Cerebral oxygenation during the Richalet hypoxia sensitivity test and cycling time-trial performance in severe hypoxia.

BACKGROUND: The Richalet hypoxia sensitivity test (RT), which quantifies the cardiorespiratory response to acute hypoxia during exercise at an intensity corresponding to a heart rate of ~130 bpm in normoxia, can predict susceptibility of altitude sickness. Its ability to predict exercise performance in hypoxia is unknown. OBJECTIVES: Investigate: (1) whether cerebral blood flow (CBF) and cerebral tissue oxygenation (O2Hb; oxygenated hemoglobin, HHb; deoxygenated hemoglobin) responses during RT predict time-trial cycling (TT) performance in severe hypoxia; (2) if subjects with blunted cardiorespiratory responses during RT show greater impairment of TT performance in severe hypoxia. STUDY DESIGN: Thirteen men [27 ± 7 years (mean ± SD), Wmax: 385 ± 30 W] were evaluated with RT and the results related to two 15 km TT, in normoxia and severe hypoxia (FIO2 = 0.11). RESULTS: During RT, mean middle cerebral artery blood velocity (MCAv: index of CBF) was unaltered with hypoxia at rest (p > 0.05), while it was increased during normoxic (+22 ± 12 %, p < 0.05) and hypoxic exercise (+33 ± 17 %, p < 0.05). Resting hypoxia lowered cerebral O2Hb by 2.2 ± 1.2 μmol (p < 0.05 vs. resting normoxia); hypoxic exercise further lowered it to -7.6 ± 3.1 μmol below baseline (p < 0.05). Cerebral HHb, increased by 3.5 ± 1.8 μmol in resting hypoxia (p < 0.05), and further to 8.5 ± 2.9 μmol in hypoxic exercise (p < 0.05). Changes in CBF and cerebral tissue oxygenation during RT did not correlate with TT performance loss (R = 0.4, p > 0.05 and R = 0.5, p > 0.05, respectively), while tissue oxygenation and SaO2 changes during TT did (R = -0.76, p < 0.05). Significant correlations were observed between SaO2, MCAv and HHb during RT (R = -0.77, -0.76 and 0.84 respectively, p < 0.05 in all cases). CONCLUSIONS: CBF and cerebral tissue oxygenation changes during RT do not predict performance impairment in hypoxia. Since the changes in SaO2 and brain HHb during the TT correlated with performance impairment, the hypothesis that brain oxygenation plays a limiting role for global exercise in conditions of severe hypoxia remains to be tested further

Resting EEG Microstates and Autonomic Heart Rate Variability Do Not Return to Baseline One Hour After a Submaximal Exercise.

Recent findings suggest that an acute physical exercise modulates the temporal features of the EEG resting microstates, especially the microstate map C duration and relative time coverage. Microstate map C has been associated with the salience resting state network, which is mainly structured around the insula and cingulate, two brain nodes that mediate cardiovascular arousal and interoceptive awareness. Heart rate variability (HRV) is dependent on the autonomic balance; specifically, an increase in the sympathetic (or decrease in the parasympathetic) tone will decrease variability while a decrease in the sympathetic (or increase in the parasympathetic) tone will increase variability. Relying on the functional interaction between the autonomic cardiovascular activity and the salience network, this study aims to investigate the effect of exercise on the resting microstate and the possible interplay with this autonomic cardiovascular recovery after a single bout of endurance exercise. Thirty-eight young adults performed a 25-min constant-load cycling exercise at an intensity that was subjectively perceived as "hard." The microstate temporal features and conventional time and frequency domain HRV parameters were obtained at rest for 5 min before exercise and at 5, 15, 30, 45, and 60 min after exercise. Compared to the baseline, all HRV parameters were changed 5 min after exercise cessation. The mean durations of microstate B and C, and the frequency of occurrence of microstate D were also changed immediately after exercise. A long-lasting effect was found for almost all HRV parameters and for the duration of microstate C during the hour following exercise, indicating an uncompleted recovery of the autonomic cardiovascular system and the resting microstate. The implication of an exercise-induced afferent neural traffic is discussed as a potential modulator of both the autonomic regulation of heart rate and the resting EEG microstate

Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery.

During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia

Effects of COVID-19 lockdown on heart rate variability.

Strict lockdown rules were imposed to the French population from 17 March to 11 May 2020, which may result in limited possibilities of physical activity, modified psychological and health states. This report is focused on HRV parameters kinetics before, during and after this lockdown period. 95 participants were included in this study (27 women, 68 men, 37 ± 11 years, 176 ± 8 cm, 71 ± 12 kg), who underwent regular orthostatic tests (a 5-minute supine followed by a 5-minute standing recording of heart rate (HR)) on a regular basis before (BSL), during (CFN) and after (RCV) the lockdown. HR, power in low- and high-frequency bands (LF, HF, respectively) and root mean square of the successive differences (RMSSD) were computed for each orthostatic test, and for each position. Subjective well-being was assessed on a 0-10 visual analogic scale (VAS). The participants were split in two groups, those who reported an improved well-being (WB+, increase >2 in VAS score) and those who did not (WB-) during CFN. Out of the 95 participants, 19 were classified WB+ and 76 WB-. There was an increase in HR and a decrease in RMSSD when measured supine in CFN and RCV, compared to BSL in WB-, whilst opposite results were found in WB+ (i.e. decrease in HR and increase in RMSSD in CFN and RCV; increase in LF and HF in RCV). When pooling data of the three phases, there were significant correlations between VAS and HR, RMSSD, HF, respectively, in the supine position; the higher the VAS score (i.e., subjective well-being), the higher the RMSSD and HF and the lower the HR. In standing position, HRV parameters were not modified during CFN but RMSSD was correlated to VAS. Our results suggest that the strict COVID-19 lockdown likely had opposite effects on French population as 20% of participants improved parasympathetic activation (RMSSD, HF) and rated positively this period, whilst 80% showed altered responses and deteriorated well-being. The changes in HRV parameters during and after the lockdown period were in line with subjective well-being responses. The observed recordings may reflect a large variety of responses (anxiety, anticipatory stress, change on physical activity…) beyond the scope of the present study. However, these results confirmed the usefulness of HRV as a non-invasive means for monitoring well-being and health in this population

Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles

The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on-1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on-3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased "voluntary activation." In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT

Minimal window duration for accurate HRV recording in athletes

Heart rate variability (HRV) is non-invasive and commonly used for monitoring responses to training loads, fitness, or overreaching in athletes. Yet, the recording duration for aseries of RR-intervals varies from 1 to 15 min in the literature. The aim of the present work was to assess the minimum record duration to obtain reliableHRV results. RR-intervalsfrom 159 orthostatic tests (7 min supine, SU, followed by 6 min standing, ST) were analyzed. Reference windows were 4 min in SU (min 3–7) and 4 min in ST (min 9–13).Those windows were subsequently divided and the analyses were repeated on eight different fractioned windows: the first min (0–1), the second min (1–2), the third min (2–3),the fourth min (3–4), the first 2 min (0–2), the last 2 min (2–4), the first 3 min (0–3), and thelast 3 min (1–4). Correlation and Bland & Altman statistical analyses were systematically performed. The analysis window could be shortened to 0–2 instead of 0–4 for RMSSD only, whereas the 4-min window was necessary for LF and total power. Since there is a need for 1 min of baseline to obtain a steady signal prior the analysis window, we conclude that studies relying on RMSSD may shorten the windows to 3 min (=1+2)in SU or seated position only and to 6 min (=1+2 min SU plus 1+2 min ST) if there is an orthostatic test. Studies relying on time- and frequency-domain parameters need a minimum of 5 min (=1+4) min SU or seated position only but require 10 min (=1+4 minSU plus 1+4 min ST) for the orthostatic tes

Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial.

BACKGROUND: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. METHODS: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. RESULTS: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). CONCLUSION: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia

Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre-term-born adults.

Pre-term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre-term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg <sup>-1</sup> min <sup>-1</sup> ) with 16 well-matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg <sup>-1</sup> min <sup>-1</sup> ). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO <sub>2</sub> ), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O <sub>2</sub> and CO <sub>2</sub> were similar in pre-term and full-term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 ). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre-term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end-tidal CO <sub>2</sub> with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term-born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli. KEY POINTS: Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre-term birth. Whether pre-term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term-born individuals. According to the present data, there is no difference between healthy pre-term and well-matched term-born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia. Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia. The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre-term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments

Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises.

Neuropeptide Y 1-36 (NPY1-36) is a vasoconstrictor peptide co-secreted with norepinephrine (NE) by nerve endings during sympathetic activation. NPY1-36 potentiates NE action post-synaptically through the stimulation of the Y1 receptor, whereas its metabolite NPY3-36 resulting from DPP4 action activates Y2 presynaptic receptors, inhibiting NE and acetylcholine secretion. The secretions of NPY1-36 and NPY3-36 in response to sympathetic nervous system activation have not been studied due to the lack of analytical techniques available to distinguish them. We determined in healthy volunteers NPY1-36, NPY3-36 and catecholamine kinetics and how these neurotransmitters modulate the physiological stress response during and after moderate- and heavy-intensity exercises. Six healthy males participated in this randomized, double-blind, saxagliptin vs placebo crossover study. The volunteers performed an orthostatic test, a 30-min exercise at moderate intensity and a 15-min exercise at heavy intensity each followed by 50 min of recovery in two separate sessions with saxagliptin or placebo. Oxygen consumption (V̇O <sub>2</sub> ), ventilation and heart rate were continuously recorded. NE, epinephrine, NPY1-36 and NPY3-36 were quantified by tandem mass spectrometry. We found that exercise triggers NPY1-36 and NE secretion in an intensity-dependent manner and that NE returns faster to the baseline concentration than NPY1-36 after exercise. NPY3-36 rises during recovery parallel to the decline of NPY1-36. Saxagliptin reverses the NPY1-36/NPY3-36 ratio but does not affect hemodynamics, nor NPY1-36 and catecholamine concentrations. We found that NPY1-36 half-life is considerably shorter than previously established with immunoassays. NPY1-36 and NE secretions are finely regulated to prevent an excessive physiological Y1 stimulating response to submaximal exercise