Skeletal muscle responses to lower limb suspension in humans

Hather, Bruce M.; Adams, Gregory R.; Tesch, Per A.; Dudley, Gary A.

doi:10.1152/jappl.1992.72.4.1493

Cited by 174 publications

(187 citation statements)

References 19 publications

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“…Muscle weakness following immobilization by a full‐length leg cast was mainly due to the marked decrease in the maximum voluntary force (neurogenic muscle activation) rather than loss of TMV 43. This mechanism is supported by the consistent observation that the loss of voluntary muscle strength is greater than that of muscle cross‐sectional area 44, 45. Muscle strength recovered in a similar manner in both the bimagrumab and placebo groups, seemingly independent of the rate and magnitude of TMV changes.…”

Section: Discussionmentioning

confidence: 88%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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BackgroundPatients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.MethodsIn this double‐blind, placebo‐controlled trial, healthy young men (n = 24; mean age, 24.1 years) were placed in a full‐length cast of one of the lower extremities for 2 weeks to induce disuse atrophy. After cast removal, subjects were randomized to receive a single intravenous (i.v.) dose of either bimagrumab 30 mg/kg (n = 15) or placebo (n = 9) and were followed for 12 weeks. Changes in thigh muscle volume (TMV) and inter‐muscular adipose tissue (IMAT) and subcutaneous adipose tissue (SCAT) of the thigh, maximum voluntary knee extension strength, and safety were assessed throughout the 12 week study.ResultsCasting resulted in an average TMV loss of −4.8% and comparable increases in IMAT and SCAT volumes. Bimagrumab 30 mg/kg i.v. resulted in a rapid increase in TMV at 2 weeks following cast removal and a +5.1% increase above pre‐cast levels at 12 weeks. In comparison, TMV returned to pre‐cast level at 12 weeks (−0.1%) in the placebo group. The increased adiposity of the casted leg was sustained in the placebo group and decreased substantially in the bimagrumab group at Week 12 (IMAT: −6.6%, SCAT: −3.5%). Knee extension strength decreased by ~25% in the casted leg for all subjects and returned to pre‐cast levels within 6 weeks after cast removal in both treatment arms. Bimagrumab was well tolerated with no serious or severe adverse events reported during the study.ConclusionsA single dose of bimagrumab 30 mg/kg i.v. safely accelerated the recovery of TMV and reversal of accumulated IMAT following 2 weeks in a joint‐immobilizing cast.

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Section: Discussionmentioning

confidence: 88%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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“…23,24 For example, knee extensor muscle CSA was reduced by 14% following 6 weeks of bed rest, 23 and the thigh muscle CSA decreased 12% after 6 weeks of unilateral lower limb suspension. 24 The magnitude of skeletal muscle atrophy reported in this study indicates that incomplete SCI could evoke greater disuse than previous reported models of microgravity. Furthermore, skeletal muscle atrophy was even more pronounced by 6% after correcting for IMF.…”

Section: Discussionmentioning

confidence: 98%

“…Previously, MRI was used to quantify skeletal muscle response to unloading and after SCI. [1][2][3][4]23,24 The accuracy of MRI versus dual-energy X-ray absorptiometery (DEXA) in determining skeletal muscle atrophy has been previously investigated showing that DEXA overestimates the proportion of the muscle in fat-free mass after SCI and inaccurately reflects the degree of muscle atrophy compared to MRI. 3 MRI also provides the advantage over computed tomography (CT) by facilitating the acquisition of multiple slices over a single slice commonly used in CT scans, which can inaccurately represent the exact changes in muscle size in response to training or disuse.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury

2006

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“…The subjects were highly motivated, and all had prior experience with knee-extension MVC. We have previously established that the VL muscle constitutes roughly 30% of the total quadriceps group cross-sectional area (28). Accordingly, electrical current sufficient to elicit ϳ30% of the observed isometric knee-extension MVC was determined and used for the subsequent EMS protocol in the AB subjects.…”

Section: Subjectsmentioning

confidence: 99%

“…Muscle samples were obtained from all subjects immediately before the initial stimulation and 24 h after the second stimulation bout. Biopsies were taken from the VL by using the percutaneous biopsy technique, as done previously (16,28). Samples were immediately cooled with liquid nitrogen and then stored at Ϫ70°C until analyzed.…”

Section: Subjectsmentioning

confidence: 99%

Acute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjects

Bickel

Slade

Haddad

et al. 2003

Journal of Applied Physiology

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. Acute molecular responses of skeletal muscle to resistance exercise in ablebodied and spinal cord-injured subjects. J Appl Physiol 94: 2255-2262. First published February 28, 2003 10.1152/japplphysiol.00014.2003.-Spinal cord injury (SCI) results in muscle atrophy, which contributes to a number of health problems, such as cardiovascular deconditioning, metabolic derangement, and osteoporosis. Electromyostimulation (EMS) holds the promise of ameliorating SCI-related muscle atrophy and, therefore, improving general health. To date, EMS training of long-term SCI subjects has resulted in some muscle hypertrophy but has fallen short of normalizing muscle mass. The aim of this study was to compare the molecular responses of vastus lateralis muscles from able-bodied (AB) and SCI subjects after acute bouts of EMS-induced resistance exercise to determine whether SCI muscles displayed some impairment in response. Analysis included mRNA markers known to be responsive to increased loading in rodent muscles. Muscles of AB and SCI subjects were subjected to EMS-stimulated exercise in two 30-min bouts, separated by a 48-h rest. Needle biopsy samples were obtained 24 h after the second exercise bout. In both the AB and SCI muscles, significant changes were seen in insulin-like growth factor binding proteins 4 and 5, cyclin-dependent kinase inhibitor p21, and myogenin mRNA levels. In AB subjects, the mRNA for mechano-growth factor was also increased. Before exercise, the total RNA concentration of the SCI muscles was less than that of the AB subjects but not different postexercise. The results of this study indicate that acute bouts of resistance exercise stimulate molecular responses in the skeletal muscles of both AB and SCI subjects. The responses seen in the SCI muscles indicate that the systems that regulate these molecular responses are intact, even after extended periods of muscle unloading. mechano-growth factor; insulin-like growth factor I; insulinlike growth factor binding protein; myogenin INACTIVITY CAN LEAD TO A LOSS of muscle mass and function. Complete spinal cord injury (SCI) leads to inactivation and profound muscle unloading. The muscles of SCI patients are characterized by severe atrophy, as well as extensively altered metabolic and contractile protein profiles (6,19,40). For example, within several months of SCI, muscles and their constituent myofibers can be reduced to ϳ41% of the size of those of able-bodied (AB) individuals (16, 15). The loss in muscle mass and function can contribute to a number of health problems, such as decreased cardiorespiratory fitness, impaired glucose tolerance, and osteoporosis (37, 39).Recognition of potential benefits to be garnered by maintaining or increasing muscle mass in SCI patients has lead to a number of studies aimed at using electromyostimulation (EMS) to induce contractile activity in the muscles of these patients. In AB subjects, EMSinduced resistance exercise has been shown to result in increases in muscle size and performance (13,14,41). Studies have also shown...

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Skeletal muscle responses to lower limb suspension in humans

Cited by 174 publications

References 19 publications

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury

Acute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjects

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