Fitness Level- and Sex-Related Differences in Pulmonary Limitations to Maximal Exercise in Normoxia and Hypoxia.

PURPOSE: Both maximal-intensity exercise and altitude exposure challenge the pulmonary system that may reach its maximal capacities. Expiratory flow limitation (EFL) and exercise-induced hypoxemia (EIH) are common in endurance-trained athletes. Furthermore, due to their smaller airways and lung size, women, independently of their fitness level, may be more prone to pulmonary limitations during maximal-intensity exercise; particularly when performed in hypoxic conditions. The objective of this study was to investigate the impact of sex and fitness level on pulmonary limitations during maximal exercise in normoxia and their consequences in acute hypoxia. METHODS: Fifty-one participants were distributed across four different groups according to sex and fitness level. Participants visited the laboratory on three occasions to perform maximal incremental cycling tests in normoxia and hypoxia (inspired oxygen fraction = 0.14) and two hypoxic chemosensitivity tests. Pulmonary function and ventilatory capacities were evaluated at each visit. RESULTS: EIH was more prevalent (62.5% vs. 22.2%, p = 0.004) and EFL less common (37.5% vs. 70.4%, p = 0.019) in women than men. EIH prevalence was different (p = 0.004) between groups of trained men (41.7%), control men (6.7%), trained women (50.0%), and control women (75.0%). All EIH men but only 40% of EIH women exhibited EFL. EFL individuals had higher slope ratio (p = 0.029), higher ventilation (V̇E) (p < 0.001), larger ΔVO2max (p = 0.019) and lower hypoxia-related V̇E increase (p < 0.001). CONCLUSIONS: Women reported a higher EIH prevalence than men, regardless of their fitness level, despite a lower EFL prevalence. EFL seems mainly due to the imbalance between ventilatory demands and capacities. It restricts ventilation, leading to a larger performance impairment during maximal exercise in hypoxic conditions.

Baroreflex sensitivity is blunted in hypoxia independently of changes in inspired carbon dioxide pressure in prematurely born male adults.

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high-altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age-matched term born adults (40 ± 0 weeks) underwent consecutive 6-min stages breathing different oxygen and carbon dioxide concentrations at both sea-level and high-altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2 ), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2 ), and hypobaric hypoxia with end-tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg-1 , main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg-1 , p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg-1 , p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high-altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults.

Hot water immersion: Maintaining core body temperature above 38.5°C mitigates muscle fatigue.

PURPOSE: Hot water immersion (HWI) has gained popularity to promote muscle recovery, despite limited data on the optimal heat dose. The purpose of this study was to compare the responses of two exogenous heat strains on core body temperature, hemodynamic adjustments, and key functional markers of muscle recovery following exercise-induced muscle damage (EIMD). METHODS: Twenty-eight physically active males completed an individually tailored EIMD protocol immediately followed by one of the following recovery interventions: HWI (40°C, HWI40 ), HWI (41°C, HWI41 ) or warm water immersion (36°C, CON36 ). Gastrointestinal temperature (Tgi ), hemodynamic adjustments (cardiac output [CO], mean arterial pressure [MAP], and systemic vascular resistance [SVR]), pre-frontal cortex deoxyhemoglobin (HHb), ECG-derived respiratory frequency, and subjective perceptual measures were tracked throughout immersion. In addition, functional markers of muscle fatigue (maximal concentric peak torque [Tpeak ]) and muscle damage (late-phase rate of force development [RFD100-200 ]) were measured prior to EIMD (pre-), 24 h (post-24 h), and 48 h (post-48 h) post-EIMD. RESULTS: By the end of immersion, HWI41 led to significantly higher Tgi values than HWI40 (38.8 ± 0.1 vs. 38.0°C ± 0.6°C, p < 0.001). While MAP was well maintained throughout immersion, only HWI41 led to increased (HHb) (+4.2 ± 1.47 µM; p = 0.005) and respiratory frequency (+4.0 ± 1.21 breath.min-1 ; p = 0.032). Only HWI41 mitigated the decline in RFD100-200 at post-24 h (-7.1 ± 31.8%; p = 0.63) and Tpeak at post-48 h (-3.1 ± 4.3%, p = 1). CONCLUSION: In physically active males, maintaining a core body temperature of ~25 min within the range of 38.5°C-39°C has been found to be effective in improving muscle recovery, while minimizing the risk of excessive physiological heat strain.

Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia.

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia.

Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning.

The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2 days at high altitude (3375 m), 16 young preterm-born (gestational age, 29 ± 1 weeks) and 15 age-matched term-born (40 ± 0 weeks) adults were exposed to two consecutive 4 min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P = 0.036), but not in preterm-born (-4 ± 27%, P = 0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P = 0.026) but not in preterm-born adults (-21 ± 107%, P = 0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P < 0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P = 0.012) and lower hypercapnic (P = 0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

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-1  min-1 ) 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-1  min-1 ). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO2 ), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O2 and CO2 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 F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ). 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 CO2 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.

The V˙O2max Legacy of Hill and Lupton (1923)-100 Years On.

PURPOSE: One hundred years ago, Hill and Lupton introduced the concept of maximal oxygen uptake (V˙O2max), which is regarded as "the principal progenitor of sports physiology." We provide a succinct overview of the evolvement of research on V˙O2max, from Hill and Lupton's initial findings to current debates on limiting factors for V˙O2max and the associated role of convective and diffusive components. Furthermore, we update the current use of V˙O2max in elite endurance sport and clinical settings. Practical Applications and Conclusions: V˙O2max is a healthy and active centenarian that remains a very important measure in elite endurance sports and additionally contributes as an important vital sign of cardiovascular function and fitness in clinical settings. Over the past 100 years, guidelines for the test protocols and exhaustion criteria, as well as the understanding of limiting factors for V˙O2max, have improved dramatically. Presently, possibilities of accurate and noninvasive determination of the convective versus diffusive components of V˙O2max by wearable sensors represent an important future application. V˙O2max is not only an indicator of cardiorespiratory function, fitness, and endurance performance but also represents an important biomarker of cardiovascular function and health to be included in routine assessment in clinical practice.

AltitudeOmics: effects of 16 days acclimatization to hypobaric hypoxia on muscle oxygen extraction during incremental exercise.

Acute altitude exposure lowers arterial oxygen content ([Formula: see text]) and cardiac output ([Formula: see text]) at peak exercise, whereas O2 extraction from blood to working muscles remains similar. Acclimatization normalizes [Formula: see text] but not peak [Formula: see text] nor peak oxygen consumption (V̇o2peak). To what extent acclimatization impacts muscle O2 extraction remains unresolved. Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O2Hb) and deoxyhemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O2 content ([Formula: see text]), [Formula: see text], and V̇o2. The HHb-V̇o2 slope was taken as a surrogate for muscle O2 extraction. During moderate-intensity exercise, HHb-V̇o2 slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared with SL (1.27 ± 0.12), indicating increased O2 extraction. However, the HHb/[Formula: see text] ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb-V̇o2 slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Increased muscle O2 extraction during submaximal exercise was associated with decreased [Formula: see text] in acute hypoxia. The significantly greater muscle O2 extraction during maximal exercise in chronic hypoxia is suggestive of an O2 reserve.NEW & NOTEWORTHY During incremental exercise muscle deoxyhemoglobin (HHb) and oxygen consumption (V̇o2) both increase linearly, and the slope of their relationship is an indirect index of local muscle O2 extraction. The latter was assessed at sea level, in acute and during chronic exposure to 5,260 m. The demonstrated presence of a muscle O2 extraction reserve during chronic exposure is coherent with previous studies indicating both limited muscle oxidative capacity and decrease in motor drive.

Hemoglobin Mass and Blood Volume in Swimming: A Comparison Between Highly Trained, Elite, and World-Class Swimmers.

PURPOSE: Total hemoglobin mass (tHbmass) and blood volume (BV) are important determinants of maximal oxygen uptake and endurance capacity. Higher-caliber endurance athletes usually possess higher tHbmass and BV values. This study aimed to compare tHbmass and BV among swimmers of diverse competitive calibers and distances. METHODS: Thirty swimmers (16 female and 14 male) participated in the study: 3 were tier 5, world class (869 [59] FINA points); 15 were tier 4, elite/international (853 [38] points); and 12 were tier 3, highly trained/national (808 [35] points). They specialized in competition distances ranging from 200 m to open-water 10 km. Between February 2019 and February 2020, all swimmers had their tHbmass and BV measured by carbon monoxide rebreathing 1 to 6 times and participated in multiple competitions and race events. RESULTS: Relative tHbmass and BV were not different (P > .05) between tiers among women or among men (pooled tHbmass values 14.5 [0.5], 12.5 [1.5], 12.6 [2.3] g/kg for tier 5, tier 4, and tier 3, respectively). No differences were observed in relative tHbmass (P = .215) and BV (P = .458) between pool and open-water swimmers or between 200-, 400-, and 1500-m specialists (P > .05). No significant correlations were found between the highest measured absolute or relative tHbmass and BV and the highest FINA points scored over the follow-up period (R = -.42-.17, P = .256-.833), irrespective of competition distance. CONCLUSION: tHbmass and BV values did not differ between swimmers of different calibers or among competition distances. Furthermore, these values did not correlate with FINA points, either in males or in females. The present results indicate that hematological characteristics may have a lesser impact on swimming performance than on land-based endurance sports.

End-tidal carbon dioxide tension is a reliable surrogate of arterial carbon dioxide tension across different oxygen, carbon dioxide and barometric pressures.

End-tidal CO2 tension provides an accurate estimation of P aCO2 in healthy awake individuals over an extensive range of CO2 pressures induced by 17 environmental conditions combining different O2, CO2 and barometric pressures https://bit.ly/3YuKPAY.

High-Intensity Interval Training, Performance, and Oxygen Uptake Kinetics in Highly Trained Traditional Rowers.

PURPOSE: Oxygen uptake kinetics (VO2kinetics) is a measure of an athlete's capacity to respond to variations in energy demands. Faster VO2kinetics is associated with better performance in endurance sports, but optimal training methods to improve VO2kinetics remain unclear. This study compared the effects of 2 high-intensity interval-training (HIIT) programs on traditional rowing performance and VO2kinetics. METHODS: Twelve highly trained rowers performed one of two 6-week HIIT protocols: either 3-minute repetitions at 90% (HIIT90; n = 5) of peak aerobic power (PAP) or 90-second repetitions at 100% (HIIT100; n = 7) of PAP. Before (PRE) and after (POST) the training intervention, they performed an incremental test to exhaustion to determine the individual lactate threshold, onset of blood lactate accumulation and PAP, and two 6-minute rest-to-exercise transitions to determine VO2kinetics. RESULTS: No significant changes (P > .05) were observed for rowing ergometer power output at individual lactate threshold (HIIT90 PRE 255 [12], POST 264 [13]; HIIT100 247 [24], 266 [28] W), onset of blood lactate accumulation (279 [12], 291 [16]; 269 [23], 284 [32] W), or PAP (359 [13], 381 [15]; 351 [21], 363 [29] W) or for any parameters of VO2kinetics. No differences were observed between HIIT interventions. CONCLUSION: The HIIT interventions did not induce significant performance or VO2kinetics improvements, although mean power output at individual lactate threshold, onset of blood lactate accumulation, and PAP increased by 5.7%, 5.0%, and 4.5%, respectively. This suggests that the exact intensity and duration of HIIT sessions performed in the same intensity domain may be of lesser importance than other well-established influential factors (eg, training volume progression, training intensity distribution, altitude training) to develop aerobic qualities in endurance athletes.

Both Hypoxia and Hypobaria Impair Baroreflex Sensitivity but through Different Mechanisms.

Baroreflex sensitivity (BRS) is a measure of cardiovagal baroreflex and is lower in normobaric and hypobaric hypoxia compared to normobaric normoxia. The aim of this study was to assess the effects of hypobaria on BRS in normoxia and hypoxia. Continuous blood pressure and ventilation were recorded in eighteen seated participants in normobaric normoxia (NNx), hypobaric normoxia (HNx), normobaric hypoxia (NHx) and hypobaric hypoxia (HHx). Barometric pressure was matched between NNx vs. NHx (723±4 mmHg) and HNx vs. HHx (406±4 vs. 403±5 mmHg). Inspired oxygen pressure (PiO2) was matched between NNx vs. HNx (141.2±0.8 vs. 141.5±1.5 mmHg) and NHx vs. HHx (75.7±0.4 vs. 74.3±1.0 mmHg). BRS was assessed using the sequence method. BRS significantly decreased in HNx, NHx and HHx compared to NNx. Heart rate, mean systolic and diastolic blood pressures did not differ between conditions. There was the specific effect of hypobaria on BRS in normoxia (BRS was lower in HNx than in NNx). The hypoxic and hypobaric effects do not add to each other resulting in comparable BRS decreases in HNx, NHx and HHx. BRS decrease under low barometric pressure requires future studies independently controlling O2 and CO2 to identify central and peripheral chemoreceptors' roles.

Physiological Responses to Exercise in Hypoxia in Preterm Adults: Convective and Diffusive Limitations in the O 2 Transport.

PURPOSE: Premature birth induces long-term sequelae on the cardiopulmonary system, leading to reduced exercise capacity. However, the mechanisms of this functional impairment during incremental exercise remain unclear. Also, a blunted hypoxic ventilatory response was found in preterm adults, suggesting an increased risk for adverse effects of hypoxia in this population. This study aimed to investigate the oxygen cascade during incremental exercise to exhaustion in both normoxia and hypobaric hypoxia in prematurely born adults with normal lung function and their term born counterparts. METHODS: Noninvasive measures of gas exchange, cardiac hemodynamics, and both muscle and cerebral oxygenation were continuously performed using metabolic cart, transthoracic impedance, and near-infrared spectroscopy, respectively, during an incremental exercise test to exhaustion performed at sea level and after 3 d of high-altitude exposure in healthy preterm ( n = 17; gestational age, 29 ± 1 wk; normal lung function) and term born ( n = 17) adults. RESULTS: At peak, power output, oxygen uptake, stroke volume indexed for body surface area, and cardiac output were lower in preterm compared with term born in normoxia ( P = 0.042, P = 0.027, P = 0.030, and P = 0.018, respectively) but not in hypoxia, whereas pulmonary ventilation, peripheral oxygen saturation, and muscle and cerebral oxygenation were similar between groups. These later parameters were modified by hypoxia ( P < 0.001). Hypoxia increased muscle oxygen extraction at submaximal and maximal intensity in term born ( P < 0.05) but not in preterm participants. Hypoxia decreased cerebral oxygen saturation in term born but not in preterm adults at rest and during exercise ( P < 0.05). Convective oxygen delivery was decreased by hypoxia in term born ( P < 0.001) but not preterm adults, whereas diffusive oxygen transport decreased similarly in both groups ( P < 0.001 and P < 0.001, respectively). CONCLUSIONS: These results suggest that exercise capacity in preterm is primarily reduced by impaired convective, rather than diffusive, oxygen transport. Moreover, healthy preterm adults may experience blunted hypoxia-induced impairments during maximal exercise compared with their term counterparts.

Daily cardiac autonomic responses during the Tour de France in a male professional cyclist.

Background: Heart rate variability (HRV) is a common means of monitoring responses to training, yet in professional cycling, one may question its usefulness, particularly during multi-day competitions such as Grand Tours. Objectives: This study aims to report and analyze HRV responses in a male professional cyclist over a season, including the Tour de France. Methods: A professional cyclist recorded resting and exercise inter-beat intervals during 5 months, comprising a training period with two altitude sojourns and two competition blocks, including the Tour de France. Resting recordings lasted 5 min in the supine position and were used for computation of mean heart rate (HR), root mean square of the successive differences (RMSSDs), and power in the low- and high-frequency bands (LF and HF, respectively). Training load quantification was based on recorded HR during exercise and expressed as training impulses (TRIMPSs). Results: LF (3,319 ± 2,819 vs. 1,097 ± 1,657 ms2), HF (3,590 ± 1858 vs. 1,267 ± 1,683 ms2), and RMSSD (96 ± 26 vs. 46 ± 30 ms) were higher and HR (47 ± 4 vs. 54 ± 2 bpm) was lower during the training period when compared to the two competition blocks. The coefficient of variation (CV) was significantly lower during the training period than during the two competition blocks for RMSSD (26 vs. 72%), LF (85 vs. 160%), and HF (58 vs. 141%). Discussion: The present study confirms that monitoring daily HRV responses during training periods is valuable in professional cycling, but questions its usefulness during the Tour de France. Moreover, the previous suggestion that CV in RMSSD would help to predict poor performance was not confirmed in a professional cyclist.

Saxagliptin: A potential doping agent? A randomized, double-blinded, placebo-controlled, and crossover pilot study in young active men.

Neuropeptide Ys (NPYs) contribute to sympathetic-adreno stimulation: NPY1-36 potentiates the effects of catecholamines (CATs), whereas NPY3-36 inhibits CAT release. We sought to investigate whether inhibiting dipeptidyl-peptidase-4 (DPP4), cleaving NPY1-36 into NPY3-36, leads to increased NPY1-36 potentiating effects and reduced NPY3-36 inhibitory effects on CATs, thereby improving endurance performance. Seven male participants (age 27 ± 3 years, BMI 23.1 ± 2.4 kg/m2 ) performed time-to-exhaustion cycling exercise at 95% of peak power output with either placebo, or saxagliptin, a DPP4 inhibitor. Oxygen consumption (V̇O2 ), heart rate variability, NPY1-36, NPY3-36, catecholamines, and lactate were measured at several time points before, during, and after exercise. With saxagliptin, DPP4 activity (12.7 ± 1.6 vs. 0.2 ± 0.3 U/L, p = 0.001; d = 10.7) was decreased at rest, while NPY3-36 (1.94 ± 0.88 vs. 0.73 ± 0.22 pm; p < 0.001; d = 2.04) decreased and NPY1-36 increased during exercise (2.64 ± 2.22 vs. 4.59 ± 2.98 pm; p < 0.01; d = 0.19). CATs were unchanged. Time-to-exhaustion was 32% higher with saxagliptin. The difference in time-to-exhaustion between placebo and saxagliptin was correlated with NPY1-36 differences (R = 0.78, p < 0.05). Peak V̇O2 and other cardio-respiratory values were not different, whereas peak NPY concentrations were higher with saxagliptin. DPP4 blockade improved performance, increased NPY1-36, and decreased NPY3-36 concentrations which may have potentiating effects on the influences of CATs. However, DPP4 is involved in many different actions, thus NPYs are one group of factors that may underly its performance-enhancing effects; further studies are required to determine the exact mechanisms.

Brain-muscle interplay during endurance self-paced exercise in normobaric and hypobaric hypoxia.

Purpose: Hypoxia is one major environmental factor, supposed to mediate central motor command as well as afferent feedbacks at rest and during exercise. By using a comparison of normobaric (NH) and hypobaric (HH) hypoxia with the same ambient pressure in oxygen, we examined the potential differences on the cerebrovascular and muscular regulation interplay during a self-paced aerobic exercise. Methods: Sixteen healthy subjects performed three cycling time-trials (250 kJ) in three conditions: HH, NH and normobaric normoxia (NN) after 24 h of exposure. Cerebral and muscular oxygenation were assessed by near-infrared spectroscopy, cerebral blood flow by Doppler ultrasound system. Gas exchanges, peripheral oxygen saturation, power output and associated pacing strategies were also continuously assessed. Results: The cerebral oxygen delivery was lower in hypoxia than in NN but decreased similarly in both hypoxic conditions. Overall performance and pacing were significantly more down-regulated in HH versus NH, in conjunction with more impaired systemic (e.g. saturation and cerebral blood flow) and prefrontal cortex oxygenation during exercise. Conclusions: The difference in pacing was likely the consequence of a complex interplay between systemic alterations and cerebral oxygenation observed in HH compared to NH, aiming to maintain an equivalent cerebral oxygen delivery despite higher adaptive cost (lower absolute power output for the same relative exercise intensity) in HH compared to NH.

RMSSD Is More Sensitive to Artifacts Than Frequency-Domain Parameters: Implication in Athletes' Monitoring.

Easy-to-use and accurate heart rate variability (HRV) assessments are essential in athletes' follow-up, but artifacts may lead to erroneous analysis. Artifact detection and correction are the purpose of extensive literature and implemented in dedicated analysis programs. However, the effects of number and/or magnitude of artifacts on various time- or frequency-domain parameters remain unclear. The purpose of this study was to assess the effects of artifacts on HRV parameters. Root mean square of the successive differences (RMSSD), standard deviation of the normal to normal inter beat intervals (SDNN), power in the low- (LF) and high-frequency band (HF) were computed from two 4-min RR recordings in 178 participants in both supine and standing positions, respectively. RRs were modified by (1) randomly adding or subtracting 10, 30, 50 or 100 ms to the successive RRs; (2) a single artifact was manually inserted; (3) artifacts were automatically corrected from signal naturally containing artifacts. Finally, RR recordings were analyzed before and after automatic detection-correction of artifacts. Modifying each RR by 10, 30, 50 and 100 ms randomly did not significantly change HRV parameters (range -6%, +6%, supine). In contrast, by adding a single artifact, RMSSD increased by 413% and 269%, SDNN by 54% and 47% in supine and standing positions, respectively. LF and HF changed only between -3% and +8% (supine and standing) in the artifact condition. When more than 0.9% of the signal contained artifacts, RMSSD was significantly biased, whilst when more than 1.4% of the signal contained artifacts LF and HF were significantly biased. RMSSD and SDNN were more sensitive to a single artifact than LF and HF. This indicates that, when using RMSSD only, a single artifact may induce erroneous interpretation of HRV. Therefore, we recommend using both time- and frequency-domain parameters to minimize the errors in the diagnoses of health status or fatigue in athletes.

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 (V̇O2), 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.

Effects of Pre-Term Birth on the Cardio-Respiratory Responses to Hypoxic Exercise in Children.

Pre-term birth is associated with numerous cardio-respiratory sequelae in children. Whether these impairments impact the responses to exercise in normoxia or hypoxia remains to be established. Fourteen prematurely-born (PREM) (Mean ± SD; gestational age 29 ± 2 weeks; age 9.5 ± 0.3 years), and 15 full-term children (CONT) (gestational age 39 ± 1 weeks; age 9.7 ± 0.9 years), underwent incremental exercise tests to exhaustion in normoxia (FiO2 = 20.9%) and normobaric hypoxia (FiO2 = 13.2%) on a cycle ergometer. Cardio-respiratory variables were measured throughout. Peak power output was higher in normoxia than hypoxia (103 ± 17 vs. 77 ± 18 W; p < 0.001), with no difference between CONT and PREM (94 ± 23 vs. 86 ± 19 W; p = 0.154). VO2peak was higher in normoxia than hypoxia in CONT (50.8 ± 7.2 vs. 43.8 ± 9.9 mL·kg-1·min-1; p < 0.001) but not in PREM (48.1 ± 7.5 vs. 45.0 ± 6.8 mL·kg-1·min-1; p = 0.137; interaction p = 0.044). Higher peak heart rate (187 ± 11 vs. 180 ± 10 bpm; p = 0.005) and lower stroke volume (72 ± 13 vs. 77 ± 14 mL; p = 0.004) were observed in normoxia versus hypoxia in CONT, with no such differences in PREM (p = 0.218 and >0.999, respectively). In conclusion, premature birth does not appear to exacerbate the negative effect of hypoxia on exercise capacity in children. Further research is warranted to identify whether prematurity elicits a protective effect, and to clarify the potential underlying mechanisms.