Publications by authors named "Joshua C Weavil"

We examined the interactive influence of hypoxia and exercise, and hypercapnia and exercise, on regional cerebral perfusion and sympathetic activation. Twenty healthy young adults (seven women) completed study trials including (1) rest in normoxia ( : ∼96%, : ∼36 mmHg), normocapnic hypoxia ( : ∼84%, : ∼36 mmHg), and normoxic hypercapnia ( : ∼98%, : ∼46 mmHg) and (2) unilateral rhythmic handgrip exercise (45% of maximal voluntary contraction at 1 Hz for 3 min) under the same gas conditions. Based on the exercising arm, blood flow in the contralateral internal carotid (ICA) and ipsilateral vertebral (VA) arteries, anterior and posterior cerebral O delivery ( ), and muscle sympathetic nerve activity (MSNA) were measured in each trial.

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Article Synopsis
  • - Sarcopenia, a condition involving muscle loss, is common in men with liver cirrhosis and has negative effects on health, including increasing the risk of hepatic encephalopathy (HE); androgen receptor agonists (ARAs) like LPCN 1148 show potential to address these issues but their effectiveness and safety in this demographic were previously unclear.
  • - In a phase 2 trial, men with cirrhosis and sarcopenia were given either LPCN 1148 or placebo for 24 weeks, with results indicating that those taking LPCN 1148 had a significant increase in muscle mass (measured by CT scans) and experienced fewer episodes of serious HE compared to the placebo group.
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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, : 46 (8) ml/kg/min) performed consecutive constant-load cycling bouts at ∼50% (20 min), ∼75% (20 min) and ∼100% (5 min) 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.

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Patients with hypertension (HTN) are characterized by exaggerated vascular resistance and mean arterial pressure (MAP) and a compromised leg blood flow (Q) 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 Q, 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).

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Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization ( ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and leg to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs.

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We investigated the role of the exercise pressor reflex (EPR) in regulating the haemodynamic response to locomotor exercise. Eight healthy participants (23 ± 3 years, : 49 ± 6 ml/kg/min) performed constant-load cycling exercise (∼36/43/52/98% ; 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.

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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 (O -CR) or hypercapnia (CO -CR), respectively.

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The exercise pressor reflex (EPR), a neurocirculatory control mechanism, is exaggerated in hypertensive humans and rats. Disease-related abnormalities within the afferent arm of the reflex loop, including mechano- and metabosensitive receptors located at the terminal end of group III/IV muscle afferents, may contribute to the dysfunctional EPR in hypertension. Using control (WKY) and spontaneous hypertensive (SHR) rats, we examined dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized as significant determinants of the EPR.

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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 ( P-MRS) was used to continuously quantify intramuscular [H ] and [Pi] during both trials.

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The role of nitric oxide (NO) as a modulator of functional sympatholysis has been debated in the literature, but the preponderance of evidence suggests that the magnitude of NO-mediated dilation is restrained by sympathetic vasoconstriction. Therefore, we hypothesized that passive leg movement (PLM)-induced vasodilation, which is predominantly NO-mediated, would be attenuated by an exercise-induced increase in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA, leg blood flow (LBF), and mean arterial blood pressure (MAP) were measured and leg vascular conductance (LVC) calculated in 9 healthy subjects (30 ± 3 yr), during PLM with and without sympathoexcitation evoked by arm-cranking exercise (ACE), at 25, 50, and 75% of maximal capacity.

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This study examined the impact of aging on the elastic and resistive components of the work of breathing () during locomotor exercise at a given ) ventilatory rate, ) metabolic rate, and ) 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), similar metabolic rates (V̇o: approximately 1.2, 1.

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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: 42 ± 2 mL/kg/min) performed two experimental trials following 3 days of either dietary nitrate-rich beetroot juice (4.1 mmol NO/day; DNS) or placebo (PLA) supplementation in a blinded, counterbalanced order.

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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.

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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.

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This short review offers a general summary of the consequences of whole body exercise on neuromuscular fatigue pertaining to the locomotor musculature. Research from the past two decades have shown that whole body exercise causes considerable peripheral and central fatigue. Three determinants characteristic for locomotor exercise are discussed, namely, pulmonary system limitations, neural feedback mechanisms, and mental/psychological influences.

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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.

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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.

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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).

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Recognizing the age-related decline in skeletal muscle feed artery (SMFA) vasodilatory function, this study examined the link between vasodilatory and mitochondrial respiratory function in the human vasculature. Twenty-four SMFAs were harvested from young (35 ± 6 yr, = 9) and old (71 ± 9 yr, = 15) subjects. Vasodilation in SMFAs was assessed, by pressure myography, in response to flow-induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP) while mitochondrial respiration was measured, by respirometry, in permeabilized SMFAs.

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We investigated the impact of hypertension on circulatory responses to exercise and the role of the exercise pressor reflex in determining the cardiovascular abnormalities characterizing patients with hypertension. After a 7-day drug washout, 8 hypertensive (mean arterial pressure [MAP] 130±4 mm Hg; 65±3 years) and 8 normotensive (MAP 117±2 mm Hg; 65±2 years) individuals performed single-leg knee-extensor exercise (7 W, 15 W, 50%, 80%-W) under control conditions and with lumbar intrathecal fentanyl impairing feedback from µ-opioid receptor-sensitive leg muscle afferents. Femoral artery blood flow (Q), MAP (femoral artery), leg vascular conductance, and changes in cardiac output were continuously measured.

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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 delivery. While breathing 100% O to ensure a similar arterial O content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (H) and with lumbar intrathecal fentanyl (H) 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.

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The corticospinal pathway is considered the primary conduit for voluntary motor control in humans. The efficacy of the corticospinal pathway to relay neural signals from higher brain areas to the locomotor muscle, i.e.

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Little is known about vascular mitochondrial respiratory function and the impact of age. Therefore, skeletal muscle feed arteries were harvested from young (33 ± 7 yr, n = 10), middle-aged (54 ± 5 yr, n = 10), and old (70 ± 7 yr, n = 10) subjects, and mitochondrial respiration as well as citrate synthase (CS) activity were assessed. Complex I (CI) and complex I + II (CI+II) state 3 respiration were greater in young (CI: 10.

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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.

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