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Dietary protein intake does not modulate daily myofibrillar protein synthesis rates or loss of muscle mass and function during short-term immobilization in young men: a randomized controlled trial.
Kilroe, SP, Fulford, J, Jackman, S, Holwerda, A, Gijsen, A, van Loon, L, Wall, BT
The American journal of clinical nutrition. 2021;(3):548-561
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Abstract
BACKGROUND Short-term (<1 wk) muscle disuse lowers daily myofibrillar protein synthesis (MyoPS) rates resulting in muscle mass loss. The understanding of how daily dietary protein intake influences such muscle deconditioning requires further investigation. OBJECTIVES To assess the influence of graded dietary protein intakes on daily MyoPS rates and the loss of muscle mass during 3 d of disuse. METHODS Thirty-three healthy young men (aged 22 ± 1 y; BMI = 23 ± 1 kg/m2) initially consumed the same standardized diet for 5 d, providing 1.6 g protein/kg body mass/d. Thereafter, participants underwent a 3-d period of unilateral leg immobilization during which they were randomly assigned to 1 of 3 eucaloric diets containing relatively high, low, or no protein (HIGH: 1.6, LOW: 0.5, NO: 0.15 g protein/kg/d; n = 11 per group). One day prior to immobilization participants ingested 400 mL deuterated water (D2O) with 50-mL doses consumed daily thereafter. Prior to and immediately after immobilization upper leg bilateral MRI scans and vastus lateralis muscle biopsies were performed to measure quadriceps muscle volume and daily MyoPS rates, respectively. RESULTS Quadriceps muscle volume of the control legs remained unchanged throughout the experiment (P > 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P < 0.05) of the immobilized leg in the HIGH, LOW, and NO groups (P < 0.05), respectively, with no significant differences between groups (P > 0.05). D2O ingestion resulted in comparable plasma free [2H]-alanine enrichments during immobilization (∼2.5 mole percentage excess) across groups (P > 0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P > 0.05). CONCLUSIONS Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses.Clinical trial registry number: NCT03797781.
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Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14-days of limb immobilization.
Cohen, JN, Slysz, JT, King, TJ, Coates, AM, King, RT, Burr, JF
European journal of applied physiology. 2021;(9):2437-2447
Abstract
PURPOSE Limb immobilization causes local vasculature to experience detrimental adaptations. Simple strategies to increase blood flow (heating, fidgeting) successfully prevent acute (≤ 1 day) impairments; however, none have leveraged the hyperemic response over prolonged periods (weeks) mirroring injury rehabilitation. Throughout a 14-day unilateral limb immobilization, we sought to preserve vascular structure and responsiveness by repeatedly activating a reactive hyperemic response via blood flow restriction (BFR) and amplifying this stimulus by combining BFR with electric muscle stimulation (EMS). METHODS Young healthy adults (M:F = 14:17, age = 22.4 ± 3.7 years) were randomly assigned to control, BFR, or BFR + EMS groups. BFR and BFR + EMS groups were treated for 30 min twice daily (3 × 10 min ischemia-reperfusion cycles; 15% maximal voluntary contraction EMS), 5 days/week (20 total sessions). Before and after immobilization, artery diameter, flow-mediated dilation (FMD) and blood flow measures were collected in the superficial femoral artery (SFA). RESULTS Following immobilization, there was less retrograde blood velocity (+ 1.8 ± 3.6 cm s-1, P = 0.01), but not retrograde shear (P = 0.097). All groups displayed reduced baseline and peak SFA diameter following immobilization (- 0.46 ± 0.41 mm and - 0.43 ± 0.39 mm, P < 0.01); however, there were no differences by group or across time for FMD (% diameter change, shear-corrected, or allometrically scaled) nor microvascular function assessed by peak flow capacity. CONCLUSION Following immobilization, our results reveal (1) neither BFR nor BFR + EMS mitigate artery structure impairments, (2) intervention-induced shear stress did not affect vascular function assessed by FMD, and (3) retrograde blood velocity is reduced at rest offering potential insight to mechanisms of flow regulation. In conclusion, BFR appears insufficient as a treatment strategy for preventing macrovascular dysfunction during limb immobilization.
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Microvascular Function Is Impaired after Short-Term Immobilization in Healthy Men.
Rytter, N, Piil, P, Carter, H, Nyberg, M, Hellsten, Y, Gliemann, L
Medicine and science in sports and exercise. 2020;(10):2107-2116
Abstract
PURPOSE We examined whether 2 wk of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function. METHODS Study participants were healthy young men (n = 12; 20-24 yr of age). Leg microvascular function was determined before the intervention, after the immobilization period, and after a 4-wk exercise training period. Microvascular function was assessed as the vasodilator response to intra-arterial infusion of acetylcholine and sodium nitroprusside and as the vasoconstrictor response to endogenous noradrenaline release induced by tyramine infusion. Vasodilator enzymes as well as prooxidant and antioxidant enzymes were assessed by protein analysis in skeletal muscle samples: endothelial nitric oxide synthase, NADPH oxidase (NOX p67 and NOX gp91), and superoxide dismutase 2 (SOD2). RESULTS The acetylcholine-induced change in vascular conductance was reduced after the 2 wk of immobilization (P = 0.003), tended to increase (P = 0.061), and was back to baseline levels after the subsequent 4 wk of exercise training. Plasma prostacyclin levels in response to acetylcholine infusion were lower after immobilization than before (P = 0.041). The changes in vascular conductance with sodium nitroprusside and tyramine were similar during all conditions. Skeletal muscle protein levels of endothelial nitric oxide synthase in the experimental leg were unchanged with immobilization and subsequent training but increased 47% in the control leg with training (P = 0.002). NOX p67, NOX gp91, and SOD2 in the experimental leg remained unaltered with immobilization, and SOD2 was higher than preimmobilization after 4 wk of training (P < 0.001). CONCLUSIONS The study shows that 2 wk of immobilization impairs leg microvascular endothelial function and prostacyclin formation but that 4 wk of intense aerobic exercise training restores the function. The underlying mechanism may reside in the prostacyclin system.
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The mechanisms and treatments of muscular pathological changes in immobilization-induced joint contracture: A literature review.
Wang, F, Zhang, QB, Zhou, Y, Chen, S, Huang, PP, Liu, Y, Xu, YH
Chinese journal of traumatology = Zhonghua chuang shang za zhi. 2019;(2):93-98
Abstract
The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca2+-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
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Impact of dairy protein during limb immobilization and recovery on muscle size and protein synthesis; a randomized controlled trial.
Mitchell, CJ, D'Souza, RF, Mitchell, SM, Figueiredo, VC, Miller, BF, Hamilton, KL, Peelor, FF, Coronet, M, Pileggi, CA, Durainayagam, B, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2018;(3):717-728
Abstract
Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (-24.7 ± 2.7%), partially recovered with AR (-8.6 ± 2.6%), and fully recovered after RT (-0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (-4.1 ± 0.5%), partially recovered with AR (-2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.
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Cytokine IL1α and lactate as markers for tissue damage in spineboard immobilisation. A prospective, randomised open-label crossover trial.
Hemmes, B, de Wert, LA, Brink, PRG, Oomens, CWJ, Bader, DL, Poeze, M
Journal of the mechanical behavior of biomedical materials. 2017;:82-88
Abstract
BACKGROUND Spinal immobilisation using a rigid long spineboard is a well-established procedure in trauma care. During immobilisation, the body is exposed to high tissue-interface pressures. This may lead to a localised inflammatory response of the skin, which may be used to monitor the body's response to different types of immobilisation device. AIM: In this study we compared the standard rigid spineboard with a new soft-layered spineboard regarding tissue-interface pressures, skin redness as an indicator of reactive hyperaemia and cutaneous IL1α and lactate release. METHODS Twelve healthy male participants were asked to lie supine on both a rigid and a soft-layered spineboard, loading the sacrum for one hour, followed by one hour in unloaded position. Tissue-interface pressures on the buttocks during loading were measured continuously using a pressure mapping mat. Cutaneous IL1α and lactate concentrations were assessed using Sebutapes, during 20-min periods. After each 20-min period, a photo of the buttocks was taken, which was later assessed for redness by two observers. RESULTS Significant differences in tissue-interface pressure and reactive hyperaemia were found between the two types of spineboard. Release of IL1α and lactate were found to increase with prolonged exposure to pressure, and to decrease in the unloaded prone position. A significant relationship was found between tissue-interface pressure and reactive hyperaemia, but not with IL1α nor lactate release. Time course of IL1α and lactate release was similar for both types of spineboard. CONCLUSIONS IL1α and lactate both have a strong relationship with pressure exposure time, but not with pressure magnitude. Furthermore, IL1α was measured even in the absence of visible redness of the skin. The study offers the potention of biomarkers, reflecting inflammation and/or tissue metabolism, for use in assessing the effects of prolonged spineboard support.
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Skeletal muscle adaptation to immobilization and subsequent retraining in elderly men: No effect of anti-inflammatory medication.
Dideriksen, K, Boesen, AP, Kristiansen, JF, Magnusson, SP, Schjerling, P, Holm, L, Kjaer, M
Experimental gerontology. 2016;:8-18
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) may enhance resistance training induced gain in skeletal muscle mass and strength, but it is unknown if NSAIDs affects muscle loss during periods of inactivity in elderly individuals. Thus, we studied the influence of NSAID treatment on human skeletal muscle during immobilization and rehabilitation resistance training (retraining). METHODS 19 men (60-80yrs, range) were randomly assigned to ibuprofen (1200mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2weeks and retrained for 6weeks. Moreover, whey protein isolate was ingested (2×20g/d) throughout the whole study period. Plasma inflammatory markers, quadriceps muscle mass and strength, and muscle gene expression were investigated. RESULTS Muscle mass and strength decreased after 2weeks of immobilization (P<0.001), but returned to baseline levels after 2weeks of retraining combined with whey protein supplementation (P<0.001). Furthermore, muscle mass and strength reached beyond baseline levels after 6weeks of retraining (p<0.05), and NSAID did not significantly affect this (p>0.05). No group-differences, but differences over time, were observed for muscle gene expression of proteolytic and anabolic factors. Plasma inflammatory markers were unaffected by the study intervention and NSAID treatment. CONCLUSION Two weeks of lower limb immobilization lead to a reduction in muscle mass and strength, but these parameters were restored already after2 weeks of retraining and whey protein supplementation. After 6weeks of retraining and whey protein supplementation, muscle mass and strength increased beyond baseline levels, and NSAID treatment did not significantly influence this in elderly.
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Topical olive oil is not inferior to hyperoxygenated fatty aids to prevent pressure ulcers in high-risk immobilised patients in home care. Results of a multicentre randomised triple-blind controlled non-inferiority trial.
Lupiañez-Perez, I, Uttumchandani, SK, Morilla-Herrera, JC, Martin-Santos, FJ, Fernandez-Gallego, MC, Navarro-Moya, FJ, Lupiañez-Perez, Y, Contreras-Fernandez, E, Morales-Asencio, JM
PloS one. 2015;(4):e0122238
Abstract
UNLABELLED Pressure ulcers represent a major current health problem and produce an important economic impact on the healthcare system. Most of studies to prevent pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids and to date, no studies have specifically examined the use of olive oil-based substances. METHODS AND DESIGN Main objective: To assess the effectiveness of the use of olive oil, comparing it with hyperoxygenated fatty acids, for immobilised home-care patients at risk of suffering pressure ulcers. Design: Non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Scope: Population attending Primary Healthcare Centres in Andalusia (Spain). Sample: 831 immobilised patients at risk of suffering pressure ulcers. RESULTS The follow-up period was 16 weeks. Groups were similar after randomization. In the per protocol analysis, none of the body areas evaluated presented risk differences for pressure ulcers incidence that exceeded the 10% delta value established. Sacrum: Olive Oil 8 (2.55%) vs HOFA 8 (3.08%), ARR 0.53 (-2.2 to 3.26) Right heel: Olive Oil 4 (1.27%) vs HOFA 5 (1.92)%, ARR0.65 (-1.43 to 2.73). Left heel: Olive Oil 3 (0.96%) vs HOFA 3 (1.15%), ARR0.2 (-1.49 to 1.88). Right trochanter: Olive Oil 0 (0%) vs HOFA 4 (1.54%), ARR1.54 (0.04 to 3.03). Left trochanter: Olive Oil 1 (0.32%) vs HOFA 1 (0.38%), ARR0.07 (-0.91 to 1.04). In the intention to treat analysis the lower limit of the established confidence interval was never exceeded. DISCUSSION The results obtained confirmed that the use of topical extra-virgin olive oil to prevent PU in the home environment, for immobilised patients at high risk, is not inferior to the use of HOFA. Further studies are needed to investigate the mechanism by which olive oil achieves this outcome. TRIAL REGISTRATION Clinicaltrials.gov NCT01595347.
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Collagen Type III and VI Turnover in Response to Long-Term Immobilization.
Sun, S, Henriksen, K, Karsdal, MA, Byrjalsen, I, Rittweger, J, Armbrecht, G, Belavy, DL, Felsenberg, D, Nedergaard, AF
PloS one. 2015;(12):e0144525
Abstract
BACKGROUND Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. METHODS In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. RESULTS Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. CONCLUSION The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.
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Aging muscles and joints: mobilization.
Lach, HW, Lorenz, RA, L'Ecuyer, KM
Critical care nursing clinics of North America. 2014;(1):105-13
Abstract
Critical illness can impose immobility in older patients, resulting in loss of strength and functional ability. Many factors contribute to immobility, including patients' medical conditions, medical devices and equipment, nutrition, use of restraint, and staff priorities. Early mobilization reduces the impact of immobility and improves outcomes for older patients. Several important components make up successful mobility programs, including good patient assessment, a core set of interventions, and use of the interprofessional health care team. Nurses can lead in improving the mobilization of older critical care patients, thus reducing clinical risk in this vulnerable population.