scholarly journals Substantial and Reproducible Individual Variability in Skeletal Muscle Outcomes in the Cross-Over Designed Planica Bed Rest Program

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodrigo Fernandez-Gonzalo ◽  
Adam C. McDonnell ◽  
Elizabeth J. Simpson ◽  
Ian A. Macdonald ◽  
Eric Rullman ◽  
...  

To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SDExp2–SDCon2), where SDExp and SDCon are the standard deviations of the change score (i.e., post – pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to −17% for knee extension torque, −2 to −12% for calf muscle area, and −1 to −8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65–0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between −0.5 and −0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations.

Author(s):  
Desy Salvadego ◽  
Bruno Grassi ◽  
Michail E. Keramidas ◽  
Ola Eiken ◽  
Adam C. McDonnell ◽  
...  

This retrospective study was designed to analyse the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests, and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O2 uptake and muscle fractional O2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O2 uptake (SD: 4.1 and 3.3% after 10 days; 4.5 and 8.1% after 21 days, respectively) and peak muscle fractional O2 extraction (SD: 5.9 and 7.3% after 10 days; 6.5 and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related (r=0.66, P=0.004 after N-BR; r=0.61, P=0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0 and 15.7% after 10 and 21 days) and H-BR (SD: 13.0 and 19.8% after 10 and 21 days), no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after short and medium-term exposures.


1988 ◽  
Vol 16 (6) ◽  
pp. 624-629 ◽  
Author(s):  
Adrian LeBlanc ◽  
Prem Gogia ◽  
Victor Schneider ◽  
Jean Krebs ◽  
Ernesto Schonfeld ◽  
...  
Keyword(s):  
Bed Rest ◽  

2011 ◽  
Vol 111 (6) ◽  
pp. 1719-1726 ◽  
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Mauro Marzorati ◽  
Simone Porcelli ◽  
Enrico Rejc ◽  
...  

A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O2 extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered “peak”. Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O2 uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min−1·100 g−1). Skeletal muscle peak fractional O2 extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O2 delivery, a decrease in peak O2 uptake and muscle peak capacity of fractional O2 extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, “downstream” with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O2 utilization inside the muscle, peripheral O2 diffusion, and intracellular oxidative metabolism.


2020 ◽  
pp. 1-8
Author(s):  
K. Tsukasaki ◽  
Y. Matsui ◽  
H. Arai ◽  
A. Harada ◽  
M. Tomida ◽  
...  

Background: Muscle mass is often mentioned not to reflect muscle strength. For muscle mass assessment skeletal muscle index (SMI) is often used. We have reported that dual-energy X-ray absorptiometry (DXA)-derived SMI does not change with age in women, whereas the cross-sectional muscle area (CSMA) derived from computed tomography (CT) does. Objectives: The present study aimed to compare CT and DXA for the assessment of muscle tissue. Design & Setting: Cross-sectional study in the local residents. Participants: A total of 1818 subjects (age 40-89 years) randomly selected from community dwellers underwent CT examination of the right mid-thigh to measure the cross-sectional muscle area (CSMA). Skeletal muscle mass (SMM) was measured by DXA. The subjects performed physical function tests such as grip strength, knee extension strength, leg extension strength, and gait speed. The correlation between CT-derived CSMA and DXA-derived SMM along with their association with physical function was examined. Results: After controlling for related factors, the partial correlation coefficient of muscle cross-sectional area (CSA) with physical function was larger than that of DXA-derived SMM for gait speed in men (p=0.002) and knee extension strength in women (p=0.03). The partial correlation coefficient of quadriceps (Qc) CSA with physical function was larger than that of DXA-derived SMM for leg extension power in both sexes (p=0.01), gait speed in men (p<0.001), and knee extension strength in women (p<0.001). Conclusion: Mid-thigh CT-derived CSMA, especially Qc CSA, showed significant associations with grip strength, knee extension strength, and leg extension power, which were equal to or stronger than those of DXA-derived SMM in community-dwelling middle-aged and older Japanese people. The mid-thigh CSMA may be a predictor of mobility disability, and is considered to be useful in the diagnosis of sarcopenia.


2001 ◽  
Vol 3 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Maria Schaufelberger ◽  
Bengt O. Eriksson ◽  
Lars Lönn ◽  
Bengt Rundqvist ◽  
Katharina Stibrant Sunnerhagen ◽  
...  

2017 ◽  
Vol 20 (2) ◽  
pp. 119-131 ◽  
Author(s):  
Elina Sillanpää ◽  
Paula Niskala ◽  
Eija K. Laakkonen ◽  
Elodie Ponsot ◽  
Markku Alén ◽  
...  

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r= 0.69,p= .020) and in mean (r= 0.74,p= .014) and minimum SMTL (r= 0.88,p= .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r2= 0.30,p= .030), percentage total body (r2= 0.43,p= .014), and thigh (r2= 0.55,p= .004) fat, while minimum SMTL was associated with fat-free mass (r2= 0.27,p= .020) and thigh muscle area (r2= 0.42,p= .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.


2006 ◽  
Vol 52 (10) ◽  
pp. 1952-1957 ◽  
Author(s):  
Claudia Marsik ◽  
Raute Sunder-Plassmann ◽  
Bernd Jilma ◽  
Florian M Kovar ◽  
Christine Mannhalter ◽  
...  

Abstract Background: C-reactive protein (CRP) plays a major role in the immune system and is an independent risk marker of cardiovascular disease. However, CRP’s role in atherogenesis as innocent bystander, causative, or even protective agent, remains unresolved. The +1444C/T alteration in the CRP gene has been reported to determine basal CRP concentrations. We hypothesized that this alteration may also be associated with the degree of inflammatory response and coagulation activation in a well-standardized model of systemic inflammation. Methods: We administered 2 ng/kg endotoxin [Escherichia coli bacterial lipopolysaccharide (LPS)] intravenously to stimulate inflammation in 91 healthy young Caucasian male paid volunteers (age range, 19–40 years). Participants were confined to bed rest and fasted for 8.5 h after LPS infusion. We collected blood samples before LPS infusion and at 0, 2, 6, and 24 h after LPS infusion to measure inflammation markers [interleukin 6 (IL6), tumor necrosis factor-α (TNFα)], temperature, and coagulation markers (prothrombin fragment F1+2, D-dimer). We analyzed the CRP 3′ untranslated variant with a mutagenic separated PCR assay. Results: Basal concentrations of high-sensitivity CRP were ∼40% lower in +1444CC alteration carriers than in T homozygous (TT) allele carriers (P = 0.04). In contrast, basal IL6 concentrations were 2-fold higher in wild-type C homozygous (CC) than in TT individuals (P = 0.01). In response to the LPS challenge, CC individuals had 4-fold higher peak TNFα concentrations (P &lt;0.01), &gt;2.5-fold higher peak IL6 concentrations (P &lt;0.01), and increased temperature (P &lt;0.01). Twenty-four hours after LPS challenge, prothrombin fragment F1+2 concentrations were 75% higher and D-dimer concentrations 50% higher in CC than in TT individuals (P &lt;0.05). Conclusions: Genetic factors regulating CRP concentrations also modulate the individual response to endotoxin-stimulated inflammation.


2010 ◽  
Vol 42 ◽  
pp. 513
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Mauro Marzorati ◽  
Simone Porcelli ◽  
Enrico Rejc ◽  
...  

2020 ◽  
Author(s):  
Tomoyo Miyakuni ◽  
Hidenori Komiyama ◽  
Masamichi Takano ◽  
Takeshi Ikeda ◽  
Masato Matsushita ◽  
...  

Abstract Background: Peripheral artery disease (PAD), intermittent claudication, and impaired mobility lower patients’ quality of life, contributing to the loss of skeletal muscle. This study sought to investigate the impact of endovascular treatment (EVT) by measuring the mid-thigh level of muscle volume in above the knee PAD patients before and after EVT.Methods: In this prospective, observational study, symptomatic PAD patients with above the knee lesions who had intermittent claudication and were undergoing optimal medical treatment were enrolled. The mid-thigh level of muscle area was measured by computed tomography initially, and then 3 and 6 months after EVT. Patients were categorized into ipsilateral or bilateral based on clinical symptoms and initial ABI value. The muscle area in ischemic and non-ischemic legs were compared in ipsilateral PAD patients. The correlations between alterations in the total thigh muscle area and clinical characteristics were analyzed in univariable and multivariable analysis to investigate the factor contributing skeletal muscle loss.Results: A total of 22 patients were analyzed. The muscle area of the thighs increased after EVT. Fourteen patients had ipsilateral lesions and 8 had bilateral stenosis. In patients with ipsilateral lesions, the mid-thigh muscle area of ischemic lower limbs was significantly lesser than that of non-ischemic lower limbs (118.2±16.5 cm2 vs 124.0±17.3 cm2, p=0.0002). The thigh muscle area of ischemic lower limbs increased after EVT (before: 118.2±16.5 cm2 vs 3 months: 124.0±18.7 cm2, p=0.0166; before vs 6 months: 123.0±17.7 cm2, p= 0.0566), but this was not the case for non-ischemic lower limbs. Multivariate regression analysis revealed that baseline glycated hemoglobin was the only factor that negatively correlated with the change in the muscle area after 3 (β= -3.74, 95% confidence interval [CI] = -7.3 to -0.2, p=0.0417) and 6 months (β= -5.24, 95%CI = -10.1 to -0.4, p=0.03567). Muscle area significantly increased in normoglycemic HbA1c < 6.5 patients (before: 246.1±33.5 cm2, before vs 3 months: 249.6±34.6 cm2, p = 0.032, before vs 6 months: 250.6±35.7 cm2, p = 0.0455) while there was no significant alternation in hyperglycemic (HbA1c ≥ 6.5) patients (before: 225.2±43.4 cm2, 3 months: 224.6±44.8 cm2, 6 months: 222.2±45.5 cm2).Conclusions: Ischemia induces muscle atrophy in PAD patients. However, ischemic muscle atrophy was ameliorated after EVT in normoglycemic patients. There is a need for large scale trial to investigate the impact of EVT if it would protect or even delay skeletal muscle loss in all-comer population.


2003 ◽  
Vol 95 (5) ◽  
pp. 1851-1860 ◽  
Author(s):  
Fulvio Lauretani ◽  
Cosimo Roberto Russo ◽  
Stefania Bandinelli ◽  
Benedetta Bartali ◽  
Chiara Cavazzini ◽  
...  

Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study.


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