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 (>5 min), 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, 13 healthy participants (4 females; 21 (3) years, V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ : 46 (8) ml/kg/min) performed consecutive constant-load cycling bouts at ∼50% (20 min), ∼75% (20 min) and ∼100% (5 min) of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ 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 P O 2 ${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ difference ( A - a D O 2 ${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ). 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 P O 2 ${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and a 2-4 mmHg higher P C O 2 ${{P}_{{\mathrm{C}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ (both P < 0.001). The exercise-induced widening of A - a D O 2 ${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ 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. <5 min) 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. 45 min) at intensities ranging from 50% to 100% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ . 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.

Hypertension restricts leg blood flow and aggravates neuromuscular fatigue during human locomotion in males.

Patients with hypertension (HTN) are characterized by exaggerated vascular resistance and mean arterial pressure (MAP) and a compromised leg blood flow (QL) response to exercise recruiting a small muscle mass. However, the impact of hypertension on peripheral hemodynamics and the development of neuromuscular fatigue during locomotor activities, which critically depends on QL, remain unknown. Eight HTN (143 ± 11 mmHg/95 ± 6 mmHg; 45 ± 13 yr) and eight matched (age and activity) controls (120 ± 6 mmHg/77 ± 7 mmHg; CTRL) performed constant-load cycling exercise at 25, 50, and 75 W (for 4 min each) and at 165 ± 41 W (for 5 min). Exercise-induced locomotor muscle fatigue was quantified as the pre- to postexercise change in quadriceps twitch-torque (ΔQtw, peripheral fatigue) and voluntary activation (ΔVA%, central fatigue). QL (Doppler ultrasound) and leg vascular conductance (LVC) were determined during cycling at 25, 50, and 75 W. Heart rate and ventilatory responses were recorded during all intensities. MAP during exercise was, on average, ∼21 mmHg higher (P = 0.002) and LVC ∼39% lower (P = 0.001) in HTN compared with CTRL. QL was consistently between 20 and 30% lower (P = 0.004), and heart rate was significantly higher in HTN. Exercise-induced peripheral (ΔQtw: -53 ± 19% vs. -25 ± 23%) and central (ΔVA%: -7 ± 5% vs. -3 ± 2%) fatigue was significantly greater in HTN compared with CTRL. In addition to an exaggerated MAP, LVC and QL were lower during exercise in HTN compared with CTRL. Given the critical role of QL in determining the development of neuromuscular fatigue, these hemodynamic impairments likely accounted for the faster development of neuromuscular fatigue characterizing hypertensive individuals during locomotor exercise. NEW & NOTEWORTHY The impact of primary hypertension on the cardiovascular and neuromuscular fatigue response to locomotor exercise is unknown. We compared central and peripheral hemodynamics and the development of central and peripheral fatigue during cycling exercise in patients with stage I/II hypertension and age- and activity-matched healthy individuals. In addition to a significantly elevated blood pressure, hypertensive patients were, compared with their nonhypertensive counterparts, also characterized by considerable leg blood flow limitations and impaired neuromuscular fatigue resistance.

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 ± 3 years, V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ : 49 ± 6 ml/kg/min) performed constant-load cycling exercise (∼36/43/52/98% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ ; 4 min 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% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ . 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.

On the haemodynamic consequence of the chemoreflex and muscle mechanoreflex interaction in women and men: two tales, one story.

The cardiovascular response resulting from the individual activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) is different between men and women. Whether the haemodynamic consequence resulting from the interaction of these sympathoexcitatory reflexes is also sex-dependent remains unknown. MMR and CR were activated by passive leg movement (LM) and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Twelve young men and 12 young women completed two experimental protocols: (1) resting in normoxia (PET O2 : ∼83 mmHg, PET CO2 : ∼34 mmHg), normocapnic hypoxia (PET O2 : ∼48 mmHg, PET CO2 : ∼34 mmHg) and hyperoxic hypercapnia (PET O2 : ∼524 mmHg, PET CO2 : ∼44 mmHg); (2) LM under the same gas conditions. During the MMR:O2 -CR coactivation, in men, the observed mean arterial pressure (MAP) and cardiac output (CO) were not different (additive effect), while the observed leg blood flow (LBF) and vascular conductance (LVC) were significantly lower (hypo-additive), compared with the sum of the responses elicited by each reflex alone. In women, the observed MAP was not different (additive) while the observed CO, LBF and LVC were significantly greater (hyper-additive), compared with the summated responses. During the MMR:CO2 -CR coactivation, in men, the observed MAP, CO and LBF were not different (additive), while the observed LVC was significantly lower (hypo-additive), compared with the summated responses. In women, the observed MAP was significantly higher (hyper-additive), while the observed CO, LBF and LVC were not different (additive), compared with the summated responses. The interaction of the MMR and CR has a pronounced influence on the autonomic cardiovascular control, with the haemodynamic consequences differing between men and women. KEY POINTS: The cardiovascular response resulting from the activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) was previously shown to be different between women and men; this study focused on the haemodynamic consequence of the interaction of these two sympathoexcitatory reflexes. MMR and CR were activated by passive leg movement and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Individual and interactive reflex effects on central and peripheral haemodynamics were quantified in healthy young women and men. In men, the MMR:O2 -CR and MMR:CO2 -CR interactions restricted peripheral haemodynamics, likely by potentiating sympathetic vasoconstriction. In women, the MMR:O2 -CR interaction facilitated central and peripheral haemodynamics, likely by potentiating sympathetic vasodilatation; however, the MMR:CO2 -CR interaction was simply additive for the central and peripheral haemodynamics. The interaction between the MMR and the CR exerts a profound influence on the autonomic control of cardiovascular function in humans, with the haemodynamic consequences differing between women and men.

Vascular function in continuous-flow left ventricular assist device recipients: effect of a single pulsatility treatment session.

Vascular function is further attenuated in patients with chronic heart failure implanted with a continuous-flow left ventricular assist device (LVAD), likely due to decreased arterial pulsatility, and this may contribute to LVAD-associated cardiovascular complications. However, the impact of increasing pulsatility on vascular function in this population is unknown. Therefore, 15 LVAD recipients and 15 well-matched controls underwent a 45-min, unilateral, arm pulsatility treatment, evoked by intermittent cuff inflation/deflation (2-s duty cycle), distal to the elbow. Vascular function was assessed by percent brachial artery flow-mediated dilation (%FMD) and reactive hyperemia (RH) (Doppler ultrasound). Pretreatment, %FMD (LVAD: 4.0 ± 1.7; controls: 4.2 ± 1.4%) and RH (LVAD: 340 ± 101; controls: 308 ± 94 mL) were not different between LVAD recipients and controls; however, %FMD/shear rate was attenuated (LVAD: 0.10 ± 0.04; controls: 0.17 ± 0.06%/s-1, P < 0.05). The LVAD recipients exhibited a significantly attenuated pulsatility index (PI) compared with controls prior to treatment (LVAD: 2 ± 2; controls: 15 ± 7 AU, P < 0.05); however, during the treatment, PI was no longer different (LVAD: 37 ± 38; controls: 36 ± 14 AU). Although time to peak dilation and RH were not altered by the pulsatility treatment, %FMD (LVAD: 7.0 ± 1.8; controls: 7.4 ± 2.6%) and %FMD/shear rate (LVAD: 0.19 ± 0.07; controls: 0.33 ± 0.15%/s-1) increased significantly in both groups, with, importantly, %FMD/shear rate in the LVAD recipients being restored to that of the controls pretreatment. This study documents that a localized pulsatility treatment in LVAD recipients and controls can recover local vascular function, an important precursor to the development of approaches to increase systemic pulsatility and reduce systemic vascular complications in LVAD recipients.

The exercise pressor reflex and chemoreflex interaction: cardiovascular implications for the exercising human.

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 (Sa O2 ∼79%, Pa O2 ∼43 mmHg, Pa CO2 ∼33 mmHg, pH ∼7.39), or normoxic hypercapnia (Sa O2 ∼98%, Pa O2 ∼105 mmHg, Pa CO2 ∼50 mmHg, pH ∼7.26) to modify the CR. During co-activation of the EPR and the hypoxia-induced CR (O2 -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 (CO2 -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:O2 -CR co-activation is hyper-additive for blood pressure and heart rate, and hypo-additive for peripheral haemodynamics, the interaction resulting from the EPR:CO2 -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.

On the Influence of Group III/IV Muscle Afferent Feedback on Endurance Exercise Performance.

This review discusses evidence suggesting that group III/IV muscle afferents affect locomotor performance by influencing neuromuscular fatigue. These neurons regulate the hemodynamic and ventilatory response to exercise and, thus, assure appropriate locomotor muscle O2 delivery, which optimizes peripheral fatigue development and facilitates endurance performance. In terms of central fatigue, group III/IV muscle afferents inhibit motoneuronal output and thereby limit exercise performance.

Impact of acute antioxidant administration on inflammation and vascular function in heart failure with preserved ejection fraction.

Although it is now well established that heart failure with preserved ejection fraction (HFpEF) is associated with marked inflammation and a prooxidant state that is accompanied by vascular dysfunction, whether acute antioxidant (AO) administration can effectively target these disease-related decrements has not been evaluated. Thus, the present study sought to evaluate the efficacy of an acute over-the-counter AO cocktail (600 mg α-lipoic acid, 1,000 mg vitamin C, and 600 IU vitamin E) to mitigate inflammation and oxidative stress, and subsequently improve nitric oxide (NO) bioavailability and vascular function, in patients with HFpEF. Flow-mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit vessel and microvascular function, respectively, 90 min after administration of either placebo (PL) or AO in 16 patients with HFpEF (73 ± 10 yr, EF 54-70%) using a double-blind, crossover design. Circulating biomarkers of inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde and protein carbonyl), free radical concentration (EPR spectroscopy), antioxidant capacity, ascorbate and NO bioavailability (plasma nitrate, [Formula: see text], and nitrite, [Formula: see text]) were also assessed. FMD improved following AO administration (PL: 3.49 ± 0.7%, AO: 5.83 ± 1.0%), whereas RH responses were similar between conditions (PL: 428 ± 51 mL, AO: 425 ± 51 mL). AO administration decreased CRP (PL: 4,429 ± 705 ng/mL, AO: 3,664 ± 520 ng/mL) and increased ascorbate (PL: 30.0 ± 2.9 µg/mL, AO: 45.1 ± 3.7 µg/mL) and [Formula: see text] (PL: 182 ± 21 nM, AO: 213 ± 24 nM) but did not affect other biomarkers. Together, these data suggest that acute AO administration can exert anti-inflammatory effects and improve conduit artery vasodilation, but not microvascular function, in patients with HFpEF.

Fatigue-related group III/IV muscle afferent feedback facilitates intracortical inhibition during locomotor exercise.

KEY POINTS: This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise. Firing of these interneurons probably contributes to the development of central fatigue during physical activity. ABSTRACT: We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n = 11) cycled at a comparable vastus-lateralis EMG signal (∼0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 ± 2 W) fatiguing constant-load cycling exercise (80% Wpeak; 221 ± 10 W; ∼8 min). During, PRE and POST cycling, single and paired-pulse (100 ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100 ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P < 0.05). This paralleled a reduction in conditioned MEP (P < 0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P > 0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.

Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise.

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.

Impact of age on the development of fatigue during large and small muscle mass exercise.

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 (∆Qtw, 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 ΔQtw 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, ∆Qtw 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.

Increasing relative humidity impacts low-intensity exercise in the heat.

INTRODUCTION: Many jobs require working or exercising at low intensities for extended periods in hot-humid climates; however, in these conditions the isolated effects of relative humidity (RH) remain unclear. Therefore, the purpose of this study was to examine how RH influenced thermoregulation and perception during low-intensity exercise in the heat. METHODS: There were 13 healthy men (age = 23 +/- 2 yr, mass = 83.1 +/- 13.3 kg, height = 179.9 +/- 5.9 cm, Vo2max = 55.6 +/- 7.3 ml x kg(-1) x min(-1)) who walked 90 min at 35% Vo2max in 35 degrees C, completing trials at 40% RH (40RH), 55% RH (55RH), 70% RH (70RH), and 85% RH (85RH). Investigators obtained (1) rectal temperature (Tre), skin temperatures, heart rate, and perceptual measures every 5 min; (2) respiratory measures every 30 min; and (3) pre- and post-exercise nude body masses; these measures derived partitional calorimetry variables. RESULTS: Maximal evaporative capacity and heat loss incrementally decreased as RH increased; nonevaporative and respiratory heat loss negligibly altered heat balance. Progressively raising RH significantly increased heat storage, heat production, and Tre. Tre in 40RH and 55RH matched; 70RH exceeded 40RH and 55RH after 35 min; and 85RH exceeded all trials after 40 min. DISCUSSION: Nonevaporative and respiratory heat loss mechanisms failed to offset decreased sweat evaporation. Nonlinear increases in Tre appeared to catalyze responses in most other variables, which demonstrated similar but temporally delayed patterns. Under these circumstances, an RH threshold for increased thermal strain plausibly existed between 55-70RH; environmental characteristics indicated the threshold occurred not where heat stress became uncompensable, but instead where Tre surpassed the "balance point," triggering compensatory responses.

Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus.

Introduction: One-dimensional rating scales are widely used in research and in the clinic to assess individuals' perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli. Methods: To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors. Results: Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales. Discussion: These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli.

Impact of aging on the work of breathing during exercise in healthy men.

This study examined the impact of aging on the elastic and resistive components of the work of breathing (Wb) 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 (V̇o2: 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]. Wb 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 Wb in the older group (P < 0.05), total Wb was augmented by 40%-50% during exercise at matched ventilatory and matched metabolic rates. When examined during exercise evoking similar lung volumes, total Wb was not different between the groups (P = 0.86). Taken together, although aging exaggerates total Wb 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 Wb during locomotor exercise.NEW & NOTEWORTHY This study evaluated the impact of aging on the work of breathing (Wb) 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 Wb in older participants, total Wb 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 Wb.

On the implication of dietary nitrate supplementation for the hemodynamic and fatigue response to cycling exercise.

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, V̇o2max: 42 ± 2 mL/kg/min) performed two experimental trials following 3 days of either dietary nitrate-rich beetroot juice (4.1 mmol NO3-/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 (QL; 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 (ΔQtw) 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 QL and MAP by ∼8% (P < 0.05), but did not alter LVC (P = 0.31). V̇O2 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 (ΔQtw ∼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.

Ascorbate attenuates cycling exercise-induced neuromuscular fatigue but fails to improve exertional dyspnea and exercise tolerance in COPD.

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 (ΔQtw, 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 (ΔQtw: 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 cmH2O·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.

The muscle reflex and chemoreflex interaction: ventilatory implications for the exercising human.

We examined the interactive influence of the muscle reflex (MR) and the chemoreflex (CR) on the ventilatory response to exercise. Eleven healthy subjects (5 women/6 men) completed three bouts of constant-load single-leg knee-extension exercise in a control trial and an identical trial conducted with lumbar intrathecal fentanyl to attenuate neural feedback from lower-limb group III/IV muscle afferents. The exercise during the two trials was performed while breathing ambient air ([Formula: see text] ~97%, [Formula: see text]~84 mmHg, [Formula: see text] ~32 mmHg, pH ~7.39), or under normocapnic hypoxia ([Formula: see text] ~79%, [Formula: see text] ~43 mmHg, [Formula: see text] ~33 mmHg, pH ~7.39) or normoxic hypercapnia ([Formula: see text] ~98%, [Formula: see text] ~105 mmHg, [Formula: see text] ~50 mmHg, pH ~7.26). During coactivation of the MR and the hypoxia-induced CR (O2-CR), minute ventilation (V̇e) and tidal volume (VT) were significantly greater compared with the sum of the responses to the activation of each reflex alone; there was no difference between the observed and summated responses in terms of breathing frequency (fB; P = 0.4). During coactivation of the MR and the hypercapnia-induced CR (CO2-CR), the observed ventilatory responses were similar to the summated responses of the reflexes (P ≥ 0.1). Therefore, the interaction between the MR and the O2-CR exerts a hyperadditive effect on V̇e and VT and an additive effect on fB, whereas the interaction between the MR and the CO2-CR is simply additive for all ventilatory parameters. These findings reveal that the MR:CR interaction further augments the ventilatory response to exercise in hypoxia.NEW & NOTEWORTHY Although the muscle reflex and the chemoreflex are recognized as independent feedback mechanisms regulating breathing during exercise, the ventilatory implications resulting from their interaction remain unclear. We quantified the individual and interactive effects of these reflexes during exercise and revealed differential modes of interaction. Importantly, the reflex interaction further amplifies the ventilatory response to exercise under hypoxemic conditions, highlighting a potential mechanism for optimizing arterial oxygenation in physically active humans at high altitude.

Skeletal Muscle Mitochondrial Adaptations to Maximal Strength Training in Older Adults.

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.

Non-combative taekwondo evokes highly anaerobic physiological responses in elite-level athletes: potential evidence for a new training modality.

BACKGROUND: Despite the increasing international popularity of taekwondo (TKD) poomsae, there is a lack of physiological characterizations of elite-level competitors in the sport. Thus, the aim of the present study was to investigate the physiological demands associated with various types of TKD poomsae. METHODS: Eight male international TKD poomsae competitors carried out tae-geuk (TG) and professional (PF) poomsaes (in accordance with international competition standards), and consecutive TG (CTG) poomsae (a previously identified poomsae-specific training method). During each poomsae performance, oxygen uptake, heart rate, respiratory exchange ratio, and blood lactate were measured. The physiological responses were normalized and compared to maximal aerobic exercise tests such as a graded treadmill exercise (GXT) and maximal graded arm-crank ergometer exercise (ACE) to analyze the relative exercise intensity of each TKD poomsae. RESULTS: The results showed the relative exercise intensity of TG and PF poomsaes elicit moderate to high intensity physiological proportions of the maximal responses found during the GXT and ACE tests. Interestingly, CTG poomsae responses resulted in similar exercise intensities as those reported during high intensity interval training, indicating that CTG may be an effective training modality to improve aerobic and anaerobic exercise capacity while also utilizing and developing sport specific techniques and skills. CONCLUSIONS: This indicates the need for poomsae athletes to develop and maintain both aerobic and anaerobic capacity to enhance performance. Therefore, these physiological findings will help elite poomsae competitors and coaches to develop exercise programs of substantial duration and intensity to elicit beneficial performance adaptations.

Pharmacological attenuation of group III/IV muscle afferents improves endurance performance when oxygen delivery to locomotor muscles is preserved.

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 O2 delivery. While breathing 100% O2 to ensure a similar arterial O2 content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (HCTRL) and with lumbar intrathecal fentanyl (HFENT) 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 O2 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 (ΔQtw) and voluntary activation (ΔVA), respectively. FBF (~16 mL·min-1·W-1; P = 0.6), [Formula: see text] (~24 mL O2/dL; P = 0.9), and leg O2 delivery (~0.38 mL O2·min-1·W-1; P = 0.9) were not different during HCTRL and HFENT. 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 HFENT compared with HCTRL. Quadriceps muscle activation was 9 ± 7% higher during HFENT compared with HCTRL (P < 0.05). ΔQtw was significantly greater in HFENT compared with HCTRL (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 O2 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 O2 delivery. With no difference in leg O2 delivery, afferent blockade attenuated the centrally mediated restriction in motoneuronal output and improved cycling performance.