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Introduction: This study investigated the magnitude and etiology of neuromuscular fatigue and muscle damage induced by eccentric cycling compared with conventional concentric cycling in patients with breast cancer., Methods: After a gradual familiarization protocol for eccentric cycling, nine patients with early-stage breast cancer performed three cycling sessions in eccentric or concentric mode. The eccentric cycling session (ECC) was compared with concentric cycling sessions matched for power output (CON power ; 80% of concentric peak power output, 95 ± 23 W) or oxygen uptake ( ; 10 ± 2 mL·min·kg -1 ). Preexercise to postexercise changes (30-s through 10-min recovery) in knee extensor maximal voluntary contraction force (MVC), voluntary activation, and quadriceps potentiated twitch force ( Qtw ) were quantified to determine global, central, and peripheral fatigue, respectively. Creatine kinase and lactate dehydrogenase activities were measured in the plasma before and 24 h after exercise as markers of muscle damage., Results: Compared with CON power (-11% ± 9%) and (-5% ± 5%), the ECC session resulted in a greater decrease in MVC (-25% ± 12%) postexercise ( P < 0.001). Voluntary activation decreased only in ECC (-9% ± 6% postexercise, P < 0.001). The decrease in Qtw was similar postexercise between ECC and CON power (-39% ± 21% and -40% ± 16%, P > 0.99) but lower in ( P < 0.001). The CON power session resulted in twofold greater compared with the ECC and sessions ( P < 0.001). No change in creatine kinase or lactate dehydrogenase activity was reported from preexercise to 24 h postexercise., Conclusions: The ECC session induced greater neuromuscular fatigue compared with the concentric cycling sessions without generating severe muscle damage. ECC is a promising exercise modality for counteracting neuromuscular maladaptation in patients with breast cancer., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: Breast cancer patients are commonly treated with sequential administrations of epirubicin-cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients., Methods: Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed vastus lateralis skeletal muscle biopsies either before the first administration (pre) of EC (50 ± 14 years) or TAX (50 ± 16 years) and 4 days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed., Results: Decrease in muscle fibres cross-sectional area was only observed post-EC (-25%; P < 0.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)-linked substrate state (-32%; P = 0.001), oxidative phosphorylation (OXPHOS) by CI (-35%; P = 0.002), CI&CII (-26%; P = 0.022) and CII (-24%; P = 0.027). If H 2 O 2 production was unchanged post-EC, an increase was observed post-TAX for OXPHOS by CII (+25%; P = 0.022). We found a decrease in makers of mitochondrial content, as shown post-EC by a decrease in the protein levels of citrate synthase (-53%; P < 0.001) and VDAC (-39%; P < 0.001). Despite no changes in markers of mitochondrial fission, a decrease in the expression of a marker of mitochondrial inner-membrane fusion was found post-EC (OPA1; -60%; P < 0.001). We explored markers of mitophagy and found reductions post-EC in the protein levels of PINK1 (-63%; P < 0.001) and Parkin (-56%; P = 0.005), without changes post-TAX. An increasing trend in Bax protein level was found post-EC (+96%; P = 0.068) and post-TAX (+77%; P = 0.073), while the Bcl-2 level was decreased only post-EC (-52%; P = 0.007). If an increasing trend in TUNEL-positive signal was observed post-EC (+68%; P = 0.082), upregulation was highlighted post-TAX (+86%; P < 0.001), suggesting activation of the apoptosis process., Conclusions: We demonstrated that a single administration of EC induced, in only 4 days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H 2 O 2 production., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: Critical torque (CT) and work done above it ( W ') are key predictors of exercise performance associated with neuromuscular fatigue. The aim of the present study was to understand the role of the metabolic cost of exercise in determining exercise tolerance, CT and W ', and the mechanisms of neuromuscular fatigue., Methods: Twelve subjects performed four knee extension time trials (6, 8, 10, and 12 min) using eccentric, isometric, or concentric contractions (3-s on/2-s off at 90°·s -1 or 30°·s -1 ) to modulate the metabolic cost of exercise. Exercise performance was quantified by total impulse and mean torque. Critical torque and W ' were determined using the linear relationship between total impulse and contraction time. Cardiometabolic, neuromuscular, and ventilatory responses were quantified. Neuromuscular function was evaluated by maximal voluntary contraction, resting potentiated single/doublet electrical stimulations, and superimposed single electrical stimulation to quantify neuromuscular, peripheral, and central fatigue, respectively., Results: Compared with isometric exercise, total impulse (+36% ± 21%; P < 0.001), CT (+27% ± 30%; P < 0.001), and W ' (+67% ± 99%; P < 0.001) were increased during eccentric exercise, whereas total impulse (-25% ± 7%; P < 0.001), critical torque (-26% ± 15%; P < 0.001), and W ' (-18% ± 19%; P < 0.001) were reduced in concentric exercise. Conversely, the metabolic response and the degree of peripheral fatigue were reduced during eccentric exercise, whereas they were increased during concentric exercise. Critical torque was negatively associated with oxygen consumption gain ( R2 = 0.636; P < 0.001), and W ' was negatively associated with rates of neuromuscular and peripheral fatigue indices ( R2 = 0.252-0.880; P < 0.001)., Conclusions: The contraction mode influenced both CT and W ', and consequently exercise tolerance, indicating that the metabolic cost of contraction played a key role., (Copyright © 2023 by the American College of Sports Medicine.)

Purpose: The present study aimed to characterize the etiology of exercise-induced neuromuscular fatigue and its consequences on the force-duration relationship to provide mechanistic insights into the reduced exercise capacity characterizing early-stage breast cancer patients., Methods: Fifteen early-stage breast cancer patients and fifteen healthy women performed 60 maximal voluntary isometric quadriceps contractions (MVCs, 3 s of contraction, 2 s of relaxation). The critical force was determined as the mean force of the last six contractions, while W' was calculated as the force impulse generated above the critical force. Quadriceps muscle activation during exercise was estimated from vastus lateralis, vastus medialis and rectus femoris EMG. Central and peripheral fatigue were quantified via changes in pre- to postexercise quadriceps voluntary activation (ΔVA) and quadriceps twitch force (ΔQTw) evoked by supramaximal electrical stimulation, respectively., Results: Early-stage breast cancer patients demonstrated lower MVC than controls preexercise (- 15%, P = 0.022), and this reduction persisted throughout the 60-MVC exercise (- 21%, P = 0.002). The absolute critical force was lower in patients than in controls (144 ± 29N vs. 201 ± 47N, respectively, P < 0.001), while W' was similar (P = 0.546), resulting in lower total work done (- 23%, P = 0.001). This was associated with lower muscle activation in the vastus lateralis (P < 0.001), vastus medialis (P = 0.003) and rectus femoris (P = 0.003) in patients. Immediately following exercise, ΔVA showed a greater reduction in patients compared to controls (- 21.6 ± 13.3% vs. - 12.6 ± 7.7%, P = 0.040), while ΔQTw was similar (- 60.2 ± 13.2% vs. - 52.8 ± 19.4%, P = 0.196)., Conclusion: These findings support central fatigue as a primary cause of the reduction in exercise capacity characterizing early-stage breast cancer patients treated with chemotherapy., Clinical Trials Registration: No. NCT04639609-November 20, 2020., (© 2023. The Author(s).)

Background: Fatigue is a hallmark of breast cancer and is associated with skeletal muscle deconditioning. If cancer-related fatigue occurs early during chemotherapy (CT), the development of skeletal muscle deconditioning and its effect on exercise capacity remain unclear. The aim of this study was to investigate the evolution of skeletal muscle deconditioning and exercise capacity in patients with early-stage breast cancer during CT., Methods: Patients with breast cancer had a visit before undergoing CT, at 8 weeks, and at the end of chemotherapy (post-CT). Body composition was determined through bioelectrical impedance analysis. Knee extensor, handgrip muscle force and fatigue was quantified by performing maximal voluntary isometric contractions and exercise capacity using the 6-min walking test. Questionnaires were also administered to evaluate quality of life, cancer-related fatigue, and physical activity level., Results: Among the 100 patients, reductions were found in muscle mass (-2.3%, p = .002), exercise capacity (-6.7%, p < .001), and knee extensor force (-4.9%, p < .001) post-CT, which occurred within the first 8 weeks of treatment with no further decrease thereafter. If muscle fatigue did not change, handgrip muscle force decreased post-CT only (-2.5%, p = .001), and exercise capacity continued to decrease between 8 weeks and post-CT (-4.6%, p < .001). Quality of life and cancer-related fatigue were impaired after 8 weeks (p < .001) and remained stable thereafter, whereas the physical activity level remained stable during chemotherapy., Conclusions: Similar to cancer-related fatigue, skeletal muscle deconditioning and reduced exercise capacity occurred early during breast cancer CT. Thus, it appears essential to prevent these alterations through exercise training implemented during CT., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: The present study investigated the mechanisms of neuromuscular fatigue in quadriceps and hamstring muscles and its consequences on the torque-duration relationship., Methods: Twelve healthy men performed a 5-min all-out exercise (3-s contraction, 2-s relaxation) with either quadriceps or hamstring muscles on separate days. Central fatigue and peripheral fatigue were quantified via changes in pre- to postexercise voluntary activation (VA) and potentiated twitch (P Tw ) torque evoked by supramaximal electrical stimulation, respectively. Critical torque was determined as the mean torque of the last six contractions, whereas W ' was calculated as the torque impulse done above critical torque., Results: After exercise, maximal voluntary contraction (MVC) decreased to a greater magnitude ( P < 0.001) in quadriceps (-67% ± 9%) compared with hamstring (-51% ± 10%). ∆P Tw was also greater in quadriceps compared with hamstring (-69% ± 15% vs 55% ± 10%, P < 0.01), whereas central fatigue only developed in quadriceps (∆VA, -25% ± 28%). Hamstring demonstrated reduced critical torque compared with quadriceps (60 ± 12 vs 97 ± 26 N·m, P < 0.001) as well as drastically lower W ' (1001 ± 696 vs 8111 ± 2073 N·m·s, P < 0.001). No correlation was found between quadriceps and hamstring for any index of neuromuscular fatigue (∆MVC, ∆P Tw , or ∆VA)., Conclusions: These findings revealed that hamstring presented different etiology and magnitude of neuromuscular fatigue compared with quadriceps. The absence of correlation observed between quadriceps and hamstring fatigue parameters (∆MVC, ∆P Tw , or ∆VA) suggests no interrelation in fatigue etiology between these two muscle groups within individuals and, therefore, highlights the need to investigate specifically hamstring muscle fatigue., (Copyright © 2022 by the American College of Sports Medicine.)

Purpose: This study evaluated whether central motor drive during fatiguing exercise plays a role in determining performance and the development of neuromuscular fatigue during a subsequent endurance task., Methods: On separate days, 10 males completed three constant-load (80% peak power output), single-leg knee-extension trials to task failure in a randomized fashion. One trial was performed without preexisting quadriceps fatigue (CON), and two trials were performed with preexisting quadriceps fatigue induced either by voluntary (VOL; involving central motor drive) or electrically evoked (EVO; without central motor drive) quadriceps contractions (~20% maximal voluntary contraction (MVC)). Neuromuscular fatigue was assessed via pre-post changes in MVC, voluntary activation (VA), and quadriceps potentiated twitch force ( Qtw,pot ). Cardiorespiratory responses and rating of perceived exertion were also collected throughout the sessions. The two prefatiguing protocols were matched for peripheral fatigue and stopped when Qtw,pot declined by ~35%., Results: Time to exhaustion was shorter in EVO (4.3 ± 1.3 min) and VOL (4.7 ± 1.5 min) compared with CON (10.8 ± 3.6 min, P < 0.01) with no difference between EVO and VOL. ΔMVC (EVO: -47% ± 8%, VOL: -45% ± 8%, CON: -53% ± 8%), Δ Qtw,pot (EVO: -65% ± 7%, VOL: -59% ± 14%, CON: -64% ± 9%), and ΔVA (EVO: -9% ± 7%, VOL: -8% ± 5%, CON: -7% ± 5%) at the end of the dynamic task were not different between conditions (all P > 0.05). Compared with EVO (10.6 ± 1.7) and CON (6.8 ± 0.8), rating of perceived exertion was higher ( P = 0.05) at the beginning of VOL (12.2 ± 1.0)., Conclusions: These results suggest that central motor drive involvement during prior exercise plays a negligible role on the subsequent endurance performance. Therefore, our findings indicate that peripheral fatigue-mediated impairments are the primary determinants of high-intensity single-leg endurance performance., (Copyright © 2022 by the American College of Sports Medicine.)

Chemotherapy is a common therapy to treat patients with breast cancer but also leads to skeletal muscle deconditioning. Skeletal muscle deconditioning is multifactorial and intermuscular adipose tissue (IMAT) accumulation is closely linked to muscle dysfunction. To date, there is no clinical study available investigating IMAT development through a longitudinal protocol and the underlying mechanisms remain unknown. Our study was dedicated to investigating IMAT content in patients with early breast cancer who were treated with chemotherapy and exploring the subsequent cellular mechanisms involved in its development. We included 13 women undergoing chemotherapy. Muscle biopsies and ultrasonography assessment were performed before and after chemotherapy completion. Histological and Western blotting analyses were conducted. We found a substantial increase in protein levels of three mature adipocyte markers (perilipin, +901%; adiponectin, +135%; FABP4, +321%; P < 0.05). These results were supported by an increase in oil red O-positive staining (+358%; P < 0.05). A substantial increase in PDGFRα protein levels was observed (+476%; P < 0.05) highlighting an increase in fibro-adipogenic progenitors (FAPs) content. The cross-sectional area of the vastus lateralis muscle fibers substantially decreased (-21%; P < 0.01), and muscle architecture was altered, as shown by a decrease in fascicle length (-15%; P < 0.05) and a decreasing trend in muscle thickness (-8%; P = 0.08). We demonstrated both IMAT development and muscle atrophy in patients with breast cancer who were treated with chemotherapy. FAPs, critical stem cells inducing both IMAT development and skeletal muscle atrophy, also increased, suggesting that FAPs likely play a critical role in the skeletal muscle deconditioning observed in patients with breast cancer who were treated with chemotherapy.

The present study aimed to investigate the effect of cold water immersion (CWI) on the recovery of neuromuscular fatigue following simulated soccer match-play. In a randomized design, twelve soccer players completed a 90-min simulated soccer match followed by either CWI or thermoneutral water immersion (TWI, sham condition). Before and after match (immediately after CWI/TWI through 72 h recovery), neuromuscular and performance assessments were performed. Maximal voluntary contraction (MVC) and twitch responses, delivered through electrical femoral nerve stimulation, were used to assess peripheral fatigue (quadriceps resting twitch force, Q tw,pot ) and central fatigue (voluntary activation, VA). Performance was assessed via squat jump (SJ), countermovement jump (CMJ), and 20 m sprint tests. Biomarkers of muscle damages (creatine kinase, CK; Lactate dehydrogenase, LDH) were also collected. Smaller reductions in CWI than TWI were found in MVC (-9.9 ± 3% vs -23.7 ± 14.7%), VA (-3.7 ± 4.9% vs -15.4 ± 5.6%) and Q tw,pot (-15.7 ± 5.9% vs . -24.8 ± 9.5%) following post-match intervention ( p < 0.05). On the other hand, smaller reductions in CWI than TWI were found only in Q tw,pot (-0.2 ± 7.7% vs . -8.8 ± 9.6%) at 72 h post-match. Afterwards, these parameters remained lower compared to baseline up to 48-72 h in TWI while they all recovered within 24 h in CWI. The 20 m sprint performance was less impaired in CWI than TWI (+11.1 ± 3.2% vs . +18 ± 3.6%, p < 0.05) while SJ and CMJ were not affected by the recovery strategy. Plasma LDH, yet no CK, were less increased during recovery in CWI compared to TWI. This study showed that CWI reduced both central and peripheral components of fatigue, which in turn led to earlier full recovery of the neuromuscular function and performance indices. Therefore, CWI might be an interesting recovery strategy for soccer players., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bouchiba, Bragazzi, Zarzissi, Turki, Zghal, Grati, Daab, Ayadi, Rebai, Ibn Hadj Amor, Hureau and Bouzid.)

Intramuscular hydrogen ion (H + ) and inorganic phosphate (Pi) concentrations were dissociated during exercise to challenge their relationships with peripheral and central fatigue in vivo. Ten recreationally active, healthy men (27 ± 5 years; 180 ± 4 cm; 76 ± 10 kg) performed two consecutive intermittent isometric single-leg knee-extensor trials (60 maximal voluntary contractions; 3 s contraction, 2 s relaxation) interspersed with 5 min of rest. Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) was used to continuously quantify intramuscular [H + ] and [Pi] during both trials. Using electrical femoral nerve stimulation, quadriceps twitch force (Q tw ) and voluntary activation (VA) were quantified at rest and throughout both trials. Decreases in Q tw and VA from baseline were used to determine peripheral and central fatigue, respectively. Q tw was strongly related to both [H + ] (β coefficient: -0.9, P < 0.0001) and [Pi] (-1.1, P < 0.0001) across trials. There was an effect of trial on the relationship between Q tw and [H + ] (-0.5, P < 0.0001), but not Q tw and [Pi] (0.0, P = 0.976). This suggests that, unlike the unaltered association with [Pi], a given level of peripheral fatigue was associated with a different [H + ] in Trial 1 vs. Trial 2. VA was related to [H + ] (-0.3, P < 0.0001), but not [Pi] (-0.2, P = 0.243), across trials and there was no effect of trial (-0.1, P = 0.483). Taken together, these results support intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents in the interstitial space, as a contributor to central fatigue during exercise. KEY POINTS: We investigated the relationship between intramuscular metabolites and neuromuscular function in humans performing two maximal, intermittent, knee-extension trials interspersed with 5 min of rest. Concomitant measurements of intramuscular hydrogen (H + ) and inorganic phosphate (Pi) concentrations, as well as quadriceps twitch-force (Q tw ) and voluntary activation (VA), were made throughout each trial using phosphorus magnetic resonance spectroscopy ( 31 P-MRS) and electrical femoral nerve stimulations. Although [Pi] fully recovered prior to the onset of the second trial, [H + ] did not. Q tw was strongly related to both [H + ] and [Pi] across both trials. However, the relationship between Q tw and [H + ] shifted leftward from the first to the second trial, whereas the relationship between Q tw and [Pi] remained unaltered. VA was related to [H + ], but not [Pi], across both trials. These in vivo findings support the hypotheses of intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents, as a contributor to central fatigue., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

Background: Chemotherapy is extensively used to treat breast cancer and is associated with skeletal muscle deconditioning, which is known to reduce patients' quality of life, treatment efficiency, and overall survival. To date, skeletal muscle mitochondrial alterations represent a major aspect explored in breast cancer patients; nevertheless, the cellular mechanisms remain relatively unknown. This study was dedicated to investigating overall skeletal muscle mitochondrial homeostasis in early breast cancer patients undergoing chemotherapy, including mitochondrial quantity, function, and dynamics., Methods: Women undergoing (neo)adjuvant anthracycline-cyclophosphamide and taxane-based chemotherapy participated in this study (56 ± 12 years). Two muscle biopsies were collected from the vastus lateralis muscle before the first and after the last chemotherapy administration. Mitochondrial respiratory capacity, reactive oxygen species production, and western blotting analyses were performed., Results: Among the 11 patients, we found a decrease in key markers of mitochondrial quantity, reaching -52.0% for citrate synthase protein levels (P = 0.02) and -38.2% for VDAC protein levels (P = 0.04). This mitochondrial content loss is likely explained by reduced mitochondrial biogenesis, as evidenced by a decrease in PGC-1α1 protein levels (-29.5%; P = 0.04). Mitochondrial dynamics were altered, as documented by a decrease in MFN2 protein expression (-33.4%; P = 0.01), a key marker of mitochondrial outer membrane fusion. Mitochondrial fission is a prerequisite for mitophagy activation, and no variation was found in either key markers of mitochondrial fission (Fis1 and DRP1) or mitophagy (Parkin, PINK1, and Mul1). Two contradictory hypotheses arise from these results: defective mitophagy, which probably increases the number of damaged and fragmented mitochondria, or a relative increase in mitophagy through elevated mitophagic potential (Parkin/VDAC ratio; +176.4%; P < 0.02). Despite no change in mitochondrial respiratory capacity and COX IV protein levels, we found an elevation in H 2 O 2 production (P < 0.05 for all substrate additions) without change in antioxidant enzymes. We investigated the apoptosis pathway and found an increase in the protein expression of the apoptosis initiation marker Bax (+72.0%; P = 0.04), without variation in the anti-apoptotic protein Bcl-2., Conclusions: This study demonstrated major mitochondrial alterations subsequent to chemotherapy in early breast cancer patients: (i) a striking reduction in mitochondrial biogenesis, (ii) altered mitochondrial dynamics and potential mitophagy defects, (iii) exacerbated H 2 O 2 production, and (iv) increased initiation of apoptosis. All of these alterations likely explain, at least in part, the high prevalence of skeletal muscle and cardiorespiratory deconditioning classically observed in breast cancer patients., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

This study examined the impact of aging on the elastic and resistive components of the work of breathing ( W b ) during locomotor exercise at a given 1 ) ventilatory rate, 2 ) metabolic rate, and 3 ) operating lung volume. Eight healthy younger (25 ± 4 yr) and 8 older (72 ± 6 yr) participants performed incremental bicycle exercise, from which retrospective analyses identified similar ventilatory rates (approximately 40, 70, and 100 L·min -1 ), similar metabolic rates (V̇o 2 : approximately 1.2, 1.6, and 1.9 L·min -1 ), and similar lung volumes [inspiratory and expiratory reserve volumes (IRV/ERV: approximately 25/34%, 16/33%, and 13-34% of vital capacity]. W b at each level was quantified by integrating the averaged esophageal pressure-volume loop, which was then partitioned into elastic and resistive components of inspiratory and expiratory work using the modified Campbell diagram. IRV was smaller in the older participants during exercise at ventilations of 70 and 100 L·min -1 and during exercise at the three metabolic rates ( P < 0.05). Mainly because of a greater inspiratory elastic and resistive W b in the older group ( P < 0.05), total W b was augmented by 40%-50% during exercise at matched ventilatory and matched metabolic rates. When examined during exercise evoking similar lung volumes, total W b was not different between the groups ( P = 0.86). Taken together, although aging exaggerates total W b during locomotor exercise at a given ventilatory or a given metabolic rate, this difference is abolished during exercise at a given operating lung volume. These findings highlight the significance of operating lung volume in determining the age-related difference in W b during locomotor exercise. NEW & NOTEWORTHY This study evaluated the impact of aging on the work of breathing ( W b ) during locomotor exercise evoking similar ventilatory rates, metabolic rates, and operating lung volumes in young and older individuals. Mainly because of a greater inspiratory elastic and resistive W b in older participants, total W b was higher during exercise at any given ventilatory and metabolic rate with aging. However, this age-related difference was abolished during exercise evoking similar operating lung volumes in both age groups. These findings highlight the significance of lung volumes in determining the age-related difference in total W b .

Purpose: This study aimed to determine the contribution of metabolic, cardiopulmonary, neuromuscular, and biomechanical factors to the energy cost (ECR) of graded running in well-trained runners., Methods: Eight men who were well-trained trail runners (age: 29 [10] y, mean [SD]; maximum oxygen consumption: 68.0 [6.4] mL·min-1·kg-1) completed maximal isometric evaluations of lower limb extensor muscles and 3 randomized trials on a treadmill to determine their metabolic and cardiovascular responses and running gait kinematics during downhill (DR: -15% slope), level (0%), and uphill running (UR: 15%) performed at similar O2 uptake (approximately 60% maximum oxygen consumption)., Results: Despite similar O2 demand, ECR was lower in DR versus level running versus UR (2.5 [0.2] vs 3.6 [0.2] vs 7.9 [0.5] J·kg-1·m-1, respectively; all P < .001). Energy cost of running was correlated between DR and level running conditions only (r2 = .63; P = .018). Importantly, while ECR was correlated with heart rate, cardiac output, and arteriovenous O2 difference in UR (all r2 > .50; P < .05), ECR was correlated with lower limb vertical stiffness, ground contact time, stride length, and step frequency in DR (all r2 > .58; P < .05). Lower limb isometric extension torques were not related to ECR whatever the slope., Conclusion: The determining physiological factors of ECR might be slope specific, mainly metabolic and cardiovascular in UR versus mainly neuromuscular and mechanical in DR. This possible slope specificity of ECR during incline running opens the way for the implementation of differentiated physiological evaluations and training strategies to optimize performance in well-trained trail runners.

This study investigated the impact of dietary nitrate supplementation on peripheral hemodynamics, the development of neuromuscular fatigue, and time to task failure during cycling exercise. Eleven recreationally active male participants (27 ± 5 yr, V̇o 2max : 42 ± 2 mL/kg/min) performed two experimental trials following 3 days of either dietary nitrate-rich beetroot juice (4.1 mmol NO 3 - /day; DNS) or placebo (PLA) supplementation in a blinded, counterbalanced order. Exercise consisted of constant-load cycling at 50, 75, and 100 W (4 min each) and, at ∼80% of peak power output (218 ± 12 W), to task-failure. All participants returned to repeat the shorter of the two trials performed to task failure, but with the opposite supplementation regime (iso-time comparison; ISO). Mean arterial pressure (MAP), leg blood flow (Q L ; Doppler ultrasound), leg vascular conductance (LVC), and pulmonary gas exchange were continuously assessed during exercise. Locomotor muscle fatigue was determined by the change in pre to postexercise quadriceps twitch-torque (ΔQ tw ) and voluntary activation (ΔVA; electrical femoral nerve stimulation). Following DNS, plasma [nitrite] (∼670 vs. ∼180 nmol) and [nitrate] (∼775 vs. ∼11 μmol) were significantly elevated compared with PLA. Unlike PLA, DNS lowered both Q L and MAP by ∼8% ( P < 0.05), but did not alter LVC ( P = 0.31). V̇O 2 across work rates, as well as cycling time to task-failure (∼7 min) and locomotor muscle fatigue following the ISO-time comparison were not different between the two conditions (ΔQ tw ∼42%, ΔVA ∼4%). Thus, despite significant hemodynamic changes, DNS did not alter the development of locomotor muscle fatigue and, ultimately, cycling time to task failure. NEW & NOTEWORTHY This study sought to characterize the impact of dietary nitrate supplementation on the hemodynamic response, locomotor muscle fatigue, and time to task failure during cycling exercise. Although nitrate supplementation lowered mean arterial pressure and exercising leg blood flow, leg vascular conductance and oxygen utilization were unaffected. Despite significant hemodynamic changes, there was no effect of dietary nitrate on neuromuscular fatigue development and, ultimately, cycling time to task failure.

Recently it was documented that fatiguing, high-intensity exercise resulted in a significant attenuation in maximal skeletal muscle mitochondrial respiratory capacity, potentially due to the intramuscular metabolic perturbation elicited by such intense exercise. With the utilization of intrathecal fentanyl to attenuate afferent feedback from group III/IV muscle afferents, permitting increased muscle activation and greater intramuscular metabolic disturbance, this study aimed to better elucidate the role of metabolic perturbation on mitochondrial respiratory function. Eight young, healthy males performed high-intensity cycle exercise in control (CTRL) and fentanyl-treated (FENT) conditions. Liquid chromatography-mass spectrometry and high-resolution respirometry were used to assess metabolites and mitochondrial respiratory function, respectively, pre- and postexercise in muscle biopsies from the vastus lateralis. Compared with CTRL, FENT yielded a significantly greater exercise-induced metabolic perturbation (PCr: -67% vs. -82%, Pi: 353% vs. 534%, pH: -0.22 vs. -0.31, lactate: 820% vs. 1,160%). Somewhat surprisingly, despite this greater metabolic perturbation in FENT compared with CTRL, with the only exception of respiratory control ratio (RCR) (-3% and -36%) for which the impact of FENT was significantly greater, the degree of attenuated mitochondrial respiratory capacity postexercise was not different between CTRL and FENT, respectively, as assessed by maximal respiratory flux through complex I (-15% and -33%), complex II (-36% and -23%), complex I + II (-31% and -20%), and state 3 CI+CII control ratio (-24% and -39%). Although a basement effect cannot be ruled out, this failure of an augmented metabolic perturbation to extensively further attenuate mitochondrial function questions the direct role of high-intensity exercise-induced metabolite accumulation in this postexercise response.

Breast cancer represents the most commonly diagnosed cancer while neoadjuvant and adjuvant chemotherapies are extensively used in order to reduce tumor development and improve disease-free survival. However, chemotherapy also leads to severe off-target side-effects resulting, together with the tumor itself, in major skeletal muscle deconditioning. This review first focuses on recent advances in both macroscopic changes and cellular mechanisms implicated in skeletal muscle deconditioning of breast cancer patients, particularly as a consequence of the chemotherapy treatment. To date, only six clinical studies used muscle biopsies in breast cancer patients and highlighted several important aspects of muscle deconditioning such as a decrease in muscle fibers cross-sectional area, a dysregulation of protein turnover balance and mitochondrial alterations. However, in comparison with the knowledge accumulated through decades of intensive research with many different animal and human models of muscle atrophy, more studies are necessary to obtain a comprehensive understanding of the cellular processes implicated in breast cancer-mediated muscle deconditioning. This understanding is indeed essential to ultimately lead to the implementation of efficient preventive strategies such as exercise, nutrition or pharmacological treatments. We therefore also discuss potential mechanisms implicated in muscle deconditioning by drawing a parallel with other cancer cachexia models of muscle wasting, both at the pre-clinical and clinical levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mallard, Hucteau, Hureau and Pagano.)

Introduction: We determined the recovery from neuromuscular fatigue in six professional (PRO) and seven moderately trained (MOD) cyclists after repeated cycling time trials of various intensities/durations., Method: Participants performed two 1-min (1minTT) or two 10-min (10minTT) self-paced cycling time trials with 5 min of recovery in between. Central and peripheral fatigue were quantified via preexercise to postexercise (15-s through 15-min recovery) changes in voluntary activation (VA) and potentiated twitch force. VA was measured using the interpolated twitch technique, and potentiated twitch force was evoked by single (QTsingle) and paired (10-Hz (QT10) and 100-Hz (QT100)) electrical stimulations of the femoral nerve., Results: Mean power output was 32%-72% higher during all the time trials and decreased less (-10% vs -13%) from the first to second time trial in PRO compared with MOD (P < 0.05). Conversely, exercise-induced reduction in QTsingle and QT10/QT100 was significantly lower in PRO after every time trial (P < 0.05). Recovery from fatigue from 15 s to 2 min for QTsingle and QT10/QT100 was slower in PRO after every time trial (P < 0.05). In both groups, the reduction in QTsingle was lower after the 10minTTs compared with 1minTTs (P < 0.05). Conversely, VA decreased more after the 10minTTs compared with 1minTTs (P < 0.05)., Conclusion: Our findings showed that excitation-contraction coupling was preserved after exercise in PRO compared with MOD. This likely contributed to the improved performance during repeated cycling time trials of various intensity/duration in PRO, despite a slower rate of recovery in its early phase. Finally, the time course of recovery from neuromuscular fatigue in PRO was dependent on the effects of prolonged low-frequency force depression., (Copyright © 2020 by the American College of Sports Medicine.)

This study explores the cardiorespiratory and muscular fatigue responses to downhill (DR) vs uphill running (UR) at similar running speed or similar oxygen uptake (⩒O 2 ). Eight well-trained, male, trail runners completed a maximal level incremental test and three 15-min treadmill running trials at ±15% slope: i) DR at ~6 km·h -1 and ~19% ⩒O 2max (LDR); ii) UR at ~6 km·h -1 and ~70% ⩒O 2max (HUR); iii) DR at ~19 km·h -1 and ~70% ⩒O 2max (HDR). Cardiorespiratory responses and spatiotemporal gait parameters were measured continuously. Maximal isometric torque was assessed before and after each trial for hip and knee extensors and plantar flexor muscles. At similar speed (~6 km·h -1 ), cardiorespiratory responses were attenuated in LDR vs HUR with altered running kinematics (all p < 0.05). At similar ⩒O 2 (~3 l·min -1 ), heart rate, pulmonary ventilation and breathing frequency were exacerbated in HDR vs HUR ( p < 0.01), with reduced torque in knee (-15%) and hip (-11%) extensors and altered spatiotemporal gait parameters (all p < 0.01). Despite submaximal metabolic intensity (70% ⩒O 2max ), heart rate and respiratory frequency reached maximal values in HDR. These results further our understanding of the particular cardiorespiratory and muscular fatigue responses to DR and provide the bases for future DR training programs for trail runners.

Purpose: The purpose of this study was to investigate the influence of the soccer pitch area during small-sided games (SSG) in prepubertal children on physiological and technical demands, and to compare them, for the physiological demands, to high-intensity interval training (HIIT)., Methods: Ten young soccer players (13.0 [0.3] y) performed a HIIT and 3 SSG of various field sizes (30 × 20 m, 42 × 38 m, and 51 × 34 m). Each SSG was performed with 5 players per team, during 4 × 4-minutes interspaced with 1 minute of passive recovery in between. HIIT also followed a 4 × 4-minute protocol with running speed set on an individual basis. Heart rate (HR) was continuously monitored during training sessions. For each exercise modality, time spent above 90% of HRmax (T≥90%,HRmax) was calculated, and technical actions were quantified during SSG by video analysis., Results: T≥90%,HRmax was similar between the 3 SSG (∼587 [276] s; P > .2) but 24% to 37% lower than during HIIT (826 [140] s, P < .05). Coefficients of variations in T≥90%,HRmax were 2.3 to 3.5 times larger in SSG compared with HIIT. For technical actions, greater number of possessions (21 [6] vs ∼14 [4]), and lower ball touches per possession (2.4 [0.6] vs ∼2.9 [0.6]) were found in the small SSG compared with larger SSG, respectively (P < .05)., Conclusion: The 3 SSG led to lower acute stimulation of the aerobic metabolism, suggesting a lower potential for chronic aerobic adaptations, compared with HIIT. Moreover, interindividual variability in the physiological response was substantially greater in SSG compared with HIIT, indicating increased heterogeneity among players performing the same training protocol.

Objectives: Recent studies investigated the determinants of trail running performance (i.e., combining uphill (UR) and downhill running sections (DR)), while the possible specific physiological factors specifically determining UR vs DR performances (i.e., isolating UR and DR) remain presently unknown. This study aims to determine the cardiorespiratory responses to outdoor DR vs UR time-trial and explore the determinants of DR and UR performance in highly trained runners., Design: Randomized controlled trial., Methods: Ten male highly-trained endurance athletes completed 5-km DR and UR time-trials (average grade: ±8%) and were tested for maximal oxygen uptake, lower limb extensor maximal strength, local muscle endurance, leg musculotendinous stiffness, vertical jump ability, explosivity/agility and sprint velocity. Predictors of DR and UR performance were investigated using correlation and commonality regression analyses., Results: Running velocity was higher in DR vs UR time-trial (20.4±1.0 vs 12.0±0.5km·h -1 , p<0.05) with similar average heart rate (95±2% vs 94±2% maximal heart rate; p>0.05) despite lower average V̇O 2 (85±8% vs 89±7% V̇O 2max ; p<0.05). Velocity at V̇O 2max (vV̇O 2max ) body mass index (BMI) and maximal extensor strength were significant predictors of UR performance (r 2 =0.94) whereas vV̇O 2max , leg musculotendinous stiffness and maximal extensor strength were significant predictors of DR performance (r 2 =0.84)., Conclusions: Five-km UR and DR running performances are both well explained by three independent predictors. If two predictors are shared between UR and DR performances (vV̇O 2max and maximal strength), their relative contribution is different and, importantly, the third predictor appears very specific to the exercise modality (BMI for UR vs leg musculotendinous stiffness for DR)., (Copyright © 2020 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

We examined the effect of intravenous ascorbate (VitC) administration on exercise-induced redox balance, inflammation, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Eight COPD patients completed constant-load cycling (∼80% of peak power output, 83 ± 10 W) to task failure after intravenous VitC (2 g) or saline (placebo, PL) infusion. All participants repeated the shorter of the two exercise trials (isotime) with the other infusate. Quadriceps fatigue was determined by pre- to postexercise changes in quadriceps twitch torque (ΔQ tw , electrical femoral nerve stimulation). Corticospinal excitability before, during, and after exercise was assessed by changes in motor evoked potentials triggered by transcranial magnetic stimulation. VitC increased superoxide dismutase (marker for endogenous antioxidant capacity) by 129% and mitigated C-reactive protein (marker for inflammation) in the plasma during exercise but failed to alter the exercise-induced increase in lipid peroxidation (malondialdehyde) and free radicals [electron paramagnetic resonance (EPR)-spectroscopy]. Although VitC did, indeed, decrease neuromuscular fatigue (ΔQ tw : PL -29 ± 5%, VitC -23 ± 6%, P < 0.05), there was no impact on corticospinal excitability and time to task failure (∼8 min, P = 0.8). Interestingly, in terms of pulmonary limitations to exercise, VitC had no effect on perceived exertional dyspnea (∼8.5/10) and its determinants, including oxygen saturation ([Formula: see text]) (∼92%) and respiratory muscle work (∼650 cmH 2 O·s·min -1 ) ( P > 0.3). Thus, although VitC facilitated indicators for antioxidant capacity, diminished inflammatory markers, and improved neuromuscular fatigue resistance, it failed to improve exertional dyspnea and cycling exercise tolerance in patients with COPD. As dyspnea is recognized to limit exercise tolerance in COPD, the otherwise beneficial effects of VitC may have been impacted by this unaltered sensation. NEW & NOTEWORTHY We investigated the effect of intravenous vitamin C on redox balance, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Acute vitamin C administration increased superoxide dismutase (marker of antioxidant capacity) and attenuated fatigue development but failed to improve exertional dyspnea and exercise tolerance. These findings suggest that a compromised redox balance plays a critical role in the development of fatigue in COPD but also highlight the significance of exertional dyspnea as an important symptom limiting the patients' exercise tolerance.

This study investigated the impact of HFpEF on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (NYHA II-III, ejection-fraction: 61 ± 2%) and eight healthy controls performed dynamic knee extension exercise (80% peak workload) to task failure and maximal intermittent quadriceps contractions (8 × 15 s). Controls repeated knee extension at the same absolute intensity as HFpEF. Leg blood flow (Q L ) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQ tw ; peripheral fatigue), voluntary activation (ΔVA; central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24 ± 5 W) and controls (42 ± 6 W) had a similar time-to-task failure (∼10 min), ΔQ tw (∼50%), and ΔVA (∼6%). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower Q L response time. Knee extension exercise at the same absolute intensity resulted in an ∼40% lower Q L and greater ΔQ tw and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQ tw was larger in HFpEF versus controls during isometric exercise. In conclusion, HFpEF patients are characterized by a similar development of central and peripheral fatigue as healthy controls when tested at the same relative intensity during exercise not limited by cardiac output. However, HFpEF patients have a greater susceptibility to neuromuscular fatigue during exercise at a given absolute intensity, and this impairs functional capacity. The patients' compromised Q L response to exercise likely accounts, at least partly, for the patients' attenuated fatigue resistance. NEW & NOTEWORTHY The susceptibility to neuromuscular fatigue during exercise is substantially exaggerated in individuals with heart failure with a preserved ejection fraction. The faster rate of fatigue development is associated with the compromised peripheral hemodynamic response characterizing these patients during exercise. Given the role of neuromuscular fatigue as a factor limiting exercise, this impairment likely accounts for a significant portion of the exercise intolerance typical for this population.

The aim of the present study was to determine the magnitude of the maximal level of peripheral fatigue attainable (fatigue threshold) during an all-out intermittent isometric knee-extensor protocol in both younger (24 ± 1 yr, n = 12) and older (60 ± 2 yr, n = 12) participants to provide new insights into the effects of aging on neuromuscular function. Participants performed two experimental sessions, in which they performed 60 maximal voluntary contractions (MVCs; 3 s of contraction, 2 s of relaxation). One trial was performed in the unfatigued state (CTRL) and one other following fatiguing neuromuscular electrical stimulation of the quadriceps (F NMES ). Peripheral fatigue was quantified via pre/postexercise decrease in quadriceps twitch force (∆P tw ). Critical force (CF) was determined as the mean force output of the last 12 contractions, whereas W ' was calculated as the area above CF. Although F NMES led to a significant decrease in P tw before performing the 60-MVCs protocol ( P = 0.024), ∆P tw was not different between CTRL and F NMES for both the young group ( P = 0.491) and the old group ( P = 0.523). However, this peripheral fatigue threshold was significantly greater in young versus old participants (∆P tw  = -48 ± 10% vs. -29 ± 13%, respectively, P = 0.028). In CTRL, W' was 55 ± 13% lower in the old group than in the young group ( P < 0.001), but CF was similar (326 ± 10 N vs. 322 ± 12 N, respectively, P = 0.941). ∆P tw was correlated with W' , independently of age ( r 2  = 0.84, P < 0.001). Exercise performance decreases with aging consequent to a lower tolerance to peripheral fatigue. However, the peripheral fatigue threshold mechanism persists with healthy aging and continues to play a protective role in preserving locomotor muscle function during exercise.

Maximal strength training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria are still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo 31P magnetic resonance spectroscopy (31P-MRS), and gas exchange. As anticipated, MST resulted in an increased isometric knee-extensor force from 133 ± 36 to 147 ± 49 Nm (p < .05) and quadriceps muscle volume from 1,410 ± 103 to 1,555 ± 455 cm3 (p < .05). Mitochondrial complex (I-V) protein abundance and citrate synthase activity were not significantly altered by MST. Assessed ex vivo, maximal ADP-stimulated respiration (state 3CI+CII, PRE: 23 ± 6 and POST: 14 ± 5 ρM·mg-1·s-1, p < .05), was decreased by MST, predominantly, as a result of a decline in complex I-linked respiration (p < .05). Additionally, state 3 free-fatty acid linked respiration was decreased following MST (PRE: 19 ± 5 and POST: 14 ± 3 ρM·mg-1·s-1, p < .05). Assessed in vivo, MST slowed the PCr recovery time constant (PRE: 49 ± 13 and POST: 57 ± 16 seconds, p < .05) and lowered, by ~20% (p = .055), the quadriceps peak rate of oxidative ATP synthesis, but did not significantly alter the oxidation of lipid. Although these, likely qualitative, mitochondrial adaptations are potentially negative in terms of skeletal muscle energetic capacity, they need to be considered in light of the many improvements in muscle function that MST affords older adults., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of the present study was to investigate the existence of a critical threshold beyond which peripheral fatigue would not further decrease during knee extensor (KE) exercise in older men, and the consequences of this mechanism on the force-duration relationship. Twelve old men (59 ± 2 years) randomly performed two different sessions, in which they performed 60 maximum voluntary contractions (MVC; 3s contraction, 2s relaxation). One trial was performed in the unfatigued state (CTRL) and one other following fatiguing neuromuscular electrical stimulation of the KE (F NMES ). Peripheral and central fatigue were quantified via pre/post-exercise decreases in quadriceps twitch-force (Δ P tw ) and voluntary activation (ΔVA). Critical torque (CT) was determined as the mean force of the last 12 contractions while W' was calculated as the area above CT. Compared with CTRL, pre-fatigue (Δ P tw  = -10.3 ± 6.2%) resulted in a significant ( p  < 0.05) reduction in W' (-18.2 ± 1.6%) in F NMES . However, CT (∼964 N), ΔVA (∼15%) and Δ P tw (∼25%) post-MVCs were similar between both conditions. In CTRL, W' was correlated with Δ P tw ( r 2  = 0.78). Moreover, the difference in W' between CTRL and F NMES was correlated with the level of pre-fatigue induced in F NMES ( r 2  = 0.76). These findings document that peripheral fatigue is confined to an individual threshold during KE exercise in older men. Furthermore, correlative results suggest that mechanisms regulating peripheral fatigue to a critical threshold also restrict W', and therefore play a role in exercise capacity in older men.

Key Points: Although the exercise pressor reflex (EPR) and the chemoreflex (CR) are recognized for their sympathoexcitatory effect, the cardiovascular implication of their interaction remains elusive. We quantified the individual and interactive cardiovascular consequences of these reflexes during exercise and revealed various modes of interaction. The EPR and hypoxia-induced CR interaction is hyper-additive for blood pressure and heart rate (responses during co-activation of the two reflexes are greater than the summation of the responses evoked by each reflex) and hypo-additive for peripheral haemodynamics (responses during co-activation of the reflexes are smaller than the summated responses). The EPR and hypercapnia-induced CR interaction results in a simple addition of the individual responses to each reflex (i.e. additive interaction). Collectively, EPR:CR co-activation results in significant cardiovascular interactions with restriction in peripheral haemodynamics, resulting from the EPR:CR interaction in hypoxia, likely having the most crucial impact on the functional capacity of an exercising human., Abstract: We investigated the interactive effect of the exercise pressor reflex (EPR) and the chemoreflex (CR) on the cardiovascular response to exercise. Eleven healthy participants (5 females) completed a total of six bouts of single-leg knee-extension exercise (60% peak work rate, 4 min each) either with or without lumbar intrathecal fentanyl to attenuate group III/IV afferent feedback from lower limbs to modify the EPR, while breathing either ambient air, normocapnic hypoxia (S a O 2 ∼79%, P a O 2 ∼43 mmHg, P a CO 2 ∼33 mmHg, pH ∼7.39), or normoxic hypercapnia (S a O 2 ∼98%, P a O 2 ∼105 mmHg, P a CO 2 ∼50 mmHg, pH ∼7.26) to modify the CR. During co-activation of the EPR and the hypoxia-induced CR (O 2 -CR), mean arterial pressure and heart rate were significantly greater, whereas leg blood flow and leg vascular conductance were significantly lower than the summation of the responses evoked by each reflex alone. During co-activation of the EPR and the hypercapnia-induced CR (CO 2 -CR), the haemodynamic responses were not different from the summated responses to each reflex response alone (P ≥ 0.1). Therefore, while the interaction resulting from the EPR:O 2 -CR co-activation is hyper-additive for blood pressure and heart rate, and hypo-additive for peripheral haemodynamics, the interaction resulting from the EPR:CO 2 -CR co-activation is simply additive for all cardiovascular parameters. Thus, EPR:CR co-activation results in significant interactions between cardiovascular reflexes, with the impact differing when the CR activation is achieved by hypoxia or hypercapnia. Since the EPR:CR co-activation with hypoxia potentiates the pressor response and restricts blood flow to contracting muscles, this interaction entails the most functional impact on an exercising human., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Purpose: The purpose of this study was twofold: (i) determine if well-trained athletes can achieve similar peak oxygen uptake (V˙O2peak) in downhill running (DR) versus level running (LR) or uphill running (UR) and (ii) investigate if lower limb extensor muscle strength is related to the velocity at V˙O2peak (vV˙O2peak) in DR, LR, and UR., Methods: Eight athletes (V˙O2max = 68 ± 2 mL·min·kg) completed maximal incremental tests in LR, DR (-15% slope), and UR (+15% slope) on a treadmill (+1, +1.5, and +0.5 km·h every 2 min, respectively) while cardiorespiratory responses and spatiotemporal running parameters were continuously measured. They were also tested for maximal voluntary isometric strength of hip and knee extensors and plantar flexors., Results: Oxygen uptake at maximal effort was approximately 16% to 18% lower in DR versus LR and UR (~57 ± 2 mL·min·kg, 68 ± 2 mL·min·kg, and 70 ± 3 mL·min·kg, respectively) despite much greater vV˙O2peak (22.7 ± 0.6 km·h vs 18.7 ± 0.5 km·h and 9.3 ± 0.3 km·h, respectively). At vV˙O2peak, longer stride length and shorter contact time occurred in DR versus LR and UR (+12%, +119%, -38%, and -61%, respectively). Contrary to knee extensor and plantar flexor, hip extensor isometric strength correlated to vV˙O2peak in DR, LR, and UR (r = -0.86 to -0.96, P < 0.05). At similar V˙O2, higher heart rate and ventilation emerged in DR versus LR and UR, associated with a more superficial ventilation pattern., Conclusions: This study demonstrates that well-trained endurance athletes, accustomed to DR, achieved lower V˙O2peak despite higher vV˙O2peak during DR versus LR or UR maximal incremental tests. The specific heart rate and ventilation responses in DR might originate from altered running gait and increased lower-limb musculotendinous mechanical loading, furthering our understanding of the particular physiology of DR, ultimately contributing to optimize trail race running performance.

Context: Drop jumps and high-intensity interval running are relevant training methods to improve explosiveness and endurance performance, respectively. Combined training effects might, however, be achieved by performing interval drop jumping., Purpose: To determine the acute effects of interval drop jumping on oxygen uptake (V˙O2)-index of cardioventilatory/oxidative stimulation level and peripheral fatigue-a limiting factor of explosiveness., Methods: Thirteen participants performed three 11-minute interval training sessions during which they ran 15 seconds at 120% of the velocity that elicited maximal V˙O2 (V˙O2max) (ITrun), or drop jumped at 7 (ITDJ7) or 9 (ITDJ9) jumps per 15 seconds, interspersed with 15 seconds of passive recovery. V˙O2 and the time spent above 90% of V˙O2max (V˙TO2max) were collected. Peripheral fatigue was quantified via preexercise to postexercise changes in evoked potentiated quadriceps twitch (ΔQT). Power output was estimated during ITDJs using optical sensors., Results: All participants reached 90% of V˙O2max or higher during ITrun and ITDJ9, but only 11 did during ITDJ7. V˙TO2max was not different between ITrun and ITDJ9 (145 [76] vs 141 [151] s; P = .92) but was reduced during ITDJ7 (28 [26] s; P = .002). Mean ΔQT in ITDJ9 and ITDJ7 was not different (-17% [9%] vs -14% [8%]; P = .73) and greater than in ITrun (-8% [7%]; P = .001). No alteration in power output was found during ITDJs (37 [10] W·kg-1)., Conclusion: Interval drop jumping at a high work rate stimulated the cardioventilatory and oxidative systems to the same extent as interval running, while the exercise-induced increase in fatigue did not compromise drop jump performance. Interval drop jumping might be a relevant strategy to get concomitant improvements in endurance and explosive performance.

We sought to investigate the role of group III/IV muscle afferents in limiting endurance exercise performance, independently of their role in optimizing locomotor muscle O 2 delivery. While breathing 100% O 2 to ensure a similar arterial O 2 content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (H CTRL ) and with lumbar intrathecal fentanyl (H FENT ) impairing neural feedback from the lower limbs. After each time trial, common femoral artery blood flow (FBF) was quantified (Doppler ultrasound) during constant-load cycling performed at the average power of the preceding time trial. The assessment of end-tidal gases, hemoglobin content and saturation, and FBF facilitated the calculation of leg O 2 delivery. Locomotor muscle activation during cycling was estimated from vastus lateralis EMG. With electrical femoral nerve stimulation, peripheral and central fatigue were quantified by pre- to postexercise decreases in quadriceps twitch torque (ΔQ tw ) and voluntary activation (ΔVA), respectively. FBF (~16 mL·min -1 ·W -1 ; P = 0.6), [Formula: see text] (~24 mL O 2 /dL; P = 0.9), and leg O 2 delivery (~0.38 mL O 2 ·min -1 ·W -1 ; P = 0.9) were not different during H CTRL and H FENT . Mean power output and time to completion were significantly improved by 9% (~310 W vs. ~288 W) and 3% (~479 s vs. ~463 s), respectively, during H FENT compared with H CTRL . Quadriceps muscle activation was 9 ± 7% higher during H FENT compared with H CTRL ( P < 0.05). ΔQ tw was significantly greater in H FENT compared with H CTRL (54 ± 8% vs. 39 ± 9%), whereas ΔVA was not different (~5%; P = 0.3) in both trials. These findings reveal that group III/IV muscle afferent feedback limits whole body endurance exercise performance and peripheral fatigue by restricting neural activation of locomotor muscle. NEW & NOTEWORTHY Group III/IV muscle afferent feedback facilitates endurance performance by optimizing locomotor muscle O 2 delivery but also limits performance by restricting neural drive to locomotor muscle. To isolate the performance-limiting effect of these sensory neurons, we pharmacologically attenuated their central projection during a cycling time trial while controlling for locomotor muscle O 2 delivery. With no difference in leg O 2 delivery, afferent blockade attenuated the centrally mediated restriction in motoneuronal output and improved cycling performance.

Purpose: The effect of an acute bout of exercise, especially high-intensity exercise, on the function of mitochondrial respiratory complexes is not well understood, with potential implications for both the healthy population and patients undergoing exercise-based rehabilitation. Therefore, this study sought to comprehensively examine respiratory flux through the different complexes of the electron transport chain in skeletal muscle mitochondria before and immediately after high-intensity aerobic exercise., Methods: Muscle biopsies of the vastus lateralis were obtained at baseline and immediately after a 5-km time trial performed on a cycle ergometer. Mitochondrial respiratory flux through the complexes of the electron transport chain was measured in permeabilized skeletal muscle fibers by high-resolution respirometry., Results: Complex I + II state 3 (state 3CI + CII) respiration, a measure of oxidative phosphorylation capacity, was diminished immediately after the exercise (pre, 27 ± 3 ρm·mg·s; post, 17 ± 2 ρm·mg·s; P < 0.05). This decreased oxidative phosphorylation capacity was predominantly the consequence of attenuated complex II-driven state 3 (state 3CII) respiration (pre, 17 ± 1 ρm·mg·s; post, 9 ± 2 ρm·mg·s; P < 0.05). Although complex I-driven state 3 (3CI) respiration was also lower (pre, 20 ± 2 ρm·mg·s; post, 14 ± 4 ρm·mg·s), this did not reach statistical significance (P = 0.27). In contrast, citrate synthase activity, proton leak (state 2 respiration), and complex IV capacity were not significantly altered immediately after the exercise., Conclusions: These findings reveal that acute high-intensity aerobic exercise significantly inhibits skeletal muscle state 3CII and oxidative phosphorylation capacity. This, likely transient, mitochondrial defect might amplify the exercise-induced development of fatigue and play an important role in initiating exercise-induced mitochondrial adaptations.

Aging is associated with a progressive decline in skeletal muscle function, then leading to impaired exercise tolerance. Maximal strength training (MST) appears to be a practical and effective intervention to increase both exercise capacity and efficiency. However, the underlying physiological mechanisms responsible for these functional improvements are still unclear. Accordingly, the purpose of this study was to examine the intramuscular and metabolic adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older individuals (75 ± 9 yrs) by employing a combination of molecular, magnetic resonance 1 H-imaging and 31 P-spectroscopy, muscle biopsies, motor nerve stimulation, and indirect calorimetry techniques. Dynamic and isometric muscle strength were both significantly increased by MST. The greater torque-time integral during sustained isometric maximal contraction post-MST (P = 0.002) was associated with increased rates of ATP synthesis from anaerobic glycolysis (PRE: 10 ± 7 mM·min -1 ; POST: 14 ± 7 mM·min -1 , P = 0.02) and creatine kinase reaction (PRE: 31 ± 10 mM·min -1 ; POST: 41 ± 10 mM·min -1 , P = 0.006) such that the ATP cost of contraction was not significantly altered. Expression of fast myosin heavy chain, quadriceps muscle volume, and submaximal cycling net efficiency were also increased with MST (P = 0.005; P = 0.03 and P = 0.03, respectively). Overall, MST induced a shift toward a more glycolytic muscle phenotype allowing for greater muscle force production during sustained maximal contraction. Consequently, some of the MST-induced improvements in exercise tolerance might stem from a greater anaerobic capacity to generate ATP, while the improvement in exercise efficiency appears to be independent from an alteration in the ATP cost of contraction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To examine the impact of aging on neuromuscular fatigue following cycling (CYC; large active muscle mass) and single-leg knee-extension (KE; small active muscle mass) exercise, 8 young (25 ± 4 years) and older (72 ± 6 years) participants performed CYC and KE to task failure at a given relative intensity (80% of peak power output). The young also matched CYC and KE workload and duration of the old (iso-work comparison). Peripheral and central fatigue were quantified via pre-/postexercise decreases in quadriceps twitch torque (∆Q tw , electrical femoral nerve stimulation) and voluntary activation (∆VA). Although young performed 77% and 33% more work during CYC and KE, respectively, time to task failure in both modalities was similar to the old (~9.5 min; P > 0.2). The resulting ΔQ tw was also similar between groups (CYC ~40%, KE ~55%; P > 0.3); however, ∆VA was, in both modalities, approximately double in the young (CYC ~6%, KE ~9%; P < 0.05). While causing substantial peripheral and central fatigue in both exercise modalities in the old, ∆Q tw in the iso-work comparison was not significant (CYC; P = 0.2), or ~50% lower (KE; P < 0.05) in the young, with no central fatigue in either modality ( P > 0.4). Based on iso-work comparisons, healthy aging impairs fatigue resistance during aerobic exercise. Furthermore, comparisons of fatigue following exercise at a given relative intensity mask the age-related difference observed following exercise performed at the same workload. Finally, although active muscle mass has little influence on the age-related difference in the rate of fatigue at a given relative intensity, it substantially impacts the comparison during exercise at a given absolute intensity.

Key Points: This investigation assessed the influence of group III/IV muscle afferents on small muscle mass exercise performance from a skeletal muscle bioenergetics perspective. Group III/IV muscle afferent feedback was attenuated with lumbar intrathecal fentanyl during intermittent isometric single-leg knee-extensor all-out exercise, while 31 P-MRS was used to assess skeletal muscle bioenergetics. Attenuation of group III/IV muscle afferent feedback improved exercise performance during the first minute of exercise, due to an increase in total ATP production with no change in the ATP cost of contraction. However, exercise performance was not altered during the remainder of the protocol, despite a sustained increase in total ATP production, due to an exacerbated ATP cost of contraction. These findings reveal that group III/IV muscle afferents directly limit exercise performance during small muscle mass exercise, but, due to their critical role in maintaining skeletal muscle contractile efficiency, with time, the benefit of attenuating the muscle afferents is negated., Abstract: The direct influence of group III/IV muscle afferents on exercise performance remains equivocal. Therefore, all-out intermittent isometric single-leg knee-extensor exercise and phosphorous magnetic resonance spectroscopy ( 31 P-MRS) were utilized to provide a high time resolution assessment of exercise performance and skeletal muscle bioenergetics in control conditions (CTRL) and with the attenuation of group III/IV muscle afferent feedback via lumbar intrathecal fentanyl (FENT). In both conditions, seven recreationally active men performed 60 maximal voluntary quadriceps contractions (MVC; 3 s contraction, 2 s relaxation), while knee-extensor force and 31 P-MRS were assessed during each MVC. The cumulative integrated force was significantly greater (8 ± 6%) in FENT than CTRL for the first minute of the all-out protocol, but was not significantly different for the second to fifth minutes. Total ATP production was significantly greater (16 ± 21%) in FENT than CTRL throughout the all-out exercise protocol, due to a significantly greater anaerobic ATP production (11 ± 13%) in FENT than CTRL with no significant difference in oxidative ATP production. The ATP cost of contraction was not significantly different between FENT and CTRL for the first minute of the all-out protocol, but was significantly greater (29 ± 34%) in FENT than in CTRL for the second to fifth minutes. These findings reveal that group III/IV muscle afferents directly limit exercise performance during small muscle mass exercise, but, due to their critical role in maintaining skeletal muscle contractile efficiency, with time, the benefit from muscle afferent attenuation is negated., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Key Points: We investigated the contribution of group III/IV muscle afferents to carotid baroreflex resetting during electrically evoked (no central command) and voluntary (requiring central command) isometric knee extension exercise. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive group III/IV leg muscle afferent feedback. Spontaneous carotid baroreflex control was assessed by loading and unloading the carotid baroreceptors with a variable pressure neck chamber. Group III/IV muscle afferents did not influence spontaneous carotid baroreflex responsiveness at rest or during exercise. Afferent feedback accounted for at least 50% of the exercise-induced increase in the carotid baroreflex blood pressure and heart rate operating points, adjustments that are critical for an appropriate cardiovascular response to exercise. These findings suggest that group III/IV muscle afferent feedback is, independent of central command, critical for the resetting of the carotid baroreflex blood pressure and heart rate operating points, but not for spontaneous baroreflex responsiveness., Abstract: This study sought to comprehensively investigate the role of metabolically and mechanically sensitive group III/IV muscle afferents in carotid baroreflex responsiveness and resetting during both electrically evoked (EVO, no central command) and voluntary (VOL, requiring central command) isometric single-leg knee-extension (15% of maximal voluntary contraction; MVC) exercise. Participants (n = 8) were studied under control conditions (CTRL) and following lumbar intrathecal fentanyl injection (FENT) to inhibit μ-opioid receptor-sensitive lower limb muscle afferents. Spontaneous carotid baroreflex control of mean arterial pressure (MAP) and heart rate (HR) were assessed following rapid 5 s pulses of neck pressure (NP, +40 mmHg) or suction (NS, -60 mmHg). Resting MAP (87 ± 10 mmHg) and HR (70 ± 8 bpm) were similar between CTRL and FENT conditions (P > 0.4). In terms of spontaneous carotid baroreflex responsiveness, FENT did not alter the change in MAP or HR responses to NP (+13 ± 5 mmHg, P = 0.85; +9 ± 3 bpm; P = 0.99) or NS (-13 ± 5 mmHg, P = 0.99; -24 ± 11 bpm; P = 0.49) at rest or during either exercise protocol, which were of a remarkably similar magnitude to rest. In contrast, FENT administration reduced the exercise-induced resetting of the operating point for MAP and HR during both EVO (116 ± 10 mmHg to 100 ± 15 mmHg and 93 ± 14 bpm to 82 ± 10 bpm) and VOL (107 ± 13 mmHg to 100 ± 17 mmHg and 89 ± 10 bpm to 72 ± 10 bpm) exercise bouts. Together, these findings document that group III/IV muscle afferent feedback is critical for the resetting of the carotid baroreflex MAP and HR operating points, independent of exercise-induced changes in central command, but not for spontaneous carotid baroreflex responsiveness., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Neuromuscular fatigue compromises exercise performance and is determined by central and peripheral mechanisms. Interactions between the two components of fatigue can occur via neural pathways, including feedback and feedforward processes. This brief review discusses the influence of feedback and feedforward mechanisms on exercise limitation. In terms of feedback mechanisms, particular attention is given to group III/IV sensory neurons which link limb muscle with the central nervous system. Central corollary discharge, a copy of the neural drive from the brain to the working muscles, provides a signal from the motor system to sensory systems and is considered a feedforward mechanism that might influence fatigue and consequently exercise performance. We highlight findings from studies supporting the existence of a 'critical threshold of peripheral fatigue', a previously proposed hypothesis based on the idea that a negative feedback loop operates to protect the exercising limb muscle from severe threats to homeostasis during whole-body exercise. While the threshold theory remains to be disproven within a given task, it is not generalisable across different exercise modalities. The 'sensory tolerance limit', a more theoretical concept, may address this issue and explain exercise tolerance in more global terms and across exercise modalities. The 'sensory tolerance limit' can be viewed as a negative feedback loop which accounts for the sum of all feedback (locomotor muscles, respiratory muscles, organs, and muscles not directly involved in exercise) and feedforward signals processed within the central nervous system with the purpose of regulating the intensity of exercise to ensure that voluntary activity remains tolerable.

Purpose: The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation., Methods: Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (P-MRS)., Results: The magnitude of metabolic perturbation was significantly greater in FENT compared with CTRL for [Pi] (37.8 ± 16.8 vs 28.6 ± 8.6 mM), [H2PO4] (24.3 ± 12.2 vs 17.9 ± 7.1 mM), and [ATP] (75.8% ± 17.5% vs 81.9% ± 15.8% of baseline), whereas there was no significant difference in [PCr] (4.5 ± 2.4 vs 4.4 ± 2.3 mM) or pH (6.51 ± 0.10 vs 6.54 ± 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4], and pH was significantly faster in FENT compared with CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than in CTRL, resulting in a significantly greater ATP cost of contraction (0.049 ± 0.016 vs 0.038 ± 0.010 mM·min·N)., Conclusion: Group III/IV muscle afferents not only constrain the magnitude of perturbation in intramuscular Pi, H2PO4, and ATP during small muscle mass exercise but also seem to play a role in maintaining efficient skeletal muscle contractile function in men.

Purpose: This study aimed to investigate the effect of different magnitudes of deception on performance and exercise-induced fatigue during cycling time trial., Methods: After three familiarization visits, three women and eight men performed three 5-km cycling time trials while following a simulated dynamic avatar reproducing either 100% (5K100%), 102% (5K102%), or 105% (5K105%) of the subject's previous fastest trial. Quadriceps muscle activation was quantified with surface electromyography. Fatigue was quantified by preexercise to postexercise (10 s through 15 min recovery) changes in quadriceps maximal voluntary contraction (MVC) force, potentiated twitch force evoked by electrical femoral nerve stimulation (QTSingle) and voluntary activation (VA, twitch interpolation technique)., Results: Greater quadriceps muscle activation in 5K102% versus 5K100% (12% ± 11%) was found in parallel with a 5% ± 2% and 2% ± 1% improvement in power output and completion time, respectively (P < 0.01). Exercise-induced reduction in MVC force and VA were 14% ± 19% and 28% ± 31% greater at exercise termination (at 10 s), whereas QTSingle recovery (from 10 s to 15 min) was 5% ± 5% less in 5K102% versus 5K100% (P < 0.01). No difference in performance or fatigue indices measured at exercise termination was found between 5K100% and 5K105%., Conclusions: Muscle activation and performance improvements during a deceptive cycling time trial were achieved only with a 2% magnitude of deception and were associated with a further impairment in MVC force, QTSingle recovery and VA compared to control. Performance improvement during cycling time trial with augmented deceptive feedback therefore resulted in exacerbated exercise-induced peripheral and central fatigue.

Although all-out exercise protocols are commonly used, the physiological mechanisms underlying all-out exercise performance are still unclear, and an in-depth assessment of skeletal muscle bioenergetics is lacking. Therefore, phosphorus magnetic resonance spectroscopy ( 31 P-MRS) was utilized to assess skeletal muscle bioenergetics during a 5-min all-out intermittent isometric knee-extensor protocol in eight healthy men. Metabolic perturbation, adenosine triphosphate (ATP) synthesis rates, ATP cost of contraction, and mitochondrial capacity were determined from intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (P i ), diprotonated phosphate ([Formula: see text]), and pH. Peripheral fatigue was determined by exercise-induced alterations in potentiated quadriceps twitch force (Q tw ) evoked by supramaximal electrical femoral nerve stimulation. The oxidative ATP synthesis rate (ATP OX ) attained and then maintained peak values throughout the protocol, despite an ~63% decrease in quadriceps maximal force production. ThusATP OX normalized to force production (ATP OX gain) significantly increased throughout the exercise (1st min: 0.02 ± 0.01, 5th min: 0.04 ± 0.01 mM·min -1 ·N -1 ), as did the ATP cost of contraction (1st min: 0.048 ± 0.019, 5th min: 0.052 ± 0.015 mM·min -1 ·N -1 ). Additionally, the pre- to postexercise change in Q tw (-52 ± 26%) was significantly correlated with the exercise-induced change in intramuscular pH ( r = 0.75) and [Formula: see text] concentration ( r = 0.77). In conclusion, the all-out exercise protocol utilized in the present study elicited a "slow component-like" increase in intramuscular ATP OX gain as well as a progressive increase in the phosphate cost of contraction. Furthermore, the development of peripheral fatigue was closely related to the perturbation of specific fatigue-inducing intramuscular factors (i.e., pH and [Formula: see text] concentration). NEW & NOTEWORTHY The physiological mechanisms and skeletal muscle bioenergetics underlying all-out exercise performance are unclear. This study revealed an increase in oxidative ATP synthesis rate gain and the ATP cost of contraction during all-out exercise. Furthermore, peripheral fatigue was related to the perturbation in pH and deprotonated phosphate ion. These findings support the concept that the oxygen uptake slow component arises from within active skeletal muscle and that skeletal muscle force generating capacity is linked to the intramuscular metabolic milieu.

Key Points: The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise-induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural 'drive' to working locomotor muscle and limits the exercise-induced intramuscular metabolic perturbation. Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance., Abstract: To investigate the role of metabo- and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise-induced changes in intramuscular metabolites were determined using liquid and gas chromatography-mass spectrometry. Quadriceps fatigue was quantified by pre- to post-exercise changes in potentiated quadriceps twitch torque (ΔQTsingle ) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial was similar (∼8.8 min). Compared to CTRL, power output during FENT was 10 ± 4% higher in the first half of the time trial, but 11 ± 5% lower in the second half (both P < 0.01). The exercise-induced increase in intramuscular inorganic phosphate, H(+) , adenosine diphosphate, lactate and phosphocreatine depletion was 55 ± 30, 62 ± 18, 129 ± 63, 47 ± 14 (P < 0.001) and 27 ± 14% (P < 0.01) greater in FENT than CTRL. ΔQTsingle was greater following FENT than CTRL (-52 ± 2 vs -31 ± 1%, P < 0.001) and this difference was positively correlated with the difference in inorganic phosphate (r(2)  = 0.79; P < 0.01) and H(+) (r(2)  = 0.92; P < 0.01). In conclusion, during whole body exercise, group III/IV muscle afferents provide feedback to the CNS which, in turn, constrains motoneuronal output to the active skeletal muscle. This regulatory mechanism limits the exercise-induced intramuscular metabolic perturbation, preventing an abnormal homeostatic challenge and excessive peripheral fatigue., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Purpose: We investigated the development and recovery of peripheral and central fatigue during repeated cycling sprints and its influence on power output., Methods: On six separate days, 12 healthy males performed the following tests: 1, 4, 6, 8, and 10 × 10 s sprints with 30 s of passive recovery between sprints, as well as 8 × 10 s sprints with 10 s of passive recovery. Peripheral and central fatigue levels were quantified via changes in preexercise- to postexercise-potentiated quadriceps twitch force, as evoked by supramaximal electrical stimulation of the femoral nerve (30 s through 6 min recovery), and quadriceps voluntary activation (VA), respectively. Root mean square of the vastus lateralis and the vastus medialis electromyogram during sprints were normalized by maximal M wave amplitude (RMS·Mmax)., Results: From the first to the sixth sprint, we found significant and gradual reductions in power output (-25% ± 7%), RMS·Mmax (-7% ± 4%), twitch force (-47% ± 11%) and VA (-11% ± 6%). During the subsequent sprints, no additional reduction in power output, RMS·Mmax, twitch force or VA, was found. Reduction in between-sprints recovery duration led to a significant reduction in power output and RMS·Mmax but no change in peripheral and central fatigue., Conclusion: These findings are consistent with the hypothesis that central motor command and power output during all-out repeated sprints are limited in order to prevent excessive locomotor muscle fatigue. They also demonstrate that both the peripheral and central fatigue contribute significantly to the decline in power output elicited via repeated sprints.

We hypothesized that exercise performance is adjusted during repeated sprints in order not to surpass a critical threshold of peripheral fatigue. Twelve men randomly performed three experimental sessions on different days, i.e. one single 10 s all-out sprint and two trials of 10 × 10 s all-out sprints with 30 s of passive recovery in between. One trial was performed in the unfatigued state (CTRL) and one following electrically induced quadriceps muscle fatigue (FTNMES). Peripheral fatigue was quantified by comparing pre- with postexercise changes in potentiated quadriceps twitch force (ΔQtw-pot) evoked by supramaximal magnetic stimulation of the femoral nerve. Central fatigue was estimated by comparing pre- with postexercise voluntary activation of quadriceps motor units. The root mean square (RMS) of the vastus lateralis and vastus medialis EMG normalized to maximal M-wave amplitude (RMS.Mmax (-1)) was also calculated during sprints. Compared with CTRL condition, pre-existing quadriceps muscle fatigue in FTNMES (ΔQtw-pot = -29 ± 4%) resulted in a significant (P < 0.05) reduction in power output (-4.0 ± 0.9%) associated with a reduction in RMS.Mmax (-1). However, ΔQtw-pot postsprints decreased by 51% in both conditions, indicating that the level of peripheral fatigue was identical and independent of the degree of pre-existing fatigue. Our findings show that power output and cycling EMG are adjusted during exercise in order to limit the development of peripheral fatigue beyond a constant threshold. We hypothesize that the contribution of peripheral fatigue to exercise limitation involves a reduction in central motor drive in addition to the impairment in muscular function., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)