Acute high-intensity exercise and skeletal muscle mitochondrial respiratory function: role of metabolic perturbation.

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.

Nitric oxide synthase inhibition with N(G)-monomethyl-l-arginine: Determining the window of effect in the human vasculature.

Nitric oxide synthase (NOS) inhibition with N(G)-monomethyl-l-arginine (L-NMMA) is often used to assess the role of NO in human cardiovascular function. However, the window of effect for L-NMMA on human vascular function is unknown, which is critical for designing and interpreting human-based studies. This study utilized the passive leg movement (PLM) assessment of vascular function, which is predominantly NO-mediated, in 7 young male subjects under control conditions, immediately following intra-arterial L-NMMA infusion (0.

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.

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 role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension.

Key Points: Exercise in patients with hypertension can be accompanied by an abnormal cardiovascular response that includes attenuated blood flow and an augmented pressor response. Endothelin-1, a very potent vasoconstrictor, is a key modulator of blood flow and pressure during in health and has been implicated as a potential cause of the dysfunction in hypertension. We assessed the role of endothelin-1, acting through endothelin A (ET ) receptors, in modulating the central and peripheral cardiovascular responses to exercise in patients with hypertension via local antagonism of these receptors during exercise.

Exercise Pressor Reflex Contributes to the Cardiovascular Abnormalities Characterizing: Hypertensive Humans During Exercise.

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.

Influence of group III/IV muscle afferents on small muscle mass exercise performance: a bioenergetics perspective.

Key Points: This investigation assessed the influence of group III/IV muscle afferents on small muscle mass exercise performance from a skeletal muscle bioenergetics perspective. Group III/IV muscle afferent feedback was attenuated with lumbar intrathecal fentanyl during intermittent isometric single-leg knee-extensor all-out exercise, while P-MRS was used to assess skeletal muscle bioenergetics. Attenuation of group III/IV muscle afferent feedback improved exercise performance during the first minute of exercise, due to an increase in total ATP production with no change in the ATP cost of contraction.

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.

Single passive leg movement assessment of vascular function: contribution of nitric oxide.

Broxterman RM, Trinity JD, Gifford JR, Kwon OS, Kithas AC, Hydren JR, Nelson AD, Morgan DE, Jessop JE, Bledsoe AD, Richardson RS. Single passive leg movement assessment of vascular function: contribution of nitric oxide. J Appl Physiol 123: 1468-1476, 2017.

Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents.

Purpose: The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation.

Methods: Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (P-MRS).

Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans.

Key Points: The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise-induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural 'drive' to working locomotor muscle and limits the exercise-induced intramuscular metabolic perturbation.

Endogenous endothelin-1 and femoral artery shear rate: impact of age and implications for atherosclerosis.

Background: Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate.

Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans.

We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined.

Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration.

Endothelin-A-mediated vasoconstriction during exercise with advancing age.

The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123.

Taming the "sleeping giant": the role of endothelin-1 in the regulation of skeletal muscle blood flow and arterial blood pressure during exercise.

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O(2) difference, leg O(2) consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ET(A)) receptor antagonist].

GlideScope versus flexible fiber optic for awake upright laryngoscopy.

Study Objectives: We compare laryngoscopic quality and time to highest-grade view between a face-to-face approach with the GlideScope and traditional flexible fiber-optic laryngoscopy in awake, upright volunteers.

Methods: This was a prospective, randomized, crossover study in which we performed awake laryngoscopy under local anesthesia on 23 healthy volunteers, using both a GlideScope video laryngoscopy face-to-face technique with the blade held upside down and flexible fiber-optic laryngoscopy. Operator reports of Cormack-Lehane laryngoscopic views and video-reviewed time to highest-grade view, as well as number of attempts, were recorded.