A randomized sham-controlled trial on the effect of continuous positive airway pressure treatment on gait control in severe obstructive sleep apnea patients.

To determine the effect of continuous positive airway pressure (CPAP), the gold standard treatment for obstructive sleep apnea syndrome (OSAS), on gait control in severe OSAS patients. We conducted a randomized, double-blind, parallel-group, sham-controlled monocentric study in Grenoble Alpes University Hospital, France. Gait parameters were recorded under single and dual-task conditions using a visuo-verbal cognitive task (Stroop test), before and after the 8-week intervention period. Stride-time variability, a marker of gait control, was the primary study endpoint. Changes in the determinants of gait control were the main secondary outcomes. ClinicalTrials.gov Identifier: (NCT02345694). 24 patients [median (Q1; Q3)]: age: 59.5 (46.3; 66.8) years, 87.5% male, body mass index: 28.2 (24.7; 29.8) kg. m-2, apnea-hypopnea index: 51.6 (35.0; 61.4) events/h were randomized to be treated by effective CPAP (n = 12) or by sham-CPAP (n = 12). A complete case analysis was performed, using a mixed linear regression model. CPAP elicited no significant improvement in stride-time variability compared to sham-CPAP. No difference was found regarding the determinants of gait control. This study is the first RCT to investigate the effects of CPAP on gait control. Eight weeks of CPAP treatment did not improve gait control in severe non-obese OSAS patients. These results substantiate the complex OSAS-neurocognitive function relationship.

Synergetic Effect of NO Precursor Supplementation and Exercise Training.

INTRODUCTION: Nitric oxide (NO) precursor supplementation has been shown to increase NO bioavailability and can potentially improve vascular function and exercise performance. It remains unclear whether the combination of NO precursor supplementation and exercise training has synergic effects on exercise performance. This study aims to assess the effect of chronic nitrate and citrulline intake on exercise training adaptations in healthy young individuals. METHODS: In this randomized, double-bind trial, 24 healthy young (12 females) subjects performed vascular function assessment (blood pressure, pulse wave velocity, postischemia vasodilation, and cerebrovascular reactivity) and both local (submaximal isometric unilateral knee extension) and whole-body (incremental cycling) exercise tests to exhaustion before and after a 2-month exercise training program and daily intake of a placebo or a nitrate-rich salad and citrulline (N + C, 520 mg nitrate and 6 g citrulline) drink. Prefrontal cortex and quadriceps oxygenation was monitored continuously during exercise by near-infrared spectroscopy. RESULTS: N + C supplementation had no effect on vascular function and muscle and cerebral oxygenation during both local and whole-body exercise. N + C supplementation induced a significantly larger increase in maximal knee extensor strength (+5.1 ± 3.5 vs +0.2 ± 5.5 kg, P = 0.008) as well as a trend toward a larger increase in knee extensor endurance (+35.2 ± 26.1 vs +24.0 ± 10.4 contractions, P = 0.092) than placebo, but no effect on exercise training-induced maximal aerobic performance improvement. CONCLUSION: These results suggest that chronic nitrate and citrulline supplementation enhances the effect of exercise training on quadriceps muscle function in healthy active young individuals, but this does not translate into improved maximal aerobic performances.

Fatigue and Recovery after Single-Stage versus Multistage Ultramarathon Running.

PURPOSE: Ultramarathon running includes two main types of events: single-stage race (SSR) and multistage races (MSR). Direct comparison of neuromuscular fatigue and recovery after SSR versus MSR race of comparable distance and elevation has never been performed. The aim of this study was to assess neuromuscular fatigue and recovery after two ultramarathons of equal distance performed either (i) in a single stage or (ii) in four successive days. METHODS: Thirty-one runners participated in the study: 17 ran 169 km in a single-stage race and 14 performed around 40 km·d over 4 d. The two races were performed on the same course. Neuromuscular function was tested before (PRE), after (POST), and 2 (D + 2), 5 (D + 5) and 10 (D + 10) days after the races. Neuromuscular function was evaluated on both knee extensors (KE) and plantar flexors (PF) with voluntary and evoked contractions using electrical (femoral and tibial, respectively) nerve stimulation. RESULTS: Reduction of voluntary activation measured in the KE was greater (i.e., central fatigue) for SSR than MSR directly after the race (-23% vs -7%), P < 0.01). Reductions in evoked mechanical KE and PF responses on relaxed muscle (i.e., peripheral fatigue) of both KE and PF took longer to recover in MSR than in SSR. CONCLUSIONS: Performing prolonged running exercise over several days, each separated by rest, elicits more prolonged impairments in contractile function compared with single-stage ultramarathon, whereas single-stage mountain ultramarathon ran on the same course is associated with greater central fatigue.

Effect of chronic nitrate and citrulline supplementation on vascular function and exercise performance in older individuals.

Increased nitric oxide (NO) bioavailability may improve exercise performance and vascular function. It remains unclear whether older adults who experience a decreased NO bioavailability may benefit from chronic NO precursor supplementation. This randomised, double-blind, trial aims to assess the effect of chronic NO precursor intake on vascular function and exercise performance in older adults (60-70 years old). Twenty-four healthy older adults (12 females) performed vascular function assessment and both local (knee extensions) and whole-body (incremental cycling) exercise tests to exhaustion before and after one month of daily intake of a placebo (PLA) or a nitrate-rich salad and citrulline (N+C, 520mg nitrate and 6g citrulline) drink. Arterial blood pressure (BP) and stiffness, post-ischemic, hypercapnic and hypoxic vascular responses were evaluated. Prefrontal cortex and quadriceps oxygenation was monitored by near-infrared spectroscopy. N+C supplementation reduced mean BP (-3.3mmHg; p=0.047) without altering other parameters of vascular function and oxygenation kinetics. N+C supplementation reduced heart rate and oxygen consumption during submaximal cycling and increased maximal power output by 5.2% (p<0.05), but had no effect on knee extension exercise performance. These results suggest that chronic NO precursor supplementation in healthy older individuals can reduce resting BP and increase cycling performance by improving cardiorespiratory responses.

Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men.

NEW FINDINGS: What is the central question of this study? What is the effect of acute NO precursor intake on vascular function, muscle and cerebral oxygenation and peripheral and central neuromuscular fatigue during knee-extension exercise? What is the main finding and its importance? Acute NO precursor ingestion increases the plasma concentrations of NO precursors (nitrate, arginine and citrulline) and enhances post-ischaemic vasodilatation, but has no significant effect on muscle and cerebral oxygenation, peripheral and central mechanisms of neuromuscular fatigue and, consequently, does not improve exercise performance. ABSTRACT: Nitric oxide (NO) plays an important role in matching blood flow to oxygen demand in the brain and contracting muscles during exercise. Previous studies have shown that increasing NO bioavailability can improve muscle function. The aim of this study was to assess the effect of acute NO precursor intake on muscle and cerebral oxygenation and on peripheral and central neuromuscular fatigue during exercise. In four experimental sessions, 15 healthy men performed a thigh ischaemia-reperfusion test followed by submaximal isometric knee extensions (5 s on-4 s off; 45% of maximal voluntary contraction) until task failure. In each session, subjects drank a nitrate-rich beetroot juice containing 520 mg nitrate (N), N and citrulline (6 g; N+C), N and arginine (6 g; N+A) or a placebo (PLA). Prefrontal cortex and quadriceps near-infrared spectroscopy parameters were monitored continuously. Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. The post-ischaemic increase in thigh blood total haemoglobin concentration was larger in N (10.1 ± 3.7 mmol) and N+C (10.9 ± 3.3 mmol) compared with PLA (8.2 ± 2.7 mmol; P < 0.05). Nitric oxide precursors had no significant effect on muscle and cerebral oxygenation or on peripheral and central mechanisms of neuromuscular fatigue during exercise. The total number of knee extensions did not differ between sessions (N, 71.9 ± 33.2; N+A, 73.3 ± 39.4; N+C, 74.6 ± 34.0; PLA, 71.8 ± 39.9; P > 0.05). In contrast to the post-ischaemic hyperaemic response, NO bioavailability in healthy subjects might not be the limiting factor for tissue perfusion and oxygenation during submaximal knee extensions to task failure.

Neuromuscular Dysfunction and Cortical Impairment in Sleep Apnea Syndrome.

PURPOSE: Lower muscle strength and endurance have been reported in severe obstructive sleep apnea (OSA). Increased intracortical inhibition previously reported at rest in OSA suggests central neuromuscular impairments in these patients. We hypothesized that (i) OSA patients demonstrate reduced knee extensor strength and endurance due to central impairments and (ii) continuous positive airway pressure (CPAP) treatment improves neuromuscular function in these patients. METHODS: Twelve OSA patients and 11 healthy controls performed intermittent knee extensions until task failure before and after 8 wk of CPAP treatment or control period. Maximal voluntary contraction, voluntary activation and corticospinal excitability and inhibition assessed by single- and paired-pulse transcranial magnetic stimulation were measured before and during the fatiguing task. RESULTS: Time to exhaustion was lower in OSA (before CPAP treatment: 1008 ± 549 s; after CPAP treatment: 975 ± 378 s) compared with controls (before control period: 1476 ± 633 s; after control period: 1274 ± 506 s; P = 0.017). Obstructive sleep apnea patients had reduced maximal voluntary contraction and VATMS compared with controls throughout the fatiguing task as well as increased intracortical inhibition (all P < 0.05). Continuous positive airway pressure treatment did not induce any changes in neuromuscular function (P > 0.05 for all parameters). CONCLUSIONS: This study demonstrates that severe OSA patients have cortical impairments which are likely contributing to their reduced knee extensors strength and endurance. Both cortical impairments and neuromuscular function are not improved after 8 wk of CPAP treatment.

Effects of Acute Salbutamol Intake on Peripheral and Central Fatigue in Trained Men.

PURPOSE: Ergogenic effect in physically active subjects has been reported after acute salbutamol (SAL) intake. ß2-Agonists have potential stimulant effects within the central nervous system that could be involved in this ergogenic effect. We hypothesized that acute SAL intake would induce changes in cerebral responses during exercise, with significant improvement in cerebral oxygenation and voluntary activation (VA) contributing to an increase in muscle performance. METHODS: Fourteen trained male subjects (25 ± 5 yr) performed repeated isometric knee extensions until task failure (TF) after 4 mg (oral) SAL, 800 µg (inhaled) SAL, or placebo intake. VA, corticospinal excitability, and inhibition assessed by transcranial magnetic stimulation and changes in hemoglobin concentrations assessed by near-infrared spectroscopy were measured before and during the fatiguing task. RESULTS: SAL had no significant effect both at rest and during exercise on prefrontal cortex oxygenation (e.g., changes in oxyhemoglobin concentration at TF: 11.4 ± 11.1 (4 mg SAL) vs 10.4 ± 10.6 (800 µg SAL) vs 10.8 ± 8.1 µmol (placebo); P = 0.314) and neuromuscular function (e.g., VA measured by TMS at TF: 90.2% ± 6.6% vs 92.6% ± 5.0% vs 90.1% ± 7.0%; P = 0.760). SAL had no effect on the number of contractions until TF (95 ± 51 vs 100 ± 52 vs 93 ± 47; P = 0.629). CONCLUSIONS: These results indicate that acute SAL intake had no effect on central and peripheral mechanisms of neuromuscular fatigue and did not improve quadriceps endurance.

Effects of high-altitude exposure on supraspinal fatigue and corticospinal excitability and inhibition.

PURPOSE: While acute hypoxic exposure enhances exercise-induced central fatigue and can alter corticospinal excitability and inhibition, the effect of prolonged hypoxic exposure on these parameters remains to be clarified. We hypothesized that 5 days of altitude exposure would (i) normalize exercise-induced supraspinal fatigue during isolated muscle exercise to sea level (SL) values and (ii) increase corticospinal excitability and inhibition. METHODS: Eleven male subjects performed intermittent isometric elbow flexions at 50% of maximal voluntary contraction to task failure at SL and after 1 (D1) and 5 (D5) days at 4350 m. Transcranial magnetic stimulation and peripheral electrical stimulation were used to assess supraspinal and peripheral fatigues. Pre-frontal cortex and biceps brachii oxygenation was monitored by near-infrared spectroscopy. RESULTS: Exercise duration was not statistically different between SL (1095 ± 562 s), D1 (1132 ± 516 s), and D5 (1440 ± 689 s). No significant differences were found between the three experimental conditions in maximal voluntary activation declines at task failure (SL -16.8 ± 9.5%; D1 -25.5 ± 11.2%; D5 -21.8 ± 7.0%; p > 0.05). Exercise-induced peripheral fatigue was larger at D5 versus SL (100 Hz doublet at task failure: -58.8 ± 16.6 versus -41.8 ± 20.1%; p < 0.05). Corticospinal excitability at 50% maximal voluntary contraction was lower at D5 versus SL (brachioradialis p < 0.05, biceps brachii p = 0.055). Cortical silent periods were shorter at SL versus D1 and D5 (p < 0.05). CONCLUSIONS: The present results show similar patterns of supraspinal fatigue development during isometric elbow flexions at SL and after 1 and 5 days at high altitude, despite larger amount of peripheral fatigue at D5, lowered corticospinal excitability and enhanced corticospinal inhibition at altitude.

Effect of acute nitrate and citrulline supplementation on muscle microvascular response to ischemia-reperfusion in healthy humans.

Nitric oxide (NO) is implicated in vasomotor control mechanisms altering the diameter of the vessels under various physiological and pathological conditions. There are 2 main NO production pathways, 1 NO synthase (NOS) independent (nitrate-nitrite-NO) and the other is NOS dependent (citrulline-arginine-NO). The objective of the study was to evaluate the effect of acute nitrate and citrulline supplementation on post-ischemic vascular response in healthy subjects. Fourteen subjects performed 2-leg vascular occlusion tests, 3 days apart. They were randomly assigned to consume a drink containing 1200 mg (19.4 mmol) of nitrate and 6 g of citrulline (N+C) or a placebo (Pl). Changes in total hemoglobin (Hbtot) and oxyhemoglobin (HbO2) concentrations were recorded by near-infrared spectroscopy on the thigh and calf muscles. No differences between N+C and Pl were observed during the ischemic period. Hbtot increased to a larger extent during the reperfusion period for the thigh (e.g., area under the curve, 821 ± 324 vs. 627 ± 381 mmol·s-1, p = 0.003) and the calf (515 ± 285 vs. 400 ± 275 mmol·s-1, p = 0.029) in the N+C versus Pl conditions. Similar results were found regarding HbO2 for the thigh (e.g., area under the curve, 842 ± 502 vs. 770 ± 491 mmol·s-1, p = 0.077) and the calf (968 ± 536 vs. 865 ± 275 mmol·s-1, p = 0.075). The larger postocclusive Hbtot and HbO2 responses observed after N+C intake suggests a greater post-ischemic vasodilation, which may be due to increased NO availability, via the activation of the 2 main NO production pathways.