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VILMEN Christophe

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Key Words
- Small animal probe RMN
- Human and small animal electronics systems

Current Research Interest and projects



Journal Article

  • Chatel, B, Messonnier, LA, Barge, Q, Vilmen, C, Noirez, P, Bernard, M, Pialoux, V & Bendahan, D 2018, “Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease”, Molecular Genetics and Metabolism, vol. 123, no. 3, p. 400-410.
    Résumé : Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n=10), HbAS (HbAS-END, n=11) and HbSS (HbSS-END, n=8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest - exercise - recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p<0.001) and intense (p<0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p<0.001) and HbAS-END (p<0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p<0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.
    Mots-clés : crmbm, msk, Muscle energetics, Muscle force production, pH, Physical activity.

  • Fouré, A, Ogier, AC, Le Troter, A, Vilmen, C, Feiweier, T, Guye, M, Gondin, J, Besson, P & Bendahan, D 2018, “Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography: Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability”, Radiology, vol. 287, no. 2, p. 592-607.
    Résumé : Purpose To demonstrate the reproducibility of the diffusion properties and three-dimensional structural organization measurements of the lower leg muscles by using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0-T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On the basis of robust statistical mapping analyses, this study also aimed at determining the sensitivity of the measurements to sex difference and intramuscular variability. Materials and Methods All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Reproducibility of diffusion tensor indexes assessment including eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle volume and architecture (ie, fiber length and pennation angle) were characterized in lower leg muscles (n = 8). Intramuscular variability and sex differences were characterized in young healthy men and women (n = 10 in each group). Student t test, statistical parametric mapping, correlation coefficients (Spearman rho and Pearson product-moment) and coefficient of variation (CV) were used for statistical data analysis. Results High reproducibility of measurements (mean CV ± standard deviation, 4.6% ± 3.8) was determined in diffusion properties and architectural parameters. Significant sex differences were detected in FA (4.2% in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for the entire lower leg; P = .008), whereas architecture parameters were almost identical across sex. Additional differences were found independently of sex in diffusion properties and architecture along several muscles of the lower leg. Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows a reproducible assessment of structural organization of superficial and deep muscles, giving indirect information on muscle function. ©RSNA, 2018 Online supplemental material is available for this article.
    Mots-clés : crmbm, msk.

  • Macia, M, Pecchi, E, Desrois, M, Lan, C, Vilmen, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2018, “Exercise training impacts exercise tolerance and bioenergetics in gastrocnemius muscle of non-obese type-2 diabetic Goto-Kakizaki rat in vivo”, Biochimie.
    Résumé : The functional and bioenergetics impact of regular physical activity upon type-2 diabetic skeletal muscle independently of confounding factors of overweight remains undocumented. Here, gastrocnemius muscle energy fluxes, mitochondrial capacity and mechanical performance were assessed noninvasively and longitudinally in non-obese diabetic Goto-Kakizaki rats using magnetic resonance (MR) imaging and dynamic 31-phosphorus MR spectroscopy (31P-MRS) throughout a 6-min fatiguing bout of exercise performed before, in the middle (4-week) and at the end of an 8-week training protocol consisting in 60-min daily run on a treadmill. The training protocol reduced plasmatic insulin level (-61%) whereas blood glucose and non-esterified fatty acids levels remained unaffected, thereby indicating an improvement of insulin sensitivity. It also increased muscle mitochondrial citrate synthase activity (+45%) but this increase did not enhance oxidative ATP synthesis capacity in working muscle in vivo while glycolytic ATP production was increased (+33%). On the other hand, the training protocol impaired maximal force-generating capacity (-9%), total amount of force produced (-12%) and increased ATP cost of contraction (+32%) during the fatiguing exercise. Importantly, these deleterious effects were transiently worsened in the middle of the 8-week period, in association with reduced oxidative capacity and increased basal [Pi]/[PCr] ratio (an in vivo biomarker of muscle damage). These data demonstrate that the beneficial effect of regular training on insulin sensitivity in non-obese diabetic rat occurs separately from any improvement in muscle mitochondrial function and might be linked to an increased capacity for metabolizing glucose through anaerobic process in exercising muscle.
    Mots-clés : crmbm, cvs, Diabetes, Mitochondrial capacity, msk, Nuclear magnetic resonance, Regular physical activity, Skeletal muscle function.


Journal Article

  • Chatel, B, Hourdé, C, Gondin, J, Fouré, A, Le Fur, Y, Vilmen, C, Bernard, M, Messonnier, LA & Bendahan, D 2017, “Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease”, Blood Cells, Molecules & Diseases, vol. 63, p. 37-44.
    Résumé : Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability. We showed that specific maximal tetanic force was lower in HbSS mice as compared to other groups. At the onset of the stimulation period, peak force was reduced in HbSS and HbAS mice as compared to HbAA mice. Contrary to the moderate protocol, the intense stimulation protocol was associated with a larger decrease in peak force and rate of force development in HbSS mice as compared to HbAA and HbAS mice. These findings provide in vivo evidence of impaired muscle force production and resistance to fatigue in SCD. These changes are independent of muscle mass. Moreover, SCD is associated with muscle fatigability when exercise intensity is high.
    Mots-clés : crmbm, Exercise intensity, msk, Muscle mass, Muscle volume, Rate of force development.

  • Fouré, A, Duhamel, G, Vilmen, C, Bendahan, D, Jubeau, M & Gondin, J 2017, “Fast measurement of the quadriceps femoris muscle transverse relaxation time at high magnetic field using segmented echo-planar imaging”, Journal of magnetic resonance imaging: JMRI, vol. 45, no. 2, p. 356-368.
    Résumé : PURPOSE: To assess and validate a technique for transverse relaxation time (T2 ) measurements of resting and recovering skeletal muscle following exercise with a high temporal resolution and large volume coverage using segmented spin-echo echo-planar imaging (sSE-EPI). MATERIALS AND METHODS: Experiments were performed on a 3T magnetic resonance imaging (MRI) scanner using a multislice sSE-EPI technique applied at different echo times (TEs). T2 measurements were first validated in vitro in calibrated T2 phantoms (range: 25-152 ms) by comparing sSE-EPI, standard spin-echo (SE), and multislice multiecho (MSME) techniques (using a fitting procedure or a 2-TEs calculation). In vivo measurements of resting T2 quadriceps femoris (QF) muscle were performed with both sSE-EPI and MSME sequences. Finally, sSE-EPI was used to quantify T2 changes in recovering muscle after an exercise. RESULTS: T2 values measured in vitro with sSE-EPI were similar to those assessed with SE (P > 0.05). In vitro and in vivo T2 measurements obtained with sSE-EPI were independent of the T2 determination procedure (P > 0.05). In contrast, both in vitro and in vivo T2 values derived from MSME were significantly different when using 2-TEs calculation as compared to the fitting procedure (P < 0.05). sSE-EPI allowed the detection of increased T2 values in the QF muscle immediately after exercise (+14 ± 9%), while lower T2 values were recorded less than 2 min afterwards (P < 0.05). CONCLUSION: sSE-EPI sequence is a relevant method to monitor exercise-induced T2 changes of skeletal muscles over large volume coverage and to detect abnormal patterns of muscle activation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:356-368.
    Mots-clés : crmbm, Exercise, MRI, msk, skeletal muscle, spin-echo sequence, T2.

  • Wegrzyk, J, Ranjeva, J-P, Fouré, A, Kavounoudias, A, Vilmen, C, Mattei, J-P, Guye, M, Maffiuletti, NA, Place, N, Bendahan, D & Gondin, J 2017, “Specific brain activation patterns associated with two neuromuscular electrical stimulation protocols”, Scientific Reports, vol. 7, no. 1, p. 2742.
    Résumé : The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements.
    Mots-clés : crmbm, msk.


Journal Article

  • Béchir, N, Pecchi, E, Vilmen, C, Le Fur, Y, Amthor, H, Bernard, M, Bendahan, D & Giannesini, B 2016, “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo”, FASEB journal: official publication of the Federation of American Societies for Experimental Biology, vol. 30, no. 10, p. 3551-3562.
    Résumé : Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [(31)P]-MR spectroscopy ([(31)P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
    Mots-clés : crmbm, Duchenne muscular dystrophy, msk, Muscle Fatigue, myostatin inhibition, skeletal muscle hypertrophy.

  • Fouré, A, Nosaka, K, Gastaldi, M, Mattei, J-P, Boudinet, H, Guye, M, Vilmen, C, Le Fur, Y, Bendahan, D & Gondin, J 2016, “Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial”, Clinical Nutrition (Edinburgh, Scotland), vol. 35, no. 1, p. 83-94.
    Résumé : BACKGROUND & AIMS: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. METHODS: (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. RESULTS: No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). CONCLUSIONS: The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage.
    Mots-clés : crmbm, Double blind randomized placebo controlled trial, Exercise induced-muscle damage, Magnetic Resonance Spectroscopy, msk.

  • Layec, G, Bringard, A, LE Fur, Y, Micallef, J-P, Vilmen, C, Perrey, S, Cozzone, PJ & Bendahan, D 2016, “Mitochondrial Coupling and Contractile Efficiency in Humans with High and Low V˙O2peaks”, Medicine and Science in Sports and Exercise, vol. 48, no. 5, p. 811-821.
    Résumé : INTRODUCTION: Endurance training elicits tremendous adaptations of the mitochondrial energetic capacity. Yet, the effects of training or physical fitness on mitochondrial efficiency during exercise are still unclear. Accordingly, the purpose of the present study was to examine in vivo the differences in mitochondrial efficiency and ATP cost of contraction during exercise in two groups of adults differing in their aerobic capacity. METHOD: We simultaneously assessed the ATP synthesis and O2 fluxes with P-magnetic resonance spectroscopy and pulmonary gas exchange measurements in seven endurance-trained (ET, V˙O2max: 67 ± 8 mL·min·kg) and seven recreationally active (RA, V˙O2max: 43 ± 7 mL·min·kg) subjects during 6 min of dynamic moderate-intensity knee extension. RESULTS: The ATP cost of dynamic contraction was not significantly different between ET and RA (P > 0.05). Similarly, end-exercise O2 consumption was not significantly different between groups (ET: 848 ± 155 mL·min and RA: 760 ± 131 mL·min, P > 0.05). During the recovery period, the PCr offset time constant was significantly faster in ET compared with RA (ET: 32 ± 8 s and RA: 43 ± 10 s, P < 0.05), thus indicating an increased mitochondrial capacity for ATP synthesis in the quadriceps of ET. In contrast, the estimated mitochondrial efficiency during exercise was not significantly different (P/O, ET: 2.0 ± 1.0 and RA: 1.8 ± 0.4, P > 0.05). Consequently, the higher mitochondrial capacity for ATP synthesis in ET likely originated from an elevated mitochondrial volume density, mitochondria-specific respiratory capacity, and/or slower postexercise inactivation of oxidative phosphorylation by the parallel activation mechanism. CONCLUSION: Together, these findings reveal that 1) mitochondrial and contractile efficiencies are unaltered by several years of endurance training in young adults, and 2) the training-induced improvement in mitochondrial energetic capacity appears to be independent from changes in mitochondrial coupling.
    Mots-clés : crmbm, msk.

  • Martin, A, Grosprêtre, S, Vilmen, C, Guye, M, Mattei, J-P, LE Fur, Y, Bendahan, D & Gondin, J 2016, “The Etiology of Muscle Fatigue Differs between Two Electrical Stimulation Protocols”, Medicine and Science in Sports and Exercise, vol. 48, no. 8, p. 1474-1484.
    Résumé : PURPOSE: This study aimed at investigating the mechanisms involved in the force reduction induced by two electrical stimulation (ES) protocols that were designed to activate motor units differently. METHODS: The triceps surae of 11 healthy subjects (8 men; age, ~28 yr) was activated using ES applied over the tibial nerve. Two ES protocols (conventional [CONV]: 20 Hz, 0.05 ms vs wide-pulse high-frequency [WPHF]: 80 Hz, 1 ms) were performed and involved 40 trains (6 s on-6 s off) delivered at an intensity (IES) evoking 20% of maximal voluntary contraction. To analyze the mechanical properties of the motor units activated at IES, force-frequency relation was evoked before and after each protocol. H-reflex and M-wave responses evoked by the last stimulation pulse were also assessed during each ES protocol. Electromyographic responses (∑EMG) were recorded after each train to analyze the behavior of the motor units activated at IES. Metabolic variables, including relative concentrations of phosphocreatine and inorganic phosphate as well as intracellular pH, were assessed using P-MR spectroscopy during each protocol. RESULTS: Larger H-reflex amplitudes were observed during WPHF as compared with CONV, whereas opposite findings were observed for M-wave amplitudes. Despite this difference, both the force reduction (-26%) and metabolic changes were similar between the two protocols. The CONV protocol induced a rightward shift of the force-frequency relation, whereas a significant reduction of the ∑EMG evoked at IES was observed only for the WPHF. CONCLUSIONS: These results suggest that a decreased number of active motor units mainly contributed to WPHF-induced force decrease, whereas intracellular processes were most likely involved in the force reduction occurring during CONV stimulation.
    Mots-clés : crmbm, msk.


Journal Article

  • Fouré, A, Wegrzyk, J, LE Fur, Y, Mattei, J-P, Boudinet, H, Vilmen, C, Bendahan, D & Gondin, J 2015, “Impaired mitochondrial function and reduced energy cost as a result of muscle damage”, Medicine and Science in Sports and Exercise, vol. 47, no. 6, p. 1135-1144.
    Résumé : PURPOSE: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remain to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise, but the magnitude of muscle energetics alterations for NMES EIMD has never been documented. METHODS: P magnetic resonance spectroscopy measurements were performed in 13 young healthy males during a standardized rest-exercise-recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec). RESULTS: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly owing to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%). CONCLUSION: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of noncontractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.
    Mots-clés : crmbm, msk.

  • Jubeau, M, LE Fur, Y, Duhamel, G, Wegrzyk, J, Confort-Gouny, S, Vilmen, C, Cozzone, PJ, Mattei, JP, Bendahan, D & Gondin, J 2015, “Localized metabolic and t2 changes induced by voluntary and evoked contractions”, Medicine and Science in Sports and Exercise, vol. 47, no. 5, p. 921-930.
    Résumé : PURPOSE: This study compared the metabolic and activation changes induced by electrically evoked (neuromuscular electrical stimulation (NMES)) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations. METHODS: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3-T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi), and pH, were recorded using localized P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis and from the nondirectly stimulated rectus femoris/vastus intermedius muscles. RESULTS: PCr depletion recorded throughout the NMES session was significantly larger in the vastus lateralis as compared with the rectus femoris/vastus intermedius muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared with VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared with VOL for both muscles but were not necessarily related to the localized metabolic demand. CONCLUSION: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels.
    Mots-clés : crmbm, msk.

  • Layec, G, Bringard, A, Le Fur, Y, Micallef, J-P, Vilmen, C, Perrey, S, Cozzone, PJ & Bendahan, D 2015, “Opposite effects of hyperoxia on mitochondrial and contractile efficiency in human quadriceps muscles”, American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 308, no. 8, p. R724-733.
    Résumé : Exercise efficiency is an important determinant of exercise capacity. However, little is known about the physiological factors that can modulate muscle efficiency during exercise. We examined whether improved O2 availability would 1) impair mitochondrial efficiency and shift the energy production toward aerobic ATP synthesis and 2) reduce the ATP cost of dynamic contraction owing to an improved neuromuscular efficiency, such that 3) whole body O2 cost would remain unchanged. We used (31)P-magnetic resonance spectroscopy, surface electromyography, and pulmonary O2 consumption (V̇o2p) measurements in eight active subjects during 6 min of dynamic knee-extension exercise under different fractions of inspired O2 (FiO2 , 0.21 in normoxia and 1.0 in hyperoxia). V̇o2p (755 ± 111 ml/min in normoxia and 799 ± 188 ml/min in hyperoxia, P > 0.05) and O2 cost (P > 0.05) were not significantly different between normoxia and hyperoxia. In contrast, the total ATP synthesis rate and the ATP cost of dynamic contraction were significantly lower in hyperoxia than normoxia (P < 0.05). As a result, the ratio of the rate of oxidative ATP synthesis from the quadriceps to V̇o2p was lower in hyperoxia than normoxia but did not reach statistical significance (16 ± 3 mM/ml in normoxia and 12 ± 5 mM/ml in hyperoxia, P = 0.07). Together, these findings reveal dynamic and independent regulations of mitochondrial and contractile efficiency as a consequence of O2 availability in young active individuals. Furthermore, muscle efficiency appears to be already optimized in normoxia and is unlikely to contribute to the well-established improvement in exercise capacity induced by hyperoxia.
    Mots-clés : 31P-magnetic resonance spectroscopy, Adenosine Triphosphate, Adult, Bicycling, crmbm, Electromyography, Energy Metabolism, Exercise, Exercise Tolerance, Female, Humans, Hydrogen-Ion Concentration, Hyperoxia, Isometric Contraction, Lung, Magnetic Resonance Spectroscopy, Male, Mitochondria, Mitochondria, Muscle, msk, muscle efficiency, Muscle energetics, Muscle Fatigue, Muscle Strength, O2 availability, Oxygen Consumption, Quadriceps Muscle, Time Factors.

  • Macia, M, Pecchi, E, Vilmen, C, Desrois, M, Lan, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2015, “Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo”, PloS One, vol. 10, no. 6, p. e0129579.
    Résumé : Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM) development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK) rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA). Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator). During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz), mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.
    Mots-clés : crmbm, cvs, msk.

  • Wegrzyk, J, Fouré, A, Le Fur, Y, Maffiuletti, NA, Vilmen, C, Guye, M, Mattei, J-P, Place, N, Bendahan, D & Gondin, J 2015, “Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans”, PloS One, vol. 10, no. 11, p. e0143972.
    Résumé : Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.
    Mots-clés : crmbm, msk.
  • Wegrzyk, J, Foure, A, Vilmen, C, Ghattas, B, Maffiuletti, NA, Mattei, J-P, Place, N, Bendahan, D & Gondin, J 2015, “Extra Forces induced by wide-pulse, high-frequency electrical stimulation: Occurrence, magnitude, variability and underlying mechanisms”, Clinical Neurophysiology, vol. 126, no. 7, p. 1400-1412.
    Résumé : Objective: In contrast to conventional (CONV) neuromuscular electrical stimulation (NMES), the use of "wide-pulse, high-frequencies" (WPHF) can generate higher forces than expected by the direct activation of motor axons alone. We aimed at investigating the occurrence, magnitude, variability and underlying neuromuscular mechanisms of these "Extra Forces" (EF). Methods: Electrically-evoked isometric plantar flexion force was recorded in 42 healthy subjects. Additionally, twitch potentiation, H-reflex and M-wave responses were assessed in 13 participants. CONV (25 Hz, 0.05 ms) and WPHF (100 Hz, 1 ms) NMES consisted of five stimulation trains (20 s on-90 s off). Results: K-means clustering analysis disclosed a responder rate of almost 60%. Within this group of responders, force significantly increased from 4% to 16% of the maximal voluntary contraction force and H-reflexes were depressed after WPHF NMES. In contrast, non-responders showed neither EF nor H-reflex depression. Twitch potentiation and resting EMG data were similar between groups. Interestingly, a large inter-and intrasubject variability of EF was observed. Conclusion: The responder percentage was overestimated in previous studies. Significance: This study proposes a novel methodological framework for unraveling the neurophysiological mechanisms involved in EF and provides further evidence for a central contribution to EF in responders. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Mots-clés : Adult, Cluster Analysis, crmbm, Electric Stimulation, Electromyography, EMG, Evoked Potentials, Extra Forces, Female, H-Reflex, Humans, Male, msk, Muscle Contraction, Muscle Strength, Muscle, Skeletal, NMES, NMES, Extra Forces, Triceps surae, Responder, EMG, plateau-like behavior, spinal-cord-injury, post-activation depression, human skeletal-muscle, catch-like property, soleus h-reflex, neuromuscular stimulation, triceps surae, m-waves, presynaptic inhibition, Responder, Single-Blind Method, Triceps surae.

  • Yashiro, K, Tonson, A, Pecchi, É, Vilmen, C, Le Fur, Y, Bernard, M, Bendahan, D & Giannesini, B 2015, “Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo”, PloS One, vol. 10, no. 6, p. e0128016.
    Résumé : Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.
    Mots-clés : crmbm, cvs.


Journal Article

  • Fouré, A, Nosaka, K, Wegrzyk, J, Duhamel, G, Le Troter, A, Boudinet, H, Mattei, J-P, Vilmen, C, Jubeau, M, Bendahan, D & Gondin, J 2014, “Time course of central and peripheral alterations after isometric neuromuscular electrical stimulation-induced muscle damage”, PloS One, vol. 9, no. 9, p. e107298.
    Résumé : Isometric contractions induced by neuromuscular electrostimulation (NMES) have been shown to result in a prolonged force decrease but the time course of the potential central and peripheral factors have never been investigated. This study examined the specific time course of central and peripheral factors after isometric NMES-induced muscle damage. Twenty-five young healthy men were subjected to an NMES exercise consisting of 40 contractions for both legs. Changes in maximal voluntary contraction force of the knee extensors (MVC), peak evoked force during double stimulations at 10 Hz (Db10) and 100 Hz (Db100), its ratio (10∶100), voluntary activation, muscle soreness and plasma creatine kinase activity were assessed before, immediately after and throughout four days after NMES session. Changes in knee extensors volume and T2 relaxation time were also assessed at two (D2) and four (D4) days post-exercise. MVC decreased by 29% immediately after NMES session and was still 19% lower than the baseline value at D4. The decrease in Db10 was higher than in Db100 immediately and one day post-exercise resulting in a decrease (-12%) in the 10∶100 ratio. On the contrary, voluntary activation significantly decreased at D2 (-5%) and was still depressed at D4 (-5%). Muscle soreness and plasma creatine kinase activity increased after NMES and peaked at D2 and D4, respectively. T2 was also increased at D2 (6%) and D4 (9%). Additionally, changes in MVC and peripheral factors (e.g., Db100) were correlated on the full recovery period, while a significant correlation was found between changes in MVC and VA only from D2 to D4. The decrease in MVC recorded immediately after the NMES session was mainly due to peripheral changes while both central and peripheral contributions were involved in the prolonged force reduction. Interestingly, the chronological events differ from what has been reported so far for voluntary exercise-induced muscle damage.
    Mots-clés : Adult, crmbm, Electric Stimulation, Electromyography, Exercise, Humans, Isometric Contraction, Knee, Male, Muscle Contraction, Muscle Fatigue, Neuromuscular Diseases.

  • Gineste, C, Ottenheijm, C, Le Fur, Y, Banzet, S, Pecchi, E, Vilmen, C, Cozzone, PJ, Koulmann, N, Hardeman, EC, Bendahan, D & Gondin, J 2014, “Alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of nemaline myopathy”, PloS One, vol. 9, no. 9, p. e109066.
    Résumé : Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8-9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.
    Mots-clés : crmbm.

  • Gondin, J, Vilmen, C, Cozzone, PJ, Bendahan, D & Duhamel, G 2014, “High-field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non-invasive combined stimulation and force measurement device”, NMR in biomedicine, vol. 27, no. 8, p. 870-879.
    Résumé : We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2 -weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high-field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions.
    Mots-clés : crmbm.

  • Kazuya, Y, Tonson, A, Pecchi, E, Dalmasso, C, Vilmen, C, Fur, YL, Bernard, M, Bendahan, D & Giannesini, B 2014, “A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle”, American Journal of Physiology. Endocrinology and Metabolism, vol. 306, no. 10, p. E1110-1119.
    Résumé : Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.
    Mots-clés : Animals, Biomechanical Phenomena, Capsaicin, Cells, Cultured, crmbm, Electric Stimulation, Energy Metabolism, Male, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Physical Conditioning, Animal.
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Journal Article

  • Giannesini, B, Vilmen, C, Amthor, H, Bernard, M & Bendahan, D 2013, “Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo”, American journal of physiology. Endocrinology and metabolism, vol. 305, no. 1, p. E33-40.
    Résumé : Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.
    Mots-clés : Adenosine Triphosphate, Animals, Biomechanics, crmbm, Electric Stimulation, Energy Metabolism, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Contraction, Muscle, Skeletal, Muscular Atrophy, Myostatin, Physical Conditioning, Animal.

  • Gineste, C, De Winter, JM, Kohl, C, Witt, CC, Giannesini, B, Brohm, K, Le Fur, Y, Gretz, N, Vilmen, C, Pecchi, E, Jubeau, M, Cozzone, PJ, Stienen, GJM, Granzier, H, Labeit, S, Ottenheijm, CAC, Bendahan, D & Gondin, J 2013, “In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype”, Neuromuscular disorders: NMD, vol. 23, no. 4, p. 357-369.
    Résumé : Nemaline myopathy is the most common congenital skeletal muscle disease, and mutations in the nebulin gene account for 50% of all cases. Recent studies suggest that the disease severity might be related to the nebulin expression levels. Considering that mutations in the nebulin gene are typically recessive, one would expect that a single functional nebulin allele would maintain nebulin protein expression which would result in preserved skeletal muscle function. We investigated skeletal muscle function of heterozygous nebulin knock-out (i.e., nebulin(+/-)) mice using a multidisciplinary approach including protein and gene expression analysis and combined in vivo and in vitro force measurements. Skeletal muscle anatomy and energy metabolism were studied strictly non-invasively using magnetic resonance imaging and 31P-magnetic resonance spectroscopy. Maximal force production was reduced by around 16% in isolated muscle of nebulin(+/-) mice while in vivo force generating capacity was preserved. Muscle weakness was associated with a shift toward a slower proteomic phenotype, but was not related to nebulin protein deficiency or to an impaired energy metabolism. Further studies would be warranted in order to determine the mechanisms leading to a mild skeletal muscle phenotype resulting from the expression of a single nebulin allele.
    Mots-clés : Animals, crmbm, Disease Models, Animal, Gene Expression, Heterozygote, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Knockout, Muscle Proteins, Muscle Strength, Muscle Weakness, Muscle, Skeletal, Mutation, Myopathies, Nemaline, Phenotype, Severity of Illness Index.
    Note Note
    The following values have no corresponding Zotero field:<br />Author Address: Aix-Marseille Universite, CRMBM, 13005 Marseille, France; CNRS, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), 13005 Marseille, France.<br />C2 - Muscle <br />ET - 2013/02/05<br />
    Note Note
    <p>Gineste, C<br/>De Winter, J M<br/>Kohl, C<br/>Witt, C C<br/>Giannesini, B<br/>Brohm, K<br/>Le Fur, Y<br/>Gretz, N<br/>Vilmen, C<br/>Pecchi, E<br/>Jubeau, M<br/>Cozzone, P J<br/>Stienen, G J M<br/>Granzier, H<br/>Labeit, S<br/>Ottenheijm, C A C<br/>Bendahan, D<br/>Gondin, J<br/>England<br/>Neuromuscular disorders : NMD<br/>Neuromuscul Disord. 2013 Apr;23(4):357-69. doi: 10.1016/j.nmd.2012.12.011. Epub 2013 Feb 1.</p>

  • Gineste, C, Duhamel, G, Le Fur, Y, Vilmen, C, Cozzone, PJ, Nowak, KJ, Bendahan, D & Gondin, J 2013, “Multimodal MRI and (31)P-MRS Investigations of the ACTA1(Asp286Gly) Mouse Model of Nemaline Myopathy Provide Evidence of Impaired In Vivo Muscle Function, Altered Muscle Structure and Disturbed Energy Metabolism”, PloS one, vol. 8, no. 8, p. e72294.
    Résumé : Nemaline myopathy (NM), the most common non-dystrophic congenital disease of skeletal muscle, can be caused by mutations in the skeletal muscle α-actin gene (ACTA1) (~25% of all NM cases and up to 50% of severe forms of NM). Muscle function of the recently generated transgenic mouse model carrying the human Asp286Gly mutation in the ACTA1 gene (Tg(ACTA1)(Asp286Gly)) has been mainly investigated in vitro. Therefore, we aimed at providing a comprehensive picture of the in vivo hindlimb muscle function of Tg(ACTA1)(Asp286Gly) mice by combining strictly noninvasive investigations. Skeletal muscle anatomy (hindlimb muscles, intramuscular fat volumes) and microstructure were studied using multimodal magnetic resonance imaging (Dixon, T2, Diffusion Tensor Imaging [DTI]). Energy metabolism was studied using 31-phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (1-150 Hz) and a fatigue protocol (6 min-1.7 Hz). Tg(ACTA1)(Asp286Gly) mice showed a mild muscle weakness as illustrated by the reduction of both absolute (30%) and specific (15%) maximal force production. Dixon MRI did not show discernable fatty infiltration in Tg(ACTA1)(Asp286Gly) mice indicating that this mouse model does not reproduce human MRI findings. Increased T2 values were observed in Tg(ACTA1)(Asp286Gly) mice and might reflect the occurrence of muscle degeneration/regeneration process. Interestingly, T2 values were linearly related to muscle weakness. DTI experiments indicated lower λ2 and λ3 values in Tg(ACTA1)(Asp286Gly) mice, which might be associated to muscle atrophy and/or the presence of histological anomalies. Finally (31)P-MRS investigations illustrated an increased anaerobic energy cost of contraction in Tg(ACTA1)(Asp286Gly) mice, which might be ascribed to contractile and non-contractile processes. Overall, we provide a unique set of information about the anatomic, metabolic and functional consequences of the Asp286Gly mutation that might be considered as relevant biomarkers for monitoring the severity and/or the progression of NM and for assessing the efficacy of potential therapeutic interventions.
    Mots-clés : crmbm.

  • Gineste, C, Le Fur, Y, Vilmen, C, Le Troter, A, Pecchi, E, Cozzone, PJ, Hardeman, EC, Bendahan, D & Gondin, J 2013, “Combined MRI and (31)P-MRS Investigations of the ACTA1(H40Y) Mouse Model of Nemaline Myopathy Show Impaired Muscle Function and Altered Energy Metabolism”, PloS one, vol. 8, no. 4, p. e61517.
    Résumé : Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1) account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and (31)Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (-40%) and specific (-25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.
    Mots-clés : Actins, Animals, crmbm, Energy Metabolism, Female, Magnetic Resonance Imaging, Mice, Mice, Mutant Strains, Muscle, Skeletal, Myopathies, Nemaline.


Journal Article

  • Chiche, J, Le Fur, Y, Vilmen, C, Frassineti, F, Daniel, L, Halestrap, AP, Cozzone, PJ, Pouysségur, J & Lutz, NW 2012, “In vivo pH in metabolic-defective Ras-transformed fibroblast tumors: key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pH”, International journal of cancer. Journal international du cancer, vol. 130, no. 7, p. 1511-1520.
    Résumé : We present an investigation of tumor pH regulation, designed to support a new anticancer therapy concept that we had previously proposed. Our study uses a tumor model of ras-transformed hamster fibroblasts, CCL39, xenografted in the thighs of nude mice. We demonstrate, for the first time, that genetic modifications of specific mechanisms of proton production and/or proton transport result in distinct, reproducible changes in intracellular and extracellular tumor pH that can be detected and quantified noninvasively in vivo, simultaneously with determinations of tumor energetic status and necrosis in the same experiment. The CCL39 variants used were deficient in the sodium/proton exchanger, NHE-1, and/or in the monocarboxylate transporter, MCT4; further, variants were deficient in glycolysis or respiration. MCT4 expression markedly increased the gradient between intracellular and extracellular pH from 0.14 to 0.43 when compared to CCL39 wild-type tumors not expressing MCT4. The other genetic modifications studied produced smaller but significant increases in intracellular and decreases in extracellular pH. In general, increased pH gradients were paralleled by increased tumor growth performance and diminished necrotic regions, and 50% of the CCL39 variant expressing neither MCT4 nor NHE-1, but possessing full genetic capacity for glycolysis and oxidative phosphorylation, underwent regression before reaching a 1-cm diameter. Except for CCL39 wild-type tumors, no significant HIF-1α expression was detected. Our in vivo results support a multipronged approach to tumor treatment based on minimizing intracellular pH by targeting several proton production and proton transport processes, among which the very efficient MCT4 proton/lactate co-transport deserves particular attention.
    Mots-clés : Animals, Cell Line, Tumor, Cell Transformation, Neoplastic, Cricetinae, crmbm, Fibroblasts, Genes, ras, Glycolysis, Hydrogen-Ion Concentration, Hypoxia-Inducible Factor 1, alpha Subunit, Ion Exchange, Ion Transport, Mice, Mice, Nude, Monocarboxylic Acid Transporters, Muscle Proteins, Mutation, Necrosis, Oxidative Phosphorylation, Phospholipids, Protons, Sodium-Hydrogen Antiporter.

  • Layec, G, Bringard, A, Yashiro, K, Le Fur, Y, Vilmen, C, Micallef, J-P, Perrey, S, Cozzone, PJ & Bendahan, D 2012, “The slow components of phosphocreatine and pulmonary oxygen uptake can be dissociated during heavy exercise according to training status”, Experimental physiology, vol. 97, no. 8, p. 955-969.
    Résumé : To better understand the mechanisms underlying the pulmonary O(2) uptake (V(O(2P))) slow component during high-intensity exercise, we used (31)P magnetic resonance spectroscopy, gas exchange, surface electromyography and near-infrared spectroscopy measurements to examine the potential relationship between the slow components of V(O(2P)) and phosphocreatine (PCr), muscle recruitment and tissue oxygenation in endurance-trained athletes and sedentary subjects. Specifically, six endurance-trained and seven sedentary subjects performed a dynamic high-intensity exercise protocol during 6 min at an exercise intensity corresponding to 35-40% of knee-extensor maximal voluntary contraction. The slow component of V(O(2P))(117 ± 60 ml min(-1), i.e. 20 ± 10% of the total response) was associated with a paradoxical PCr resynthesis in endurance-trained athletes (-0.90 ± 1.27 mm, i.e. -12 ± 16% of the total response). Meanwhile, oxygenated haemoglobin increased throughout the second part of exercise and was significantly higher at the end of exercise compared with the value at 120 s (P < 0.05), whereas the integrated EMG was not significantly changed throughout exercise. In sedentary subjects, a slow component was simultaneously observed for V(O(2P)) and [PCr] time-dependent changes (208 ± 14 ml min(-1), i.e. 38 ± 18% of the total V(O(2P))response, and 1.82 ± 1.39 mm, i.e. 16 ± 13% of the total [PCr] response), but the corresponding absolute or relative amplitudes were not correlated. The integrated EMG was significantly increased throughout exercise in sedentary subjects. Taken together, our results challenge the hypothesis of a mechanistic link between [PCr] and V(O(2P)) slow components and demonstrate that, as a result of a tighter metabolic control and increased O(2) availability, the [PCr] slow component can be minimized in endurance-trained athletes while the V(O(2P)) slow component occurs.
    Mots-clés : Adult, crmbm, Electromyography, Exercise, Female, Humans, Knee, Magnetic Resonance Spectroscopy, Male, Muscle Contraction, Muscle, Skeletal, Oxygen Consumption, Phosphocreatine, Physical Endurance, Pulmonary Gas Exchange, Sedentary Lifestyle, Young Adult.


Journal Article

  • Gondin, J, Giannesini, B, Vilmen, C, Le Fur, Y, Cozzone, PJ & Bendahan, D 2011, “Effects of a single bout of isometric neuromuscular electrical stimulation on rat gastrocnemius muscle: a combined functional, biochemical and MRI investigation”, Journal of electromyography and kinesiology: official journal of the International Society of Electrophysiological Kinesiology, vol. 21, no. 3, p. 525-532.
    Résumé : While muscle damage resulting from electrically-induced muscle isometric contractions has been reported in humans, animal studies have failed to illustrate similar deleterious effects and it remains to be determined whether these conflicting results are related to differences regarding experimental procedures or to species. We have investigated in vivo, in rat gastrocnemius muscles, using experimental conditions as close as possible to those used in humans (i.e., muscle length, number of contractions, stimulated muscle), the effects of a single bout of neuromuscular electrical stimulation (NMES). Maximal tetanic force was measured before, immediately after and 1h and 1, 2, 3, 7 and 14 days after NMES. Magnetic resonance imaging measurements, including volume of gastrocnemius muscles and proton transverse relaxation time (T(2)) were performed at baseline and 3, 7, and 14 days after the NMES session. Control animals did not perform any exercise and measurements were recorded at the same time points. For both groups, blood creatine kinase (CK) activity was measured within the first 3 days that followed the initial evaluation. Maximal tetanic force decreased immediately after NMES whereas measurements performed 1h and the days afterwards were similar to the baseline values. CK activity, muscle volume and T(2) values were similar throughout the experimental protocol between the two groups. Under carefully controlled experimental conditions, isometric NMES per se did not induce muscle damage in rat gastrocnemius muscles on the contrary to what has been repeatedly reported in humans. Further experiments would then be warranted in order to clearly delineate these differences and to better understand the physiological events associated with muscle damage resulting from NMES-induced isometric contractions.
    Mots-clés : Animals, crmbm, Electric Stimulation, Isometric Contraction, Magnetic Resonance Imaging, Male, Muscle Fatigue, Muscle, Skeletal, Physical Endurance, Rats, Rats, Wistar.

  • Layec, G, Bringard, A, Le Fur, Y, Vilmen, C, Micallef, J-P, Perrey, S, Cozzone, PJ & Bendahan, D 2011, “Comparative determination of energy production rates and mitochondrial function using different 31P MRS quantitative methods in sedentary and trained subjects”, NMR in biomedicine, vol. 24, no. 4, p. 425-438.
    Résumé : Muscle energetics has been largely and quantitatively investigated using (31)P MRS. Various methods have been used to estimate the corresponding rate of oxidative ATP synthesis (ATP(ox)); however, potential differences among methods have not been investigated. In this study, we aimed to compare the rates of ATP production and energy cost in two groups of subjects with different training status using four different methods: indirect method (method 1), ADP control model (method 2) and phosphate potential control model (method 3). Method 4 was a modified version of method 3 with the introduction of a correction factor allowing for similar values to be obtained for the end-exercise oxidative ATP synthesis rate inferred from exercise measurements and the initial recovery phosphocreatine resynthesis rate. Seven sedentary and seven endurance-trained subjects performed a dynamic standardised rest-exercise-recovery protocol. We quantified the rates of ATP(ox) and anaerobic ATP synthesis (ATP(ana)) using (31)P MRS data recorded at 1.5 T. The rates of ATP(ox) over the entire exercise session were independent of the method used, except for method 4 which provided significantly higher values in both groups (p < 0.01). In addition, methods 1-3 were cross-correlated, thereby confirming their statistical agreement. The rate of ATP(ana) was significantly higher with method 1 (p < 0.01) and lower with method 4 (p < 0.01). As a result of the higher rate of ATP(ox), EC (method 4) calculated over the entire exercise session was higher and initial EC (method 1) was lower in both groups compared with the other methods. We showed in this study that the rate of ATP(ox) was independent of the calculation method, as long as no corrections (method 4) were performed. In contrast, results related to the rates of ATP(ana) were strongly affected by the calculation method and, more exactly, by the estimation of protons generated by ATP(ox). Although the absolute EC values differed between the methods, within- or between-subject comparisons are still valid given the tight relationships between them.
    Mots-clés : Adenosine Diphosphate, Adenosine Triphosphate, Adult, Anaerobiosis, crmbm, Energy Metabolism, Exercise, Female, Humans, Hydrogen-Ion Concentration, Knee, Magnetic Resonance Spectroscopy, Male, Mitochondria, Muscle, Muscles, Oxidation-Reduction, Phosphorus Isotopes, Phosphorylation, Sedentary Lifestyle.


Journal Article

  • Giannesini, B, Vilmen, C, Le Fur, Y, Dalmasso, C, Cozzone, PJ & Bendahan, D 2010, “A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle”, Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 64, no. 1, p. 262-270.
    Résumé : MR techniques have proven their ability to investigate skeletal muscle function in situ. Their benefit in terms of noninvasiveness is, however, lost in animal research, given that muscle stimulation and force output measurements are usually achieved using invasive surgical procedures, thereby excluding repeated investigations in the same animal. This study describes a new setup allowing strictly noninvasive investigations of mouse gastrocnemius muscle function using (1)H-MRI and (31)P-MR spectroscopy. Its originality is to integrate noninvasive systems for inducing muscle contraction through transcutaneous stimulation and for measuring mechanical performance with a dedicated ergometer. In order to test the setup, muscle function was investigated using a fatiguing stimulation protocol (6 min of repeated isometric contractions at 1.7 Hz). T(2)-weighted imaging demonstrated that transcutaneous stimulation mainly activated the gastrocnemius. Moreover, investigations repeated twice with a 7-day interval between bouts did show a high reproducibility in measurements with regard to changes in isometric force and energy metabolism. In conclusion, this setup enables us for the first time to access mechanical performance, energy metabolism, anatomy, and physiology strictly noninvasively in contracting mouse skeletal muscle. The possibility for implementing longitudinal studies opens up new perspectives in many research areas, including ageing, pharmaceutical research, and gene and cell therapy.
    Mots-clés : Animals, Energy Metabolism, Hindlimb, Longitudinal Studies, Magnetic Resonance Spectroscopy, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Reproducibility of Results.

  • Gondin, J, Giannesini, B, Vilmen, C, Dalmasso, C, le Fur, Y, Cozzone, PJ & Bendahan, D 2010, “Effects of stimulation frequency and pulse duration on fatigue and metabolic cost during a single bout of neuromuscular electrical stimulation”, Muscle & nerve, vol. 41, no. 5, p. 667-678.
    Résumé : We have investigated the effects of stimulation frequency and pulse duration on fatigue and energy metabolism in rat gastrocnemius muscle during a single bout of neuromuscular electrical stimulation (NMES). Electrical pulses were delivered at 100 Hz (1-ms pulse duration) and 20 Hz (5-ms pulse duration) for the high (HF) and low (LF) frequency protocols, respectively. As a standardization procedure, the averaged stimulation intensity, the averaged total charge, the initial peak torque, the duty cycle, the contraction duration and the torque-time integral were similar in both protocols. Fatigue was assessed using two testing trains delivered at a frequency of 100 Hz and 20 Hz before and after each protocol. Metabolic changes were investigated in vivo using 31P-magnetic resonance spectroscopy (31P-MRS) and in vitro in freeze-clamped muscles. Both LF and HF NMES protocols induced the same decrease in testing trains and metabolic changes. We conclude that, under carefully controlled and comparable conditions, the use of low stimulation frequency and long pulse duration do not minimize the occurrence of muscle fatigue or affect the corresponding stimulation-induced metabolic changes so that this combination of stimulation parameters would not be adequate in the context of rehabilitation.
    Mots-clés : Adenosine Triphosphate, Animals, crmbm, Electric Stimulation, Electric Stimulation Therapy, Energy Metabolism, Exercise Tolerance, Magnetic Resonance Spectroscopy, Male, Motor Neurons, Muscle Contraction, Muscle Fatigue, Muscle Fibers, Skeletal, Muscle Weakness, Muscle, Skeletal, Neuromuscular Junction, Peripheral Nerves, Rats, Rats, Wistar, Time Factors.

  • Tonson, A, Ratel, S, Le Fur, Y, Vilmen, C, Cozzone, PJ & Bendahan, D 2010, “Muscle energetics changes throughout maturation: a quantitative 31P-MRS analysis”, Journal of applied physiology (Bethesda, Md.: 1985), vol. 109, no. 6, p. 1769-1778.
    Résumé : We quantified energy production in 7 prepubescent boys (11.7 ± 0.6 yr) and 10 men (35.6 ± 7.8 yr) using (31)P-magnetic resonance spectroscopy to investigate whether development affects muscle energetics, given that resistance to fatigue has been reported to be larger before puberty. Each subject performed a finger flexions exercise at 0.7 Hz against a weight adjusted to 15% of their maximal voluntary strength for 3 min, followed by a 15-min recovery period. The total energy cost was similar in both groups throughout the exercise bout, whereas the interplay of the different metabolic pathways was different. At the onset of exercise, children exhibited a higher oxidative contribution (50 ± 15% in boys and 25 ± 8% in men, P < 0.05) to ATP production, whereas the phosphocreatine breakdown contribution was reduced (40 ± 10% in boys and 53 ± 12% in men, P < 0.05), likely as a compensatory mechanism. The anaerobic glycolysis activity was unaffected by maturation. The recovery phase also disclosed differences regarding the rates of proton efflux (6.2 ± 2.5 vs. 3.8 ± 1.9 mM · pH unit(-1) · min(-1), in boys and men, respectively, P < 0.05), and phosphocreatine recovery, which was significantly faster in boys than in men (rate constant of phosphocreatine recovery: 1.3 ± 0.5 vs. 0.7 ± 0.4 min(-1); V(max): 37.5 ± 14.5 vs. 21.1 ± 12.2 mM/min, in boys and men, respectively, P < 0.05). Our results obtained in vivo clearly showed that maturation affects muscle energetics. Children relied more on oxidative metabolism and less on creatine kinase reaction to meet energy demand during exercise. This phenomenon can be explained by a greater oxidative capacity, probably linked to a higher relative content in slow-twitch fibers before puberty.
    Mots-clés : Adenosine Triphosphate, Adolescent, Adult, Child, Creatine Kinase, Energy Metabolism, Glycolysis, Hand Strength, Humans, Isometric Contraction, Kinetics, Magnetic Resonance Spectroscopy, Male, Middle Aged, Muscle Development, Muscle, Skeletal, Oxidation-Reduction, Phosphocreatine, Phosphorus Isotopes, Recovery of Function, Sexual Development, Young Adult.


Journal Article

  • Layec, G, Bringard, A, Le Fur, Y, Vilmen, C, Micallef, J-P, Perrey, S, Cozzone, PJ & Bendahan, D 2009, “Reproducibility assessment of metabolic variables characterizing muscle energetics in vivo: A 31P-MRS study”, Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, vol. 62, no. 4, p. 840-854.
    Résumé : The purpose of the present study was to assess the reliability of metabolic parameters measured using (31)P magnetic resonance spectroscopy ((31)P MRS) during two standardized rest-exercise-recovery protocols. Twelve healthy subjects performed the standardized protocols at two different intensities; i.e., a moderate intensity (MOD) repeated over a two-month period and heavy intensity (HEAVY) repeated over a year's time. Test-retest reliability was analyzed using coefficient of variation (CV), limits of agreement (LOA), and intraclass correlation coefficients (ICC). During exercise and recovery periods, most of the metabolic parameters exhibited a good reliability. The CVs of individual concentration of phosphocreatine ([PCr]), concentration of adenosine diphosphate ([ADP]), and pH values recorded at end of the HEAVY exercise were lower than 15%. The CV calculated for the rate of PCr resynthesis and the maximal oxidative capacity were less than 13% during the HEAVY protocol. Inferred parameters such as oxidative and total adenosine triphosphate (ATP) production rates exhibited a good reliability (ICC approximately 0.7; CV < 15% during the HEAVY protocol). Our results demonstrated that measurement error using (31)P-MRS during a standardized exercise was low and that biological variability accounted for the vast majority of the measurement variability. In addition, the corresponding metabolic measurements can reliably be used for longitudinal studies performed even over a long period of time.
    Mots-clés : Adult, crmbm, Energy Metabolism, Female, Humans, Magnetic Resonance Spectroscopy, Male, Muscle, Skeletal, Phosphocreatine, Phosphorus Isotopes, Physical Exertion, Reproducibility of Results, Sensitivity and Specificity.

  • Layec, G, Bringard, A, Le Fur, Y, Vilmen, C, Micallef, J-P, Perrey, S, Cozzone, PJ & Bendahan, D 2009, “Effects of a prior high-intensity knee-extension exercise on muscle recruitment and energy cost: a combined local and global investigation in humans”, Experimental physiology, vol. 94, no. 6, p. 704-719.
    Résumé : The effects of a priming exercise bout on both muscle energy production and the pattern of muscle fibre recruitment during a subsequent exercise bout are poorly understood. The purpose of the present study was to determine whether a prior exercise bout which is known to increase O(2) supply and to induce a residual acidosis could alter energy cost and muscle fibre recruitment during a subsequent heavy-intensity knee-extension exercise. Fifteen healthy subjects performed two 6 min bouts of heavy exercise separated by a 6 min resting period. Rates of oxidative and anaerobic ATP production, determined with (31)P-magnetic resonance spectroscopy, and breath-by-breath measurements of pulmonary oxygen uptake were obtained simultaneously. Changes in muscle oxygenation and muscle fibre recruitment occurring within the quadriceps were measured using near-infrared spectroscopy and surface electromyography. The priming heavy-intensity exercise increased motor unit recruitment (P < 0.05) in the early part of the subsequent exercise bout but did not alter muscle energy cost. We also observed a reduced deoxygenation time delay, whereas the deoxygenation amplitude was increased (P < 0.01). These changes were associated with an increased oxidative ATP cost after approximately 50 s (P < 0.05) and a slight reduction in the overall anaerobic rate of ATP production (0.11 +/- 0.04 mM min(-1) W(-1) for bout 1 and 0.06 +/- 0.11 mM min(-1) W(-1) for bout 2; P < 0.05). We showed that a priming bout of heavy exercise led to an increased recruitment of motor units in the early part of the second bout of heavy exercise. Considering the increased oxidative cost and the unaltered energy cost, one could suggest that our results illustrate a reduced metabolic strain per fibre.
    Mots-clés : Adenosine Triphosphate, Adult, Aerobiosis, Anaerobiosis, crmbm, Electromyography, Energy Metabolism, Exercise, Exercise Test, Female, Humans, Knee, Magnetic Resonance Spectroscopy, Male, Models, Biological, Muscle Fibers, Skeletal, Muscle, Skeletal, Oxygen Consumption, Recruitment, Neurophysiological, Spectroscopy, Near-Infrared.

  • Layec, G, Bringard, A, Vilmen, C, Micallef, J-P, Le Fur, Y, Perrey, S, Cozzone, PJ & Bendahan, D 2009, “Does oxidative capacity affect energy cost? An in vivo MR investigation of skeletal muscle energetics”, European journal of applied physiology, vol. 106, no. 2, p. 229-242.
    Résumé : Investigations of training effects on exercise energy cost have yielded conflicting results. The purpose of the present study was to compare quadriceps energy cost and oxidative capacity between endurance-trained and sedentary subjects during a heavy dynamic knee extension exercise. We quantified the rates of ATP turnover from oxidative and anaerobic pathways with (31)P-MRS, and we measured simultaneously pulmonary oxygen uptake in order to assess both total ATP production [i.e., energy cost (EC)] and O(2) consumption (O(2) cost) scaled to power output. Seven sedentary (SED) and seven endurance-trained (TRA) subjects performed a dynamic standardized rest-exercise-recovery protocol at an exercise intensity corresponding to 35% of maximal voluntary contraction. We showed that during a dynamic heavy exercise, the O(2) cost and EC were similar in the SED and endurance-trained groups. For a given EC, endurance-trained subjects exhibited a higher relative mitochondrial contribution to ATP production at the muscle level (84 +/- 12% in TRA and 57 +/- 12% in SED; P < 0.01) whereas the anaerobic contribution was reduced (18 +/- 12% in TRA and 44 +/- 11% in SED; P < 0.01). Our results obtained in vivo illustrate that on the one hand the beneficial effects of endurance training are not related to any reduction in EC or O(2) cost and on the other hand that this similar EC was linked to a change regarding the contribution of anaerobic and oxidative processes to energy production, i.e., a greater aerobic energy contribution associated with a concomitant reduction of the anaerobic energy supply.
    Mots-clés : Adenosine Triphosphate, Adult, Anaerobiosis, crmbm, Humans, Magnetic Resonance Spectroscopy, Male, Muscle, Skeletal, Oxidation-Reduction, Oxygen Consumption, Physical Endurance.


Journal Article

  • Layec, G, Bringard, A, Vilmen, C, Micallef, J-P, Fur, YL, Perrey, S, Cozzone, PJ & Bendahan, D 2008, “Accurate work-rate measurements during in vivo MRS studies of exercising human quadriceps”, Magma (New York, N.Y.), vol. 21, no. 3, p. 227-235.
    Résumé : INTRODUCTION: Given that we have reached a point in the field of muscle energetics where absolute measurements are warranted to take the area forward, we designed an ergometer, including two force and two displacement transducers, allowing dynamic and isometric knee extension within a MR system and accurate measurements of power output. METHODS: On the basis of repeated measurements, the force and displacement transducers accuracy was 1% for values ranging from 0 to 394 N and 4% for values ranging from 0 to 20 cm. In addition, measurements were not affected by magnetic field. MRS experiments in exercising muscle were conducted in eight subjects. They performed two standardized dynamic alternate leg extension exercises (25 and 35% of MVC) while the corresponding metabolic changes were measured using (31)P-MRS. RESULTS: The mean power output produced during both exercises were 63 +/- 16 and 81 +/- 15 W while the eccentric work was reduced i.e. 12 +/- 14 and 21 +/- 6 W for the moderate and heavy exercise respectively. The corresponding metabolic changes were significant with a 20-40% PCr depletion and an end of exercise pH ranging from 0.02 to 0.70 pH units. CONCLUSION: Overall, the present ergometer allows quadriceps exercise in a MR system and should be useful for future metabolic studies for which reliable and absolute quantification of power output is warranted.
    Mots-clés : crmbm, Ergometry, Exercise, Humans, Magnetic Resonance Spectroscopy, Quadriceps Muscle.
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