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Competing Interests: Competing interests: None declared.

Citherlet, Tom, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, and Grégoire P Millet. Impact of the menstrual cycle (MC) on the cardiovascular and ventilatory responses during exercise in normoxia and hypoxia. High Alt Med Biol. 00:00-00, 2024. Introduction: Ovarian hormones influence several physiological functions in women. This study investigated how the hormonal variations across the menstrual cycle (MC) impact cardiovascular and ventilatory responses during rest and moderate exercise in normobaric hypoxia. Methods: Thirteen eumenorrheic women were tested during the early follicular (Fol1), late follicular (Fol2), and mid-luteal (Lut3) phases with measurement of hormonal levels. Heart rate (HR) variability, blood pressure, and baroreflex sensitivity (BRS) were evaluated at rest in normoxia. Ventilation (VE), peripheral oxygen saturation, and HR were monitored at rest and during moderate-intensity cycling exercise in hypoxia (F i O 2 = 14%). Results: Despite expected hormone level variations, no significant changes were observed across the MC in HR variability (root mean square of successive differences; 64 (95% confidence interval [47, 81]) at Fol1, 54 [42, 66] at Fol2, 60 [44, 77] ms at Lut3), blood pressure (mean blood pressure; 85 [79, 90]), 87 [81, 93]), 84 [77, 92] mmHg), BRS (26 [17, 36], 28 [20, 35], 23 [17, 29] ms/mmHg), VE (rest: 8.9 [7.9, 9.8], 9.5 [9.0, 9.9], 9.0 [8.1, 9.9]; exercise: 53 [41, 66], 51.1 [36.4, 65.7], 54.4 [34.0, 74.8] l/min), peripheral oxygen saturation (rest: 89.8 [87.4, 92.1], 91.9 [88.7, 95.0], 90.2 [87.8, 92.6]; exercise: 80.5 [77.4, 83.5], 84.4 [80.4, 88.3], 81.9 [78.3, 85.4] %) HR (rest: 69.7 [60.2, 79.1], 70.8 [63.2, 78.3], 70.5 [64.0, 77.0]; exercise: 148 [136, 160], 146 [132, 161], 146 [132, 160] bpm), and cycling efficiency (0.17 [0.16, 0.18], 0.17 [0.13, 0.21], 0.16 [0.15, 0.18] %) (all p > 0.05). Discussion: From a practical point of view, there is no strong evidence of any usefulness of monitoring hormonal variations and the MC phases for women exercising in hypoxia.

Preterm birth elicits long-lasting physiological effects in various organ systems, potentially modulating exercise and environmental stress responses. To establish whether prematurely-born adults respond uniquely during early high-altitude acclimatization at rest and during exercise, 17 healthy adults born preterm (gestational age < 32 wk) and 17 term-born, age- and aerobic-capacity-matched, control participants completed a three-day high-altitude sojourn (3,375 m). Oxygen uptake, pulmonary ventilation, and hemodynamic responses, as well as pulse oxygen saturation, brain tissue saturation index (TSI), and skeletal muscle TSI, were measured daily at rest and during moderate-intensity steady-state exercise bouts. In general, the prematurely-born group displayed comparable acclimatization responses at rest, with similar ventilation and cardiac output observed between groups throughout. Resting brain TSI was, however, higher in the preterm group upon arrival at high altitude (72 ± 7% vs. 68 ± 3%; d = 1.20). Absolute exercising oxygen uptake was lower in the preterm participants ( P = 0.047), with this group displaying lower exercising cardiac output underpinned by reduced stroke volume (both P = 0.035). Nevertheless, exercising minute ventilation (V̇e) did not differ between groups ( P = 0.237) while brain TSI (70 ± 6% vs. 66 ± 3%; d = 1.35) and pulse oxygen saturation (85 ± 3% vs. 82 ± 5%; d = 1.52) were higher with prematurity upon arrival to high altitude. These findings suggest that healthy prematurely-born adults exhibit comparable early acclimatization patterns to their term-born counterparts and better maintain cerebral oxygenation at rest. Together, these data suggest that prematurely-born adults should not be discouraged from high-altitude sojourns involving physical activity. NEW & NOTEWORTHY The acclimatization pattern across three days at 3,375 m, at rest and during moderate-intensity exercise, was similar between healthy adults born prematurely and their term-born counterparts. Preterm adults free from respiratory complications were found to better maintain brain tissue and capillary oxygen saturation at high altitudes, whereas the term-born group experienced larger altitude-induced reductions. Despite apparent cardiac limitations, preterm individuals tolerated exercise similarly to their term-born peers. These findings underscore the notion that preterm birth per se does not predispose healthy adults to decreased altitude tolerance during exercise.

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, because of 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 (V̇ E ) ( P < 0.001), larger ΔVO 2max ( P = 0.019), and lower hypoxia-related V̇ E 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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

The present study investigated the maintenance/repeatability of expiratory flow limitation (EFL) between normoxia and hypoxia. Fifty-one healthy active individuals (27 men and 24 women) performed a lung function test and a maximal incremental cycling test in both normoxia and hypoxia (inspired oxygen fraction = 0.14) on two separate visits. During exercise in normoxia, 28 participants exhibited EFL (55 %). In hypoxia, another cohort of 28 participants exhibited EFL. The two groups only partly overlapped. Individuals with EFL only in normoxia reported lower maximal ventilation values in hypoxia than in normoxia (n=5; -13.5 ± 7.8 %) compared to their counterparts with EFL only in hypoxia (n=5; +6.7 ± 6.3 %) or without EFL (n=18; +5.1 ± 10.3 %) (p=0.004 and p<0.001, respectively). EFL development may be induced by different mechanisms in hypoxia vs. normoxia since the individuals who exhibited flow limitation were not the same between the two environmental conditions. This change seems influenced by the magnitude of the maximal ventilation change., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Microvascular impairments are typical of several cardiovascular diseases. Near-infrared spectroscopy (NIRS) combined with a vascular occlusion test provides non-invasive insights into microvascular responses by monitoring skeletal muscle oxygenation changes during reactive hyperaemia. Despite increasing interest in the effects of sex and ageing on microvascular responses, evidence remains inconsistent. Therefore, the present study aimed to investigate the effects of sex and age on microvascular responsiveness. Twenty-seven participants (seven young men and seven young women; seven older men and six older women; aged 26 ± 1, 26 ± 4, 67 ± 3 and 69 ± 4 years, respectively) completed a vascular occlusion test consisting of 5 min of arterial occlusion followed by 5 min reperfusion. Oxygenation changes in the vastus lateralis were monitored by near-infrared spectroscopy. The findings revealed that both women (referring to young and older women) and older participants (referring to both men and women) exhibited lower microvascular responsiveness. Notably, both women and older participants demonstrated reduced desaturation (-38% and -59%, respectively) and reperfusion rates (-24% and -40%, respectively) along with a narrower range of tissue oxygenation (-39% and -39%, respectively) and higher minimal tissue oxygenation levels (+34% and +21%, respectively). Women additionally displayed higher values in resting (+12%) and time-to-peak (+15%) tissue oxygenation levels. In conclusion, this study confirmed decreased microvascular responses in women and older individuals. These results emphasize the importance of considering sex and age when studying microvascular responses. Further research is needed to uncover the underlying mechanisms and clinical relevance of these findings, enabling the development of tailored strategies for preserving vascular health in diverse populations., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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 + CO 2 ), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO 2 ), and hypobaric hypoxia with end-tidal CO 2 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 CO 2 in healthy prematurely born adults., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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% CO 2 -97% O 2 ; 6% CO 2 -94% O 2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO 2 , 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 CO 2 , 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) CO 2 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., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

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.

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. -15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. -13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm., (© 2023. The Author(s).)

End-tidal CO 2 tension provides an accurate estimation of P aCO 2 in healthy awake individuals over an extensive range of CO 2 pressures induced by 17 environmental conditions combining different O 2 , CO 2 and barometric pressures https://bit.ly/3YuKPAY., Competing Interests: Conflict of interest: No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright ©The authors 2023.)

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., (Copyright © 2022 by the American College of Sports Medicine.)

The pre-term birth survival rate has increased considerably in recent decades, and research investigating the long-term effects of premature birth is growing. Moreover, altitude sojourns are increasing in popularity and are often accompanied by various levels of physical activity. Individuals born pre-term appear to exhibit altered acute ventilatory responses to hypoxia, potentially predisposing them to high-altitude illness. These impairments are likely due to the use of perinatal hyperoxia stunting the maturation of carotid body chemoreceptors, but may also be attributed to limited lung diffusion capacity and/or gas exchange inefficiency. Aerobic exercise capacity also appears to be reduced in this population. This may relate to the aforementioned respiratory impairments, or could be due to physiological limitations in pulmonary blood flow or at the exercising muscle (e.g. mitochondrial efficiency). However, surprisingly, the debilitative effects of exercise when performed at altitude do not seem to be exacerbated by premature birth. In fact, it is reasonable to speculate that pre-term birth could protect against the consequences of exercise combined with hypoxia. The mechanisms that underlie this assertion might relate to differences in oxidative stress responses or in cardiopulmonary morphology in pre-term individuals, compared to their full-term counterparts. Further research is required to elucidate the independent effects of neonatal treatment, sex differences and chronic lung disease, and to establish causality in some of the proposed mechanisms that could underlie the differences discussed throughout this review. A more in-depth understanding of the acclimatisation responses to chronic altitude exposures would also help to inform appropriate interventions in this clinical population., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aerobic exercise prescription is often set at specific heart rate (HR) values. Previous studies demonstrated that during exercise carried out at a HR slightly above that corresponding to the gas exchange threshold (GET), work rate (WR) has to decrease in order to maintain HR constant. We hypothesized a greater WR decrease at a fixed HR after simulated microgravity/inactivity (bed rest, BR). Ten male volunteers (23 ± 5 yr) were tested before (PRE) and after (POST) a 10-day horizontal BR and performed on a cycle ergometer 1 ) incremental exercise; b ) 15-min HR CLAMPED exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to that at 120% of GET determined in PRE; 3 ) two moderate-intensity constant WR (MOD) exercises. Breath-by-breath O 2 uptake (V̇o 2 ), HR, and other variables were determined. After BR, peak V̇o 2 (V̇o 2peak ) and GET significantly decreased, by ∼10%. During HR CLAMPED (145 ± 11 beats·min -1 ), the decrease in WR needed to maintain a constant HR was greater in POST versus PRE (-39 ± 10% vs. -29 ± 14%, P < 0.01). In six subjects the decreased WR switched from the heavy- to the moderate-intensity domain. The decrease in WR during HR CLAMPED , in PRE versus POST, was significantly correlated with the V̇o 2peak decrease ( R 2 = 0.52; P = 0.02). A greater amplitude of the slow component of the HR kinetics was observed during MOD following BR. Exercise at a fixed HR is not associated with a specific WR or WR domain; the problem, affecting exercise evaluation and prescription, is greater after BR. The WR decrease during HR CLAMPED is a biomarker of exercise intolerance after BR. NEW & NOTEWORTHY During a 15-min exercise carried out at a heart rate (HR) slightly above that corresponding to the gas exchange threshold, to keep HR constant work rate significantly decreased; the decrease was more pronounced after a 10-day horizontal bed rest. The work rate decrease at a fixed HR can be considered a systemic biomarker of exercise intolerance during microgravity/inactivity and could also be easily and reliably determined during spaceflights or in patients.

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 (FiO 2 = 20.9%) and normobaric hypoxia (FiO 2 = 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). VO 2 peak 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.

Manferdelli, Giorgio, Benjamin J. Narang, Mathias Poussel, Damjan Osredkar, Grégoire P. Millet, and Tadej Debevec. Long-term effects of prematurity on resting ventilatory response to hypercapnia. High Alt Med Biol . 22:420-425, 2021. Background: This study investigated the resting ventilatory response to hypercapnia in prematurely born adults. Materials and Methods: Seventeen preterm and fourteen full-term adults were exposed to normoxic hypercapnia (two 5-minute periods at 3% and 6% carbon dioxide [CO 2 ] interspersed by 5-minute in normoxia). Pulmonary ventilation ([Formula: see text]) and end-tidal partial pressure of CO 2 (Petco 2 ) were measured continuously. Results: No difference in lung function was observed between preterm and full-term adults. Petco 2 was lower in preterm than in full-term adults ( p  < 0.05) during normoxia. During exposure to 3% CO 2 , both [Formula: see text] and Petco 2 increased in a similar way in preterm and full-term adults. However, at the end of the 6% CO 2 period, there was a significantly higher [Formula: see text] in preterm compared with full-term adults (30.2 ± 7.5 vs. 23.7 ± 4.5 L/min, p  < 0.0001), whereas no difference was observed for Petco 2 (46.9 ± 2.1 vs. 50.6 ± 2.1 L/min, p  = 0.99). Breath frequency was higher in preterm than in full-term adults (17.9 ± 4.0 vs. 12.8 ± 3.5 b/min, p  < 0.01) during 6% CO 2 exposure. Conclusions: Although data suggest that prematurity results in resting hypocapnia, the exact underlying mechanisms remain to be elucidated. Moreover, preterm adults seem to have increased chemosensitivity to hypercapnia.

In order to identify peripheral biomarkers of impaired oxidative metabolism during exercise following a 10-day bed rest, 10 males performed an incremental exercise (to determine peak pulmonary V̇O 2 (V̇O 2 p)) and moderate-intensity exercises, before (PRE) and after (POST) bed rest. Blood flow response was evaluated in the common femoral artery by Eco-Doppler during 1 min of passive leg movements (PLM). The intramuscular matching between O 2 delivery and O 2 utilization was evaluated by near-infrared spectroscopy (NIRS). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in isolated muscle fibres, and in vivo by NIRS by the evaluation of skeletal muscle V̇O 2 (V̇O 2 m) recovery kinetics. Resting V̇O 2 m was estimated by NIRS. Peak V̇O 2 p was lower in POST vs. PRE. The area under the blood flow vs. time curve during PLM was smaller (P = 0.03) in POST (274 ± 233 mL) vs. PRE (427 ± 291). An increased (P = 0.03) overshoot of muscle deoxygenation during a metabolic transition was identified in POST. Skeletal muscle citrate synthase activity was not different (P = 0.11) in POST (131 ± 16 nmol min -1  mg -1 ) vs. PRE (138 ± 19). Maximal ADP-stimulated mitochondrial respiration (66 ± 18 pmol s -1  mg -1 (POST) vs. 72 ± 14 (PRE), P = 0.41) was not affected by bed rest. Apparent K m for ADP sensitivity of mitochondrial respiration was reduced in POST vs. PRE (P = 0.04). The V̇O 2 m recovery time constant was not different (P = 0.79) in POST (22 ± 6 s) vs. PRE (22 ± 6). Resting V̇O 2 m was reduced by 25% in POST vs. PRE (P = 0.006). Microvascular-endothelial function was impaired following a 10-day bed rest, whereas mitochondrial mass and function (both in vivo and ex vivo) were unaffected or slightly enhanced. KEY POINTS: Ten days of horizontal bed rest impaired in vivo oxidative function during exercise. Microvascular impairments were identified by different methods. Mitochondrial mass and mitochondrial function (evaluated both in vivo and ex vivo) were unchanged or even improved (i.e. enhanced mitochondrial sensitivity to submaximal [ADP]). Resting muscle oxygen uptake was significantly lower following bed rest, suggesting that muscle catabolic processes induced by bed rest/inactivity are less energy-consuming than anabolic ones., (© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the central question of this study? The role of the cerebral haemodynamic response to either normobaric or hypobaric hypoxia in people susceptible to acute mountain sickness (AMS) is still under debate. Prefrontal cortex near-infrared spectroscopy-derived parameters were monitored in normobaric hypoxia at rest and during moderate-intensity exercise in AMS-prone and non-AMS individuals. What is the main finding and its importance? The AMS-prone individuals did not increase microvascular blood volume and showed lower prefrontal cerebral oxygenation in normobaric hypoxia both at rest and during exercise compared with non-AMS subjects, suggesting that these changes might underpin later development of AMS at altitude., Abstract: The aim of this study was to evaluate changes in prefrontal cerebral oxygenation and microvascular blood volume during exercise in normobaric hypoxia and to investigate possible associations with the occurrence of acute mountain sickness (AMS) at altitude. Twenty-two healthy individuals (age, 26 ± 4 years; peak oxygen uptake, 42 ± 4 ml kg -1  min -1 ) were tested in two different conditions: normoxia (NORM) and normobaric hypoxia (fraction of inspired O 2  = 0.13; HYPO). Data were collected at rest and during submaximal constant-speed exercise. The peripheral oxyhaemoglobin saturation was measured by finger pulse oximeter. Changes in prefrontal cerebral oxygenation (ΔHbO 2 ), deoxygenation (ΔHHb) and microvascular blood volume (ΔHb tot ) were obtained by near-infrared spectroscopy. Within 2 weeks after laboratory testing, subjects rapidly ascended to 3647 m a.s.l., and AMS was evaluated using the Lake Louise scale. Eight subjects were AMS + , whereas 14 were AMS - . During NORM, near-infrared spectroscopy variables did not change from baseline values both at rest and during exercise, with similar results in AMS + and AMS - subjects. During HYPO, ΔHHb increased to a similar extent in both groups, both at rest and during exercise. The ΔHbO 2 was significantly less in AMS + compared with AMS - subjects, both at rest [-3.23 ± 5.90 versus 1.44 ± 2.14 μm, P = 0.04, effect size (ES) = 1.1, respectively] and during exercise (-6.56 ± 5.51 versus 0.37 ± 4.36 μm, P < 0.01, ES = 1.2, respectively). Total haemoglobin did not change from baseline, both at rest (-1.67 ± 9.53 μm) and during exercise (-0.96 ± 9.12 μm) in AMS + subjects, which was significantly different from the AMS - group (5.49 ± 3.99 μm, P = 0.03, ES = 1.0 and 8.17 ± 7.34 μm, P = 0.02, ES = 1.0, respectively). Individuals prone to AMS seem to be unable to increase microvascular blood volume and to maintain oxygenation at the cerebral level during exercise in acute normobaric hypoxia, suggesting that these changes might underpin later development of AMS., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

In the context of the fourth revolution in healthcare technologies, leveraging monitoring and personalization across different domains becomes a key factor for providing useful services to maintain and promote well-being. This is even more crucial for older people, with aging being a complex multi-dimensional and multi-factorial process which can lead to frailty. The NESTORE project was recently funded by the EU Commission with the aim of supporting healthy older people to sustain their well-being and capacity to live independently. It is based on a multi-dimensional model of the healthy aging process that covers physical activity, nutrition, cognition, and social activity. NESTORE is based on the paradigm of the human-in-the-loop cyber-physical system that, exploiting the availability of Internet of Things technologies combined with analytics in the cloud, provides a virtual coaching system to support healthy aging. This work describes the design of the NESTORE methodology and its IoT architecture. We first model the end-user under several domains, then we present the NESTORE system that, analyzing relevant key-markers, provides coaching activities and personalized feedback to the user. Finally, we describe the validation strategy to assess the effectiveness of NESTORE as a coaching platform for healthy aging., (Copyright © 2020 Palumbo, Crivello, Furfari, Girolami, Mastropietro, Manferdelli, Röcke, Guye, Salvá Casanovas, Caon, Carrino, Abou Khaled, Mugellini, Denna, Mauri, Ward, Subías-Beltrán, Orte, Candea, Candea and Rizzo.)

This study aimed to compare selected hormonal responses to a single session of high intensity interval training performed with an increased fraction of inspired oxygen (hyperoxia) and under normoxic conditions. Twelve recreationally trained men (age 24 ± 3 years) performed two sessions of high intensity interval training on a cycle ergometer, in randomized order with hyperoxia (4 L·min -1 with a flowrate of 94% O 2 ) and normoxia. Each session consisted of 5 intervals of 3 minutes at 85% of the maximal power output, interspersed by 2 min at 40% of the maximal power output. Serum cortisol, prolactin and vascular endothelial growth factor (VEGF) were assessed both before and immediately after each high intensity interval training session. Statistically significant differences in cortisol were found between hyperoxic and normoxic conditions (p = 0.011), with a significant increase in hyperoxia (61.4 ± 73.2%, p = 0.013, ES = -1.03), but not in normoxia (-1.3 ± 33.5%, p > 0.05, ES = 0.1). Prolactin increased similarly in both hyperoxia (118.1 ± 145.1%, p = 0.019, ES = -0.99) and normoxia (62.14 ± 75.43%, p = 0.005, ES = -0.5). VEGF was not statistically altered in either of the conditions. Our findings indicate that a single session of high intensity interval training in low-dose hyperoxia significantly increased cortisol concentrations in recreationally trained individuals compared to normoxia, while the difference was smaller in prolactin and diminished in VEGF concentrations., (© 2020 Giorgio Manferdelli, Nils Freitag, Kenji Doma, Anthony C Hackney, Hans-Georg Predel, Wilhelm Bloch, Moritz Schumann, published by Sciendo.)

Recent technological developments provide easy access to use an artificial oxygen supply (hyperoxia) during exercise training. The aim of this study was to assess the efficacy of a commercially available oxygen compressor inducing low-dose hyperoxia, on limiting factors of endurance performance. Thirteen active men (age 24 ± 3 years) performed a high-intensity interval exercise (HIIE) session (5 × 3 min at 80% of W max , separated by 2 min at 40% W max ) on a cycle ergometer, both in hyperoxia (4 L∙min -1 , 94% O 2 , HYP) or ambient conditions (21% O 2 , NORM) in randomized order. The primary outcome was defined as red blood cell deformability (RBC-D), while our secondary interest included changes in muscle oxygenation. RBC-D was expressed by the ratio of shear stress at half-maximal deformation (SS 1 / 2 ) and maximal deformability (EI max ) and muscle oxygenation of the rectus femoris muscle was assessed by near-infrared spectroscopy. No statistically significant changes occurred in SS 1 / 2 and EI max in either condition. The ratio of SS 1 / 2 to EI max statistically decreased in NORM ( p < 0.01; Δ: -0.10; 95%CI: -0.22, 0.02) but not HYP ( p > 0.05; Δ: -0.16; 95%CI: -0.23, -0.08). Muscle oxygenation remained unchanged. This study showed that low-dose hyperoxia during HIIE using a commercially available device with a flow rate of only 4 L·min -1 may not be sufficient to induce acute ergogenic effects compared to normoxic conditions.

Introduction: Cutting-edge technologies and the rapid urbanization have led to several advantages for mankind and society. However such benefits have been accompanied with the alarming diffusion of sedentary lifestyle disorders, metabolic diseases, major depression and socialization problems, affecting global economy dramatically. The pandemic expansion of chronic diseases is associated with physical inactivity. During the last decade, numerous cities and organizations worldwide have started to adopt strategies aimed at improving outdoor physical activity levels in city residents., Evidence Acquisition: A systematic review focusing on the effects of regular outdoor sports and physical activities across all ages was conducted through multiple databases, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards., Evidence Synthesis: Performing outdoor sports and physical activities may bear social, psychological and physiological benefits. Preventive effects are similarly documented in youth and seniors towards several morbid conditions: vitamin D deficiency, multiple sclerosis, osteoporosis and myopia., Conclusions: Giving the beneficial effects of outdoor sports and physical activities, promotion strategies should be strongly advocated and developed nationally and globally. Likewise, dedicated research areas should inspire guidelines for the promotion of various outdoor activities - a good practice for the social scenario and the healthcare system.