Gwenael Layec

Peripheral fatigue limits endurance exercise via a sensory feedback-mediated reduction in spinal motoneuronal output

This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 (P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P < 0.01). Additionally, ΔQtw,pot following Leg2-post was less than Leg2 (33 ± 3 vs 52 ± 3%; P < 0.01). Although the slope of iEMG was similar during Leg2 and Leg2-post, end-exercise iEMG following Leg2-post was 26% lower compared with Leg2 (P < 0.05). Despite a similar rate of rise, RPE was consistently ∼28% higher throughout Leg2-post vs. Leg2 (P < 0.05). In conclusion, this study provides evidence that peripheral fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.

Reproducibility assessment of metabolic variables characterizing muscle energetics in Vivo: A 31P-MRS study

The purpose of the present study was to assess the reliability of metabolic parameters measured using 31P magnetic resonance spectroscopy (31P 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 years 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 ≈ 0.7; CV < 15% during the HEAVY protocol). Our results demonstrated that measurement error using 31P‐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. Magn Reson Med, 2009.

Nitric oxide and passive limb movement: a new approach to assess vascular function

•  Passive limb movement elicits a robust increase in limb blood flow (LBF) and limb vascular conductance (LVC) without a concomitant increase in skeletal muscle metabolism. •  The peripheral vascular mechanisms associated with the increase in LBF and LVC are unknown. •  Using an intra‐arterial infusion of NG‐monomethyl‐l‐arginine (l‐NMMA) to inhibit nitric oxide synthase (NOS) the hyperaemic and vasodilatory response to passive limb movement was attenuated by nearly 80%. •  This finding demonstrates that the increases in LBF and LVC during passive limb movement are primarily NO dependent. •  Passive limb movement appears to have significant promise as a new approach to assess NO‐mediated vascular function, an important predictor of cardiovascular disease risk.

Effects of a prior high‐intensity knee‐extension exercise on muscle recruitment and energy cost: a combined local and global investigation in humans

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 O2 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 31P‐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 ∼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.

In vivo evidence of an age-related increase in ATP cost of contraction in the plantar flexor muscles

Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered haemodynamic response to exercise in the elderly. Thus we examined whether (i) the ATP cost of contraction increases with age, and (ii) this results in altered convective O(2) delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining (31)P-MRS (magnetic resonance spectroscopy), Doppler ultrasound imaging and NIRS (near-IR spectroscopy) during dynamic plantar flexion exercise at 40% of WR(max) (maximal power output) in 20 healthy young and 20 older subjects matched for physical activity. The ATP cost of contraction was significantly higher in the old (7.2±4.1 mM/min per W) compared with the young (2.4±1.9 mM/min per W; P<0.05) and this was only significantly correlated with the plantar flexion WR(max) value in the old subjects (r=-0.52; P<0.05). Even when differences in power output were taken into account, end-exercise blood flow (old, 259±168 ml/min per W and young, 134±40 ml/min per W; P<0.05) and convective O(2) delivery (old, 0.048±0.031 l/min per W and young, 0.026±0.008 l/min per W; P<0.05) were greater in the old in comparison with the young subjects. In contrast, the NIRS oxyhaemoglobin, deoxyhaemoglobin and microvascular oxygenation indices were not significantly different between the groups (P>0.05). Therefore the present study reveals that, although the peripheral haemodynamic responses to plantar flexion exercise appear to be appropriate, the elevated energy cost of contraction and associated reduction in the WR(max) value in this muscle group may play a role in limiting exercise capacity with age.

Comparative determination of energy production rates and mitochondrial function using different 31P MRS quantitative methods in sedentary and trained subjects.

Muscle energetics has been largely and quantitatively investigated using 31P MRS. Various methods have been used to estimate the corresponding rate of oxidative ATP synthesis (ATPox); 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 ATPox and anaerobic ATP synthesis (ATPana) using 31P MRS data recorded at 1.5 T. The rates of ATPox 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 ATPana 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 ATPox, 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 ATPox was independent of the calculation method, as long as no corrections (method 4) were performed. In contrast, results related to the rates of ATPana were strongly affected by the calculation method and, more exactly, by the estimation of protons generated by ATPox. Although the absolute EC values differed between the methods, within‐ or between‐subject comparisons are still valid given the tight relationships between them. Copyright

Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: preliminary findings

Impaired metabolism in peripheral skeletal muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine the energy cost and skeletal muscle energetics in six patients with COPD during dynamic plantar flexion exercise compared with six well-matched healthy control subjects. Patients with COPD displayed a higher energy cost of muscle contraction compared with the controls (control: 6.1 ± 3.1% of rest·min(-1)·W(-1), COPD: 13.6 ± 8.3% of rest·min(-1)·W(-1), P = 0.01). Although, the initial phosphocreatine resynthesis rate was also significantly attenuated in patients with COPD compared with controls (control: 74 ± 17% of rest/min, COPD: 52 ± 13% of rest/min, P = 0.04), when scaled to power output, oxidative ATP synthesis was similar between groups (6.5 ± 2.3% of rest·min(-1)·W(-1) in control and 7.8 ± 3.9% of rest·min(-1)·W(-1) in COPD, P = 0.52). Therefore, our results reveal, for the first time that in a small subset of patients with COPD a higher ATP cost of muscle contraction may substantially contribute to the lower mechanical efficiency previously reported in this population. In addition, it appears that some patients with COPD have preserved mitochondrial function and normal energy supply in lower limb skeletal muscle.

Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans.

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used 31P‐magnetic resonance spectroscopy (31P‐MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min‐1, CVinter‐subject = 42%) as compared with PF (46 ± 20 mM min‐1, CVinter‐subject = 44%) and tended to be higher in FF (43 ± 35 mM min‐1, CVinter‐subject = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end‐exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end‐exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter‐ and intra‐individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright

Passive leg movement and nitric oxide-mediated vascular function: the impact of age

UNLABELLED In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; L-NMMA 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; L-NMMA 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

Symmorphosis and skeletal muscle V̇O2 max : in vivo and in vitro measures reveal differing constraints in the exercise-trained and untrained human.

The concept of symmorphosis predicts that the capacity of each step of the oxygen cascade is attuned to the task demanded of it during aerobic exercise at maximal rates of oxygen consumption ( V̇O2 max ) such that no single process is limiting or in excess at V̇O2 max . The present study challenges the applicability of this concept to humans by revealing clear, albeit very different, limitations and excesses in oxygen supply and consumption among untrained and endurance‐trained humans. Among untrained individuals, V̇O2 max is limited by the capacity of the mitochondria to consume oxygen, despite an excess of oxygen supply, whereas, among trained individuals, V̇O2 max is limited by the supply of oxygen to the mitochondria, despite an excess of mitochondrial respiratory capacity.