common to both interventions and of the same magnitude of fold change. Biological functions of upregulated genes included inflammation, hypertrophy, muscle protein turnover, and muscle growth, whilst downregulated genes included mitochondrial and cell signaling functions.

          Conclusions: Compared with NMES, RE had a broader impact on mRNA abundance and, therefore, appears to be the superior intervention for maximizing transcriptional responses in the quadriceps of patients with COPD. However, if voluntary RE is not feasible in a clinical setting, NMES by modifying expression of genes known to impact upon muscle mass and strength may have a positive influence on muscle function.

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          Peripheral muscle weakness in patients with chronic obstructive pulmonary disease.

          Peripheral muscle weakness is commonly found in patients with chronic obstructive pulmonary disease (COPD) and may play a role in reducing exercise capacity. The purposes of this study were to evaluate, in patients with COPD: (1) the relationship between muscle strength and cross-sectional area (CSA), (2) the distribution of peripheral muscle weakness, and (3) the relationship between muscle strength and the severity of lung disease. Thirty-four patients with COPD and 16 normal subjects of similar age and body mass index were evaluated. Compared with normal subjects, the strength of three muscle groups (p < 0.05) and the right thigh muscle CSA, evaluated by computed tomography (83.4 +/- 16.4 versus 109.6 +/- 15.6 cm2, p < 0.0001), were reduced in COPD. The quadriceps strength/thigh muscle CSA ratio was similar for the two groups. The reduction in quadriceps strength was proportionally greater than that of the shoulder girdle muscles (p < 0.05). Similar observations were made whether or not patients had been exposed to systemic corticosteroids in the 6-mo period preceding the study, although there was a tendency for the quadriceps strength/thigh muscle CSA ratio to be lower in patients who had received corticosteroids. In COPD, quadriceps strength and muscle CSA correlated positively with the FEV1 expressed in percentage of predicted value (r = 0.55 and r = 0. 66, respectively, p < 0.0005). In summary, the strength/muscle cross-sectional area ratio was not different between the two groups, suggesting that weakness in COPD is due to muscle atrophy. In COPD, the distribution of peripheral muscle weakness and the correlation between quadriceps strength and the degree of airflow obstruction suggests that chronic inactivity and muscle deconditioning are important factors in the loss in muscle mass and strength.
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            Excitability and inhibitability of motoneurons of different sizes.

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              Myofibre damage in human skeletal muscle: effects of electrical stimulation versus voluntary contraction.

              Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in humans using voluntary exercise. Untrained males (n=8, range 22-27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior to exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast, a significant disruption of cytoskeletal proteins (desmin) and a rise of myogenic growth factors (myogenin) occurred only in ES. Intracellular disruption and destroyed Z-lines were markedly more pronounced in ES (40%) compared with VOL (10%). Likewise, the increase in satellite cell markers [neural cell adhesion molecule (N-CAM) and paired-box transcription factor (Pax-7)] was more pronounced in ES versus VOL. Finally, staining of the intramuscular connective tissue (tenascin C) was increased equally in ES and VOL after exercise. The present study demonstrates that in human muscle, the delayed onset of muscle soreness was not significantly different between the two treatments despite marked differences in intramuscular histological markers, in particular myofibre proteins and satellite cell markers. An increase in tenascin C expression in the midbelly of the skeletal muscle in both legs provides further evidence of a potential role for the extracellular matrix in the phenomenon of delayed onset of muscle soreness.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                28 June 2019
                : 14
                : 1355-1364
                [1 ] Department of Respiratory Sciences, University of Leicester , Leicester, UK
                [2 ] Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital , Leicester, UK
                [3 ] Medical Research Council/Arthritis Research UK (MRC/ARUK) Centre for Musculoskeletal Ageing Research, University of Nottingham , Nottingham, UK
                [4 ] Centre for Sport, Exercise and Osteoarthritis Research, University of Nottingham , Nottingham, UK
                [5 ] NIHR Nottingham Biomedical Research Centre, University of Nottingham , Nottingham, UK
                [6 ] Peterborough and Stamford Hospitals NHS Foundation Trust, Peterborough City Hospital , Bretton, UK
                [7 ] Barking, Havering and Redbridge University Hospitals NHS Trust, Chest Clinic, King George Hospital , Ilford, UK
                Author notes
                Correspondence: Paul L GreenhaffNational Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Division of Physiology, Pharmacology and Neuroscience, The Medical School, University of Nottingham, Queen’s Medical Centre , NottinghamNG7 2UH, UKTel +44 11 5823 0133Email paul.greenhaff@

                These authors contributed equally to this work

                © 2019 Latimer et al.

                This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 2, Tables: 2, References: 57, Pages: 10
                Original Research

                Respiratory medicine

                resistance exercise, copd, gene expression, skeletal muscle, nmes


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