Muscle Afferent Feedback Research Articles

Control of hyperpnoea and pulmonary gas exchange during prolonged exercise: The role of group III/IV muscle afferent feedback.

It remains unclear whether feedback from group III/IV muscle afferents is of continuous significance for regulating the pulmonary response during prolonged (>5min), steady-state exercise. To elucidate the influence of these sensory neurons on hyperpnoea, gas exchange efficiency, arterial oxygenation and acid-base balance during prolonged locomotor exercise, 13healthy participants (4 females; 21 (3) years, : 46 (8) ml/kg/min) performed consecutive constant-load cycling bouts at ∼50% (20min), ∼75% (20min) and ∼100% (5min) of with intact (CTRL) and pharmacologically attenuated (lumbar intrathecal fentanyl; FENT) group III/IV muscle afferent feedback from the legs. Pulmonary responses were continuously recorded and arterial blood (radial catheter) periodically collected throughout the exercise. Pulmonary gas exchange efficiency was evaluated using the alveolar-arterial difference ( ). There were no differences in any of the variables of interest between conditions before the start of the exercise. Pulmonary ventilation was up to 20% lower across all intensities during FENT compared to CTRL exercise (P<0.001) and this hypoventilation was accompanied by an up to 10% lower arterial and a 2-4mmHg higher (both P<0.001). The exercise-induced widening of was up to 25% larger during FENT compared to CTRL (P<0.001). Importantly, the differences developed within the first minute of each stage and persisted, or further increased, throughout the remainder of each bout. These findings reflect a critical and time-independent significance of feedback from group III/IV leg muscle afferents for continuously regulating the ventilatory response, gas exchange efficiency, arterial oxygenation and acid-base balance during human locomotion. KEY POINTS: Feedback from group III/IV leg muscle afferents reflexly contributes to hyperpnoea during short duration (i.e. <5min) locomotor exercise. Whether continuous feedback from these sensory neurons is obligatory to ensure adequate pulmonary responses during steady-state exercise of longer duration remains unknown. Lumbar intrathecal fentanyl was used to attenuate the central projection of group III/IV leg muscle afferents during prolonged locomotor exercise (i.e. 45min) at intensities ranging from 50% to 100% of . Without affecting the metabolic rate, afferent blockade compromised pulmonary ventilation and gas exchange efficiency, consistently impairing arterial oxygenation and facilitating respiratory acidosis throughout exercise. These findings reflect the time-independent significance of feedback from group III/IV muscle afferents for regulating exercise hyperpnoea and gas exchange efficiency, and thus for optimizing arterial oxygenation and acid-base balance, during prolonged human locomotion.

The effects of plantarflexor weakness and reduced tendon stiffness with aging on gait stability.

Falls among older adults are a costly public health concern. Such falls can be precipitated by balance disturbances, after which a recovery strategy requiring rapid, high force outputs is necessary. Sarcopenia among older adults likely diminishes their ability to produce the forces necessary to arrest gait instability. Age-related changes to tendon stiffness may also delay muscle stretch and afferent feedback and decrease force transmission, worsening fall outcomes. However, the association between muscle strength, tendon stiffness, and gait instability is not well established. Given the ankle's proximity to the onset of many walking balance disturbances, we examined the relation between both plantarflexor strength and Achilles tendon stiffness with walking-related instability during perturbed gait in older and younger adults-the latter quantified herein using margins of stability and whole-body angular momentum including the application of treadmill-induced slip perturbations. Older and younger adults did not differ in plantarflexor strength, but Achilles tendon stiffness was lower in older adults. Among older adults, plantarflexor weakness associated with greater whole-body angular momentum following treadmill-induced slip perturbations. Weaker older adults also appeared to walk and recover from treadmill-induced slip perturbations with more caution. This study highlights the role of plantarflexor strength and Achilles tendon stiffness in regulating lateral gait stability in older adults, which may be targets for training protocols seeking to minimize fall risk and injury severity.

Consequences of group III/IV afferent feedback and respiratory muscle work on exercise tolerance in heart failure with reduced ejection fraction.

Exercise intolerance and exertional dyspnoea are the cardinal symptoms of heart failure with reduced ejection fraction (HFrEF). In HFrEF, abnormal autonomic and cardiopulmonary responses arising from locomotor muscle group III/IV afferent feedback is one of the primary mechanisms contributing to exercise intolerance. HFrEF patients also have pulmonary system and respiratory muscle abnormalities that impair exercise tolerance. Thus, the primary impetus for this review was to describe the mechanistic consequences of locomotor muscle group III/IV afferent feedback and respiratory muscle work in HFrEF. To address this, we first discuss the abnormal autonomic and cardiopulmonary responses mediated by locomotor muscle afferent feedback in HFrEF. Next, we outline how respiratory muscle work impairs exercise tolerance in HFrEF through its effects on locomotor muscle O2 delivery. We then discuss the direct and indirect evidence supporting an interaction between locomotor muscle group III/IV afferent feedback and respiratory muscle work during exercise in HFrEF. Last, we outline future research directions related to locomotor and respiratory muscle abnormalities to progress the field forward in understanding the pathophysiology of exercise intolerance in HFrEF. NEW FINDINGS: What is the topic of this review? This review is focused on understanding the role that locomotor muscle group III/IV afferent feedback and respiratory muscle work play in the pathophysiology of exercise intolerance in patients with heart failure. What advances does it highlight? This review proposes that the concomitant effects of locomotor muscle afferent feedback and respiratory muscle work worsen exercise tolerance and exacerbate exertional dyspnoea in patients with heart failure.

The exercise pressor reflex - a pressure-raising mechanism with a limited role in regulating leg perfusion during locomotion in young healthy men.

We investigated the role of the exercise pressor reflex (EPR) in regulating the haemodynamic response to locomotor exercise. Eight healthy participants (23±3years, : 49±6ml/kg/min) performed constant-load cycling exercise (∼36/43/52/98% ; 4min each) without (CTRL) and with (FENT) lumbar intrathecal fentanyl attenuating group III/IV locomotor muscle afferent feedback and, thus, the EPR. To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during FENT, subjects mimicked the ventilatory response recorded during CTRL. Arterial and leg perfusion pressure (femoral arterial and venous catheters), femoral blood flow (Doppler-ultrasound), microvascular quadriceps blood flow index (indocyanine green), cardiac output (inert gas breathing), and systemic and leg vascular conductance were quantified during exercise. There were no cardiovascular and ventilatory differences between conditions at rest. Pulmonary ventilation, arterial blood gases and oxyhaemoglobin saturation were not different during exercise. Furthermore, cardiac output (-2% to -12%), arterial pressure (-7% to -15%) and leg perfusion pressure (-8% to -22%) were lower, and systemic (up to 16%) and leg (up to 27%) vascular conductance were higher during FENT compared to CTRL. Leg blood flow, microvascular quadriceps blood flow index, and leg O2 -transport and utilization were not different between conditions (P>0.5). These findings reflect a critical role of the EPR in the autonomic control of the heart, vasculature and, ultimately, arterial pressure during locomotor exercise. However, the lack of a net effect of the EPR on leg blood flow challenges the idea of this cardiovascular reflex as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals. KEY POINTS: The role of the exercise pressor reflex (EPR) in regulating leg O2 -transport during human locomotion remains uncertain. We investigated the influence of the EPR on the cardiovascular response to cycling exercise. Lumbar intrathecal fentanyl was used to block group III/IV leg muscle afferents and debilitate the EPR at intensities ranging from 30% to 100% . To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during exercise with blocked leg muscle afferents, subjects mimicked the ventilatory response recorded during control exercise. Afferent blockade increased leg and systemic vascular conductance, but reduced cardiac output and arterial-pressure, with no net effect on leg blood flow. The EPR influenced the cardiovascular response to cycling exercise by contributing to the autonomic control of the heart and vasculature, but did not affect leg blood flow. These findings challenge the idea of the EPR as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals.

The central motor command, but not the muscle afferent feedback, is necessary to perceive effort

The central motor command, but not the muscle afferent feedback, is necessary to perceive effort

On the significance of group III/IV muscle afferent feedback for the control of breathing and gas exchange efficiency during prolonged locomotor exercise

Introduction: By projecting to medullary respiratory center, group III/IV muscle afferents determine the ventilatory response during short (~3 min) bouts of locomotor exercise. However, their significance for the hyperpneic response, gas exchange efficiency, and arterial oxygenation during exercise of longer durations (&gt;15min) remains unknown. Methods: On 2 separate days, 8 healthy subjects (22±3yrs, 4 f) performed two 20-min bicycling bouts at 30% (~50% V̇O2max) and 50% (~75% V̇O2max) of peak power (Wpeak) under a) control condition (intact leg muscle afferent feedback; CTRL), and b) lumbar intrathecal fentanyl (attenuated group III/IV leg muscle afferent feedback; FENT). Ventilation (V̇E) and gas exchange were continuously recorded, data averaged over the last min of each bout. Arterial blood samples (radial catheter) were used to determine O2 and CO2 partial pressures (PaO2 and PaCO2) and O2 saturation (HbO2). Alveolar O2 pressure (PAO2) was calculated, pulmonary gas exchange efficiency was evaluated using the alveolar-to-arterial O2 difference (A-aDO2) and the arterial-to-end-tidal PCO2 difference (PaCO2-PETCO2). Results: Fentanyl had no effect at rest. There was no difference in V̇O2, V̇CO2, and VT between CTRL and FENT. However, during FENT vs CTRL, V̇E (30 % Wpeak: 42±9 vs 46±8 L/min; 50 %Wpeak: 75±12 vs 71±12), f R (30 %: 25±3 vs 28±4b/min; 50%: 33±5 vs 35±5), V̇E/V̇O2 (30%: 25±3 vs 28±3; 50 %: 29±5 vs 32±4), V̇E/V̇CO2 (30 %: 31±4 vs 34±4; 50 %: 34±5 vs 37±5), PAO2 (30 %: 94±3 vs 97±5 mmHg; 50 %: 98±3 vs 100±4), PaO2 (30%: 84±5 vs 90±3 mmHg; 50%: 84±7 vs 88±4), HbO2 (30 %: 95±1 vs 96±1 %; 50 %: 95±2 vs 96±1 %), VD/VT (30 %: 0.18±0.04 vs 0.22±0.08; 50 %: 0.16±0.05 vs 0.21±0.07), and the PaCO2-PETCO2 difference (30 %: -2.6±1.6 vs -1.4±2.1 mmHg; 50 %: -2.8±2.4 vs -1.0±2.1) were lower ( P&lt;0.05), while PaCO2 (30 %: 33±3 vs 31±3 mmHg; 50 %: 30±3 vs 29±3) and A-aDO2 (30 %: 9±3 vs 5±5 mmHg; 50 %: 14±5 vs 10±5) were greater ( P&lt;0.05). Conclusions: In addition to regulating the initial ventilatory response, tonic feedback from group III/IV muscle afferents remains a key determinant of the pulmonary response during prolonged locomotor exercise. The relative importance of these sensory neurons for optimizing exercise hyperpnea is emphasized by the fact that the pulmonary response to bicycling with attenuated sensory feedback remains inadequate despite concomitant increases in potent ventilatory stimuli (↑PaCO2, ↓PaO2). We conclude that group III/IV muscle afferent feedback is critical for matching the pulmonary response to the metabolic cost of locomotion and for perpetually optimizing gas exchange efficiency and arterial oxygenation during longer exercise. National Heart, Lung, and Blood Institute (HL-116579), U.S. Veterans Affairs Rehabilitation Research and Development (E3343-R) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential control of respiratory frequency and tidal volume during exercise.

The lack of a testable model explaining how ventilation is regulated in different exercise conditions has been repeatedly acknowledged in the field of exercise physiology. Yet, this issue contrasts with the abundance of insightful findings produced over the last century and calls for the adoption of new integrative perspectives. In this review, we provide a methodological approach supporting the importance of producing a set of evidence by evaluating different studies together-especially those conducted in 'real' exercise conditions-instead of single studies separately. We show how the collective assessment of findings from three domains and three levels of observation support the development of a simple model of ventilatory control which proves to be effective in different exercise protocols, populations and experimental interventions. The main feature of the model is the differential control of respiratory frequency (fR) and tidal volume (VT); fR is primarily modulated by central command (especially during high-intensity exercise) and muscle afferent feedback (especially during moderate exercise) whereas VT by metabolic inputs. Furthermore, VT appears to be fine-tuned based on fR levels to match alveolar ventilation with metabolic requirements in different intensity domains, and even at a breath-by-breath level. This model reconciles the classical neuro-humoral theory with apparently contrasting findings by leveraging on the emerging control properties of the behavioural (i.e. fR) and metabolic (i.e. VT) components of minute ventilation. The integrative approach presented is expected to help in the design and interpretation of future studies on the control of fR and VT during exercise.

Pharmacological Blockade of Muscle Afferents and Perception of Effort: A Systematic Review with Meta-analysis.

The perception of effort provides information on task difficulty and influences physical exercise regulation and human behavior. This perception differs from other-exercise related perceptions such as pain. There is no consensus on the role of group III/IV muscle afferents as a signal processed by the brain to generate theperception of effort. The aim of this meta-analysis was to investigate the effect of pharmacologically blocking muscle afferents on the perception of effort. Six databases were searched to identify studies measuring the ratings of perceived effort during physical exercise, with and without pharmacological blockade of muscle afferents. Articles were coded based on the operational measurement used to distinguish studies in which perception of effort was assessed specifically (effort dissociated) or as a composite experience including other exercise-related perceptions (effort not dissociated). Articles that did not provide enough information for coding were assigned to the unclear group. The effort dissociated group (n = 6) demonstrated a slightincrease in ratings of perceived effort with reduced muscle afferent feedback (standard mean change raw, 0.39; 95% confidence interval 0.13-0.64). The group effort not dissociated (n = 2) did not reveal conclusive results (standard mean change raw, - 0.29; 95% confidence interval - 2.39 to 1.8). The group unclear (n = 8) revealed a slight ratings of perceived effort decrease with reduced muscle afferent feedback (standard mean change raw, - 0.27; 95% confidence interval - 0.50 to - 0.04). The heterogeneity in results between groups reveals that the inclusion of perceptions other than effort in its rating influences the ratings of perceived effort reported by the participants. The absence of decreased ratings of perceived effort in the effort dissociated group suggests that muscle afferent feedback is not a sensory signal for theperception of effort.

Locomotor Muscle Afferent Inhibition Augments Activation Of Locomotor Muscles In Heart Failure Patients During Exercise

Exercise intolerance is a hallmark feature of heart failure with reduced ejection fraction (HFrEF). Locomotor muscle afferent feedback contributes to exercise intolerance in patients with HFrEF. Locomotor muscle afferent inhibition via intrathecal fentanyl, compared to the sham condition (SHAM), results in increased peak workload, cardiac output, and leg oxygen delivery during maximal exercise. To date, the impact of locomotor muscle afferent feedback inhibition on locomotor muscle activation responses during exercise in patients with HFrEF have not been investigated. PURPOSE: To determine the effect of intrathecal fentanyl on vastus lateralis (VL) muscle activation during incremental exercise in patients with HFrEF. METHODS: Patients with HFrEF (n = 7, EF: 35 ± 13%, age: 60 ± 9 yrs, BMI 28.7 ± 5.5 kg/m2) performed an incremental cycle test to task failure with lumbar intrathecal fentanyl (FENT) or SHAM (in randomized order). Electromyography (EMG) of the VL was measured and the root-mean square (RMS) of 10 contractions were averaged at 30 W, 50 W, 70 W, and peak workload. Changes in RMS were normalized as a percent of the SHAM response (unloaded = 0%; peak workload = 100%). RESULTS: Peak workload was significantly greater with FENT compared to SHAM (129 ± 30 vs. 114 ± 31 W, p = 0.04). VL RMS was not different at 30 W between FENT and SHAM (FENT: 44 ± 22 vs. SHAM: 17 ± 33%, p = 0.06). However, VL RMS was greater with FENT compared to SHAM at 50 W (FENT: 82 ± 61 vs. SHAM: 31 ± 24%), 70 W (FENT: 96 ± 56 vs. SHAM: 45 ± 29%), and peak workload (FENT: 167 ± 55 vs. SHAM: 92 ± 10%) (all, p < 0.04). There was no significant relationship between the change in peak workload and VL RMS with FENT with both normalized as a percent of the SHAM response (p = 0.09). CONCLUSION: These data suggest that locomotor muscle afferent feedback may contribute to exercise intolerance via inhibition of locomotor muscle activation during exercise in patients with HFrEF.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Crosstalk opposing view: Independent fusimotor control of muscle spindles in humans: there is little to gain.

Crosstalk opposing view: Independent fusimotor control of muscle spindles in humans: there is little to gain.

Electrically induced quadriceps fatigue in the contralateral leg impairs ipsilateral knee extensors performance.

Muscle fatigue induced by voluntary exercise, which requires central motor drive, causes central fatigue that impairs endurance performance of a different, nonfatigued muscle. This study investigated the impact of quadriceps fatigue induced by electrically induced (no central motor drive) contractions on single-leg knee-extension (KE) performance of the subsequently exercising ipsilateral quadriceps. On two separate occasions, eight males completed constant-load (85% of maximal power-output) KE exercise to exhaustion. In a counterbalanced manner, subjects performed the KE exercise with no pre-existing quadriceps fatigue in the contralateral leg on one day (No-PreF), whereas on the other day, the same KE exercise was repeated following electrically induced quadriceps fatigue in the contralateral leg (PreF). Quadriceps fatigue was assessed by evaluating pre- to postexercise changes in potentiated twitch force (ΔQtw,pot; peripheral fatigue), and voluntary muscle activation (ΔVA; central fatigue). As reflected by the 57 ± 11% reduction in electrically evoked pulse force, the electrically induced fatigue protocol caused significant knee-extensors fatigue. KE endurance time to exhaustion was shorter during PreF compared with No-PreF (4.6 ± 1.2 vs 7.7 ± 2.4 min; P < 0.01). Although ΔQtw,pot was significantly larger in No-PreF compared with PreF (-60% vs -52%, P < 0.05), ΔVA was greater in PreF (-14% vs -10%, P < 0.05). Taken together, electrically induced quadriceps fatigue in the contralateral leg limits KE endurance performance and the development of peripheral fatigue in the ipsilateral leg. These findings support the hypothesis that the crossover effect of central fatigue is mainly mediated by group III/IV muscle afferent feedback and suggest that impairments associated with central motor drive may only play a minor role in this phenomenon.

Contrasting effects of heat stress on neuromuscular performance.

What is the central question of this review? Is exposure to a hot environment detrimental to neuromuscular performance? What is the main finding and what is its importance? Elevating body temperature improves peak power during short-duration, high-intensity exercise but trades off with an accelerated rate of decay. Higher muscle temperatures and cross-bridge cycling rate resemble a shift in contractile characteristic to a faster phenotype. Prolonged moderate-intensity exercise capacity is impaired in a hot environment. Fatigue appears to combine a reduced drive from the CNS and increased cardiovascular strain to maintain skeletal muscle perfusion and thermoregulation. The effect of thermal stress on human work capacity and neuromuscular function has been of interest to physiologists since the 19th century. The aim of the present review is to examine the impact of exposure to heat stress on neuromuscular performance. Exposure to heat stress during exercise is known to increase strain on the cardiovascular system owing to the competing demands of skeletal muscle perfusion and homeostatic thermoregulation. The effects of exposure to heat stress on the neuromuscular system are more complex, because in some circumstances an elevation in muscle temperature leads to an improvement in function, whereas in other circumstances an increase in temperature leads to a decrement in function that is a consequence of the mode, metabolic demand and duration of the exercise. The ability to sustain isometric tension is impaired with an elevated muscle temperature and so too is locomotor capacity over prolonged periods of time. In contrast, peak power production is enhanced by increasing muscle temperature but is achieved at the expense of maintaining power output, owing to a higher rate of decay in power production. The different effects on neuromuscular function at an elevated muscle temperature are explained, in part, by a higher rate of energy turnover. In addition, the effect of an elevated core temperature also appears to impair neuromuscular performance either owing to a reduced voluntary drive in motor unit recruitment or to a failure in muscle afferent feedback, or a combination of the two.

Electrical Stimulation-induced Fatigue In The Contralateral Leg Impairs Endurance Exercise Performance

During fatiguing exercise, the development of peripheral fatigue and the associated increased firing of group III/IV afferent fibres, promote central fatigue. PURPOSE: The aim of this study was to assess whether peripheral fatigue in the contralateral leg induced by electrical quadriceps stimulation to bypass central command, would impair endurance performance of the subsequently exercising ipsilateral leg. METHODS: Eight young healthy males were recruited for this study. After completing an incremental test to exhaustion on a single-leg knee extensor ergometer, the subjects performed two tests on separate days. On the first day, they performed a time-to-exhaustion test at 85% of their maximal power output (No-PreF trial). Exercise-induced quadriceps muscle fatigue was assessed by supramaximal electrical femoral nerve stimulation evaluating changes in the potentiated resting twitch force (Qtw,pot), maximal voluntary contraction (MVC) and voluntary activation (VA) from pre to post exercise. On the second day, the same exercise bout was preceded by the induction of fatigue in the contralateral quadriceps through electrical stimulation (PreF trial). The pre-fatiguing protocol was terminated once the subjects reached the maximum tolerance score on a 1-10 visual analogue scale (duration: 6.6 ± 0.9 min). Integrated electromyography (iEMG) was recorded and used to estimate spinal motoneuronal output. RESULTS: Time to exhaustion in the PreF trial was reduced by 41% (9.1 ± 1.5 to 5.4 ± 1.2 min, p < 0.05). The reduction in MVC (-36 ± 8 vs -23 ± 10%, p < 0.05) and Qtw,pot (-53 ± 3 to -39 ± 9% p < 0.05) was more accentuated in the No-PreF trial compared to PreF. Conversely, VA was more affected in PreF than in No-PreF (-20 ± 7 vs -14 ± 5%, p < 0.05). At every submaximal time point, iEMG was significantly higher in PreF compared to No-PreF, while at exhaustion it was higher in the latter (p<0.05). CONCLUSIONS: Pre-induced muscle fatigue in the contralateral limb impairs endurance performance of the exercising ipsilateral limb. This cross-over effect of fatigue is likely mediated by the inhibitory influence associated with group III/IV muscle afferent feedback and not related to changes associated with central command.Funding: No funding was received for this study

The carotid bodies exercise control over active expiration but not peak performance during high-intensity treadmill running.

The carotid bodies exercise control over active expiration but not peak performance during high-intensity treadmill running.

Combined influence of inspiratory loading and locomotor subsystolic cuff inflation on cardiovascular responses during submaximal exercise.

It is unknown if simultaneous stimulation of the respiratory and locomotor muscle afferents via inspiratory loading (IL) and locomotor subsystolic cuff inflation (CUFF) influences the cardiovascular responses during exercise. We hypothesized that combined IL and CUFF (IL + CUFF) will result in greater increases in blood pressure (MAP) and systemic vascular resistance (SVR) than IL and CUFF alone during exercise. Eight adults (6 males/2 females) were enrolled and performed four 10-min bouts of constant-load cycling eliciting 40% maximal oxygen uptake on a single day. For each exercise bout, the first 5 min consisted of spontaneous breathing. The second 5 min consisted of voluntary hyperventilation (i.e., breathing frequency of 40 breaths/min) with IL (30% maximum inspiratory pressure), CUFF (80 mmHg), IL + CUFF, or no intervention (CTL) in randomized order. During exercise, cardiac output and MAP were determined via open-circuit acetylene wash-in and manual sphygmomanometry, respectively, and SVR was calculated. Across CTL, IL, CUFF, and IL + CUFF, MAP was greater with each condition (CTL: 97 ± 14; IL: 106 ± 13; CUFF: 114 ± 14; IL + CUFF: 119 ± 15 mmHg, all P < 0.02). Furthermore, SVR was greater with IL + CUFF compared with IL, CUFF, and CTL (CTL: 6.6 ± 1.1; IL: 7.5 ± 1.4; CUFF: 7.5 ± 1.3; IL + CUFF: 8.2 ± 1.4 mmHg·L-1·min-1, all P < 0.02). Cardiac output was not different across conditions (CTL: 15.2 ± 3.8; IL: 14.8 ± 3.7; CUFF: 15.6 ± 3.5; IL + CUFF: 14.7 ± 4.3 L/min, all P > 0.05). These data demonstrate that simultaneous stimulation of respiratory and locomotor muscle afferent feedback results in additive MAP and SVR responses than IL and CUFF alone during submaximal exercise. These findings have important clinical implications for populations with exaggerated locomotor and respiratory muscle reflex feedbacks.NEW & NOTEWORTHY Reflexes arising from the respiratory and locomotor muscles influence cardiovascular regulation during exercise. However, it is unclear how the respiratory and locomotor muscle reflexes interact when simultaneously stimulated. Herein, we demonstrate that stimulation of the respiratory and locomotor muscle reflexes yielded additive cardiovascular responses during submaximal exercise.

Metabo- and mechanoreceptor expression in human heart failure: Relationships with the locomotor muscle afferent influence on exercise responses.

What is the central question of this study? How do locomotor muscle metabo- and mechanoreceptor expression compare in heart failure patients and controls? Do relationships exist between the protein expression and cardiopulmonary responses during exercise with locomotor muscle neural afferent feedback inhibition? What is the main finding and its importance? Heart failure patients exhibited greater protein expression of transient receptor potential vanilloid type 1 and cyclooxygenase-2 than controls. These findings are important as they identify receptors that may underlie the augmented locomotor muscle neural afferent feedback in heart failure. Heart failure patients with reduced ejection fraction (HFrEF) exhibit abnormal locomotor group III/IV afferent feedback during exercise; however, the underlying mechanisms are unclear. Therefore, the purpose of this study was to determine (1) metabo- and mechanoreceptor expression in HFrEF and controls and (2) relationships between receptor expression and changes in cardiopulmonary responses with afferent inhibition. Ten controls and six HFrEF performed 5min of cycling exercise at 65% peak workload with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Arterial blood pressure and catecholamines were measured via radial artery catheter. A vastus lateralis muscle biopsy was performed to quantify cyclooxygenase-2 (COX-2), purinergic 2X3 (P2X3 ), transient receptor potential vanilloid type 1 (TRPV 1), acid-sensing ion channel 3 (ASIC3 ), Piezo 1 and Piezo 2 protein expression. TRPV 1 and COX-2 protein expression was greater in HFrEF than controls (both P<0.04), while P2X3 , ASIC3 , and Piezo 1 and 2 were not different between groups (all P>0.16). In all participants, COX-2 protein expression was related to the percentage change in ventilation (r=-0.66) and mean arterial pressure (MAP) (r=-0.82) (both P<0.01) with FENT (relative to PLA) during exercise. In controls, TRPV 1 protein expression was related to the percentage change in systolic blood pressure (r=-0.77, P=0.02) and MAP (r=-0.72, P=0.03) with FENT (relative to PLA) during exercise. TRPV 1 and COX-2 protein levels are elevated in HFrEF compared to controls. These findings suggest that the elevated TRPV 1 and COX-2 expression may contribute to the exaggerated locomotor muscle afferent feedback during cycling exercise in HFrEF.

The Sexes Do Not Differ for Neural Responses to Submaximal Elbow Extensor Fatigue.

To investigate possible sex-related differences in group III/IV muscle afferent feedback with isometric fatigue, we aimed to assess the effect of a sustained submaximal elbow extensor contraction on motoneuronal excitability (cervicomedullary motor evoked potential [CMEP]) and voluntary activation (VA). Twenty-four participants (12 females) performed a 15-min contraction at the level of EMG activity recorded at 15% of maximal torque. Each minute, CMEP were elicited by cervicomedullary stimulation with and without conditioning transcranial magnetic stimulation (TMS) delivered 100 ms earlier. Unconditioned and conditioned motor evoked potentials (MEP) in response to TMS were also recorded to assess motor cortical excitability. CMEP and MEP were normalized for changes in downstream excitability and expressed as percentage of their prefatigue (control) values. Postfatigue, VA was calculated from superimposed and resting tetani evoked by stimulation over triceps brachii. Males were twice as strong as females, but the sexes did not differ for any variable during the fatigue protocol. On a 0-10 scale, RPE increased from ~2.5 to 9. The unconditioned CMEP did not change, whereas the conditioned CMEP was reduced by ~50%. By contrast, the unconditioned and conditioned MEP increased to ~200% and ~320% of the control values, respectively. At task termination, maximal torque was reduced ~40%, and VA was ~80%, down from a prefatigue value of ~96%. Results support the scant published data on the elbow extensors and indicate no sex-related differences for isometric fatigue of this muscle group. The motoneuronal and VA data suggest that metabolite buildup and group III/IV muscle afferent activity were similar for females and males.

Effect of blood flow occlusion on corticospinal excitability during sustained low-intensity isometric elbow flexion.

Blood flow occlusion (BFO) has been used to study the influence of group III/IV muscle afferents after fatiguing exercise, but it is unknown how BFO-induced activity of these afferents affects motor cortical and motoneuronal excitability during low-intensity exercise. Therefore, the purpose of this study was to assess the acute effect of BFO on peripheral [maximal M wave (Mmax)], spinal [cervicomedullary motor evoked potential (CMEP) normalized to Mmax], and motor cortical [motor evoked potential (MEP) normalized to CMEP] excitability. Nine healthy men completed a sustained isometric contraction of the elbow flexors at 20% of maximal force under three conditions: 1) contractile failure with BFO, 2) a time-matched trial without restriction [free flow (FFiso)], and 3) contractile failure with free flow (FFfail). Time to failure for BFO (and FFiso) were ~80% shorter than that for FFfail (P < 0.05). For FFfail and FFiso, Mmax area decreased ~17% and ~7%, respectively (P < 0.05), with no change during BFO. CMEP/Mmax area increased ~226% and ~80% during BFO and FFfail, respectively (P < 0.05), with no change during FFiso (P > 0.05). The increase in normalized CMEP area was greater for BFO and FFfail compared with FFiso and for BFO compared with FFfail. MEP/CMEP area was not different among the protocols (P > 0.05) and increased ~64% with time (P < 0.05). It is likely that group III/IV muscle afferent feedback to the spinal cord modulates the large increase in motoneuronal excitability for the BFO compared with FFfail and FFiso protocols.NEW & NOTEWORTHY We have observed how blood flow occlusion modulates motor cortical, spinal, and peripheral excitability during and immediately after a sustained low-intensity isometric elbow flexion contraction to failure. We conclude that blood flow occlusion causes a greater and more rapid increase in motoneuronal excitability.

Control of exercise hyperpnoea: Contributions from thin-fibre skeletal muscle afferents.

What is the topic of this review? In this review, we examine the evidence for control mechanisms underlying exercise hyperpnoea, giving attention to the feedback from thin-fibre skeletal muscle afferents, and highlight the frequently conflicting findings and difficulties encountered by researchers using a variety of experimental models. What advances does it highlight? There has been a recent resurgence of interest in the role of skeletal muscle afferent involvement, not only as a mechanism of healthy exercise hyperpnoea but also in the manifestation of breathlessness and exercise intolerance in chronic disease. The ventilatory response to dynamic submaximal exercise is immediate and proportional to metabolic rate, which maintains isocapnia. How these respiratory responses are controlled remains poorly understood, given that the most tightly controlled variable (arterial partial pressure of CO2 /H+ ) provides no error signal for arterial chemoreceptors to trigger reflex increases in ventilation. This review discusses evidence for different postulated control mechanisms, with a focus on the feedback from groupIII/IV skeletal muscle mechanosensitive and metabosensitive afferents. This concept is attractive, because the stimulation of muscle mechanoreceptors might account for the immediate increase in ventilation at the onset of exercise, and signals from metaboreceptors might be proportional to metabolic rate. A variety of experimental models have been used to establish the contribution of thin-fibre muscle afferents in ventilatory control during exercise, with equivocal results. The inhibition of afferent feedback via the application of lumbar intrathecal fentanyl during exercise suppresses ventilation, which provides the most compelling supportive evidence to date. However, stimulation of afferent feedback at rest has no consistent effect on respiratory output. However, evidence is emerging for synergistic interactions between muscle afferent feedback and other stimulatory inputs to the central respiratory neuronal pool. These seemingly hyperadditive effects might explain the conflicting findings encountered when using different experimental models. We also discuss the increasing evidence that patients with certain chronic diseases exhibit exaggerated muscle afferent activation during exercise, resulting in enhanced cardiorespiratory responses. This might provide a neural link between the well-established limb muscle dysfunction and the associated exercise intolerance and exertional dyspnoea, which might offer therapeutic targets for these patients.