Heterogeneity of human adaptations to bed rest and hypoxia: a retrospective analysis within the skeletal muscle oxidative function

2021 ◽  
Author(s):  
Desy Salvadego ◽  
Bruno Grassi ◽  
Michail E. Keramidas ◽  
Ola Eiken ◽  
Adam C. McDonnell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Respiration ◽  
Bed Rest ◽  
Knee Extension ◽  
Large Variability ◽  
The Individual ◽  
Oxidative Function ◽  
Knee Extension Exercise ◽  
Permeabilized Muscle

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.

Mitochondrial respiration in creatine-loaded muscle: is there 31P-MRS evidence of direct effects of phosphocreatine and creatine in vivo?

2006 ◽  
Vol 100 (4) ◽  
pp. 1428-1430 ◽  
Author(s):  
Graham Kemp
Keyword(s):  
Respiration Rate ◽  
Mitochondrial Respiration ◽  
Strong Relationship ◽  
Knee Extension ◽  
Resonance Spectroscopy ◽  
Direct Effects ◽  
The Relationship ◽  
Knee Extension Exercise ◽  
Moderate Relationship

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using 31P-magnetic resonance spectroscopy in 16 men and women (36.9 ± 4.6 yr). The initial PCr resynthesis rate and time constant (Tc) were used as indicators of mitochondrial respiration after brief (10–12 s) and exhaustive (1–4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr ( r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP ( r = 0.77, P < 0.001), and no relationship with end-exercise pH ( r = −0.14, P = 0.34). The PCr Tc was not as strongly related to PCr, Cr, PCr/Cr, and ADP ( r < 0.77, P < 0.001–0.18) and was significantly influenced by end-exercise pH ( r = −0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr Tc.

Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion

2004 ◽  
Vol 96 (6) ◽  
pp. 2288-2292 ◽  
Author(s):  
Sinclair A. Smith ◽  
Scott J. Montain ◽  
Gary P. Zientara ◽  
Roger A. Fielding
Keyword(s):  
Respiration Rate ◽  
Mitochondrial Respiration ◽  
Strong Relationship ◽  
Knee Extension ◽  
Regulatory Mechanisms ◽  
Resonance Spectroscopy ◽  
The Relationship ◽  
Knee Extension Exercise ◽  
Moderate Relationship

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using 31P-magnetic resonance spectroscopy in 16 men and women (36.9 ± 4.6 yr). The initial PCr resynthesis rate and time constant (Tc) were used as indicators of mitochondrial respiration after brief (10–12 s) and exhaustive (1–4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr ( r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP ( r = 0.77, P < 0.001), and no relationship with end-exercise pH ( r = -0.14, P = 0.34). The PCr Tc was not as strongly related to PCr, Cr, PCr/Cr, and ADP ( r < 0.77, P < 0.001–0.18) and was significantly influenced by end-exercise pH ( r = -0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr Tc.

Hindlimb Muscle Dissection, Permeabilization, and Respirometry v1

2021 ◽  
Author(s):  
Matthew D. Campbell ◽  
David J. Marcinek
Keyword(s):  
Skeletal Muscle ◽  
Muscle Biopsy ◽  
Mitochondrial Respiration ◽  
Gastrocnemius Muscle ◽  
Muscle Fibers ◽  
Mouse Muscle ◽  
Skeletal Muscle Biopsy ◽  
Cellular Environment ◽  
Permeabilized Muscle

The use of permeabilized muscle fibers (PMF) has emerged as a gold standard for assessing skeletal muscle mitochondrial function. PMF provide an intermediate approach between in vivo strategies and isolated mitochondria that allows the mitochondria to be maintained in close to their native morphology in the myofiber while allowing greater control of substrate and inhibitor concentrations. However, like mitochondrial isolation, the primary drawback to PMF is disruption of the cellular environment during the muscle biopsy and preparation. Despite all the benefits of permeabilized muscle fibers in evaluating mitochondrial respiration and dynamics one of the major drawbacks is increased variability introduced during a muscle biopsy as well as intrinsic variation that exists due to sex and age. This study was designed to evaluate how age, sex, and biopsy preparations affect mitochondrial respiration in extensor digitorum longus, soleus, and gastrocnemius muscle of mice. Here we detail a modified approach to skeletal muscle biopsy of the gastrocnemius muscle of mice focused on maintenance of intact fibers that results in greater overall respiration compared to cut fibers. The improved respiration of intact fibers is sex specific as are some of the changes in mitochondrial respiration with age. This study shows the need for standard practices when measuring mitochondrial respiration in permeabilized muscle and provides a protocol to control for variation introduced during a typical mouse muscle biopsy.

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 ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bed Rest ◽  
Knee Extension ◽  
Individual Variability ◽  
Calf Muscle ◽  
Thigh Muscle ◽  
Individual Response ◽  
Muscle Area ◽  
Baseline Values ◽  
The Individual

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 &lt; 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P &lt; 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.

Impairment of Skeletal Muscle Oxidative Metabolism During Knee-Extension Exercise after Bed Rest

2010 ◽  
Vol 42 ◽  
pp. 513
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Mauro Marzorati ◽  
Simone Porcelli ◽  
Enrico Rejc ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Metabolism ◽  
Bed Rest ◽  
Knee Extension ◽  
Knee Extension Exercise

scholarly journals Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans

2016 ◽  
Vol 121 (1) ◽  
pp. 154-163 ◽  
Author(s):  
Desy Salvadego ◽  
Michail E. Keramidas ◽  
Lorenza Brocca ◽  
Rossana Domenis ◽  
Irene Mavelli ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Combined Effects ◽  
Oxidative Function

scholarly journals Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial V̇o2 during exercise

2012 ◽  
Vol 303 (1) ◽  
pp. R94-R100 ◽  
Author(s):  
Robert Boushel ◽  
Teresa Fuentes ◽  
Ylva Hellsten ◽  
Bengt Saltin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Knee Extension ◽  
Physiological Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome- c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG synthesis blockade (l-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of NG-monomethyl-l-arginine (l-NMMA; n = 4) and Indo ( n = 4) followed by combined inhibition of NOS and PG synthesis (l-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) with substrates for complex I (glutamate, malate) was reduced 50% by Indo. State 3 O2 flux with complex I and II substrates was reduced less with both Indo (20%) and l-NMMA + Indo (15%) compared with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by l-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O2 consumption during combined blockade of NOS and PG synthesis.

scholarly journals PlanHab* : hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone

2018 ◽  
Vol 596 (15) ◽  
pp. 3341-3355 ◽  
Author(s):  
Desy Salvadego ◽  
Michail E. Keramidas ◽  
Roger Kölegård ◽  
Lorenza Brocca ◽  
Stefano Lazzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bed Rest ◽  
Oxidative Function

scholarly journals Physiological and histological changes in skeletal muscle following in vivo gene transfer by electroporation

2011 ◽  
Vol 301 (5) ◽  
pp. C1239-C1250 ◽  
Author(s):  
Joseph A. Roche ◽  
Diana L. Ford-Speelman ◽  
Lisa W. Ru ◽  
Allison L. Densmore ◽  
Renuka Roche ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Green Fluorescent Protein ◽  
Intramuscular Injection ◽  
Fluorescent Protein ◽  
Contractile Function ◽  
Complete Recovery ◽  
Secondary Damage ◽  
The Individual ◽  
Green Fluorescent

Electroporation (EP) is used to transfect skeletal muscle fibers in vivo, but its effects on the structure and function of skeletal muscle tissue have not yet been documented in detail. We studied the changes in contractile function and histology after EP and the influence of the individual steps involved to determine the mechanism of recovery, the extent of myofiber damage, and the efficiency of expression of a green fluorescent protein (GFP) transgene in the tibialis anterior (TA) muscle of adult male C57Bl/6J mice. Immediately after EP, contractile torque decreased by ∼80% from pre-EP levels. Within 3 h, torque recovered to ∼50% but stayed low until day 3. Functional recovery progressed slowly and was complete at day 28. In muscles that were depleted of satellite cells by X-irradiation, torque remained low after day 3, suggesting that myogenesis is necessary for complete recovery. In unirradiated muscle, myogenic activity after EP was confirmed by an increase in fibers with central nuclei or developmental myosin. Damage after EP was confirmed by the presence of necrotic myofibers infiltrated by CD68+ macrophages, which persisted in electroporated muscle for 42 days. Expression of GFP was detected at day 3 after EP and peaked on day 7, with ∼25% of fibers transfected. The number of fibers expressing green fluorescent protein (GFP), the distribution of GFP+ fibers, and the intensity of fluorescence in GFP+ fibers were highly variable. After intramuscular injection alone, or application of the electroporating current without injection, torque decreased by ∼20% and ∼70%, respectively, but secondary damage at D3 and later was minimal. We conclude that EP of murine TA muscles produces variable and modest levels of transgene expression, causes myofiber damage due to the interaction of intramuscular injection with the permeabilizing current, and that full recovery requires myogenesis.

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