Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance.

The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.

Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

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.

The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.

Age and sex differences in microvascular responses during reactive hyperaemia.

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.

Constant low-to-moderate mechanical asymmetries during 800-m track running.

Introduction: Modifications in asymmetry in response to self-paced efforts have not been thoroughly documented, particularly regarding horizontally-derived ground reaction force variables. We determined the magnitude and range of gait asymmetries during 800 m track running. Methods: Eighteen physical education students completed an 800 m self-paced run on a 200 m indoor track. During the run, vertical and horizontal ground reaction forces were measured at a sampling frequency of 500 Hz using a 5 m-long force platform system, with data collected once per lap. The following mechanical variables were determined for two consecutive steps: contact time and duration of braking/push-off phases along with vertical/braking/push-off peak forces and impulses. The group mean asymmetry scores were evaluated using the "symmetry angle" (SA) formula, where scores of 0% and 100% correspond to perfect symmetry and perfect asymmetry, respectively. Results: There was no influence of distance interval on SA scores for any of the nine biomechanical variables (P ≥ 0.095). The SA scores were ∼1%-2% for contact time (1.3 ± 0.5%), peak vertical forces (1.8 ± 0.9%), and vertical impulse (1.7 ± 1.0%). The SA scores were ∼3%-8% for duration of braking (3.6 ± 1.1%) and push-off (3.2 ± 1.4%) phases, peak braking (5.0 ± 2.1%) and push-off (6.9 ± 3.1%) forces as well as braking (7.6 ± 2.3%) and push-off (7.7 ± 3.3%) impulses. The running velocity progressively decreased at 300 m and 500 m compared to that at 100 m but levelled off at 700 m (P < 0.001). Discussion: There were no modifications in gait asymmetries, as measured at 200-m distance intervals during 800-m track running in physical education students. The 800 m self-paced run did not impose greater mechanical constraints on one side of the body. Experimental procedures for characterizing the gait pattern during 800 m track running could be simplified by collecting leg mechanical data from only one side.

Hypoxia Sensing and Responses in Parkinson's Disease.

Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential.

Effects of Hypoxia Severity on Muscle Oxygenation Kinetics Using Statistical Parametric Mapping During Repeated Treadmill Sprints.

PURPOSE: We examined the effects of increasing hypoxia severity on oxygenation kinetics in the vastus lateralis muscle during repeated treadmill sprints, using statistical parametric mapping (SPM). METHODS: Ten physically active males completed 8 sprints of 5 seconds each (recovery = 25 s) on a motorized sprint treadmill in normoxia (sea level; inspired oxygen fraction = 0.21), moderate hypoxia (inspired oxygen fraction = 0.17), and severe hypoxia (SH; inspired oxygen fraction = 0.13). Continuous assessment of tissue saturation index (TSI) in the vastus lateralis muscle was conducted using near-infrared spectroscopy. Subsequently, TSI data were averaged for the sprint-recovery cycle of all sprints and compared between conditions. RESULTS: The SPM analysis revealed no discernible difference in TSI signal amplitude between conditions during the actual 5-second sprint phase. However, during the latter portion of the 25-second recovery phase, TSI values were lower in SH compared with both sea level (from 22 to 30 s; P = .003) and moderate hypoxia (from 16 to 30 s; P = .001). The mean distance covered at sea level (22.9 [1.0] m) was greater than for both moderate hypoxia (22.5 [1.2] m; P = .045) and SH (22.3 [1.4] m; P = .043). CONCLUSIONS: The application of SPM demonstrated that only SH reduced muscle oxygenation levels during the late portion of the passive (recovery) phase and not the active (sprint) phase during repeated treadmill sprints. These findings underscore the usefulness of SPM for assessing muscle oxygenation differences due to hypoxic exposure and the importance of the duration of the between-sprints recovery period.

Acute Responses to Repeated-Sprint Training in Hypoxia Combined With Whole-Body Cryotherapy: A Preliminary Study.

PURPOSE: This study aimed to investigate acute psychophysiological responses to repeated-sprint training in hypoxia (RSH) combined with whole-body cryotherapy (WBC). METHOD: Sixteen trained cyclists performed 3 sessions in randomized order: RSH, WBC-RSH (WBC pre-RSH), and RSH-WBC (WBC post-RSH). RSH consisted of 3 sets of 5 × 10-second sprints with 20-second recovery at a simulated altitude of 3000 m. Power output, muscle oxygenation (tissue saturation index), heart-rate variability, and recovery perception were analyzed. Sleep quality was assessed on the nights following test sessions and compared with a control night using nocturnal ActiGraphy and heart-rate variability. RESULTS: Power output did not differ between the conditions (P = .27), while the decrease in tissue saturation index was reduced for WBC-RSH compared to RSH-WBC in the last set. In both conditions with WBC, the recovery perception was higher compared to RSH (WBC-RSH: +15.4%, and RSH-WBC: +21.9%, P < .05). The number of movements during the RSH-WBC night was significantly lower than for the control night (-18.7%, P < .01) and WBC-RSH (-14.9%, P < .05). RSH led to a higher root mean square of the successive differences of R-R intervals and high-frequency band during the first hour of sleep compared to the control night (P < .05) and RSH-WBC (P < .01). CONCLUSIONS: Inclusion of WBC in an RSH session did not modify the power output but could improve prolonged performance in hypoxia by maintaining muscle oxygenation. A single RSH session did not deteriorate sleep quality. WBC, particularly when performed after RSH, positively influenced recovery perception and sleep.

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.

Hypoxic peripheral chemoreflex stimulation-dependent cardiorespiratory coupling is decreased in swimmer athletes.

Swimmer athletes showed a decreased ventilatory response and reduced sympathetic activation during peripheral hypoxic chemoreflex stimulation. Based on these observations, we hypothesized that swimmers develop a diminished cardiorespiratory coupling due to their decreased hypoxic peripheral response. To resolve this hypothesis, we conducted a study using coherence time-varying analysis to assess the cardiorespiratory coupling in swimmer athletes. We recruited 12 trained swimmers and 12 control subjects for our research. We employed wavelet time-varying spectral coherence analysis to examine the relationship between the respiratory frequency (Rf ) and the heart rate (HR) time series during normoxia and acute chemoreflex activation induced by five consecutive inhalations of 100% N2 . Comparing swimmers to control subjects, we observed a significant reduction in the hypoxic ventilatory responses to N2 in swimmers (0.012 ± 0.001 vs. 0.015 ± 0.001 ΔVE /ΔVO2 , and 0.365 ± 0.266 vs. 1.430 ± 0.961 ΔVE /ΔVCO2 /ΔSpO2 , both p < 0.001, swimmers vs. control, respectively). Furthermore, the coherence at the LF cutoff during hypoxia was significantly lower in swimmers compared to control subjects (20.118 ± 3.502 vs. 24.935 ± 3.832 area under curve [AUC], p < 0.012, respectively). Our findings strongly indicate that due to their diminished chemoreflex control, swimmers exhibited a substantial decrease in cardiorespiratory coupling during hypoxic stimulation.

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.

Exercise and gait/movement analyses in treatment and diagnosis of Parkinson's Disease.

Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait, balance and postural patterns at advanced stages of the disease. Besides pharmacological and surgical therapies, physical exercise represents an important strategy for the management of these advanced impairments. Traditionally, diagnosis and classification of such abnormalities have relied on partially subjective evaluations performed by neurologists during short and temporally scattered hospital appointments. Emerging sports medical methods, including wearable sensor-based movement assessment and computational-statistical analysis, are paving the way for more objective and systematic diagnoses in everyday life conditions. These approaches hold promise to facilitate customizing clinical trials to specific PD groups, as well as personalizing neuromodulation therapies and exercise prescriptions for each individual, remotely and regularly, according to disease progression or specific motor symptoms. We aim to summarize exercise benefits for PD with a specific emphasis on gait and balance deficits, and to provide an overview of recent advances in movement analysis approaches, notably from the sports science community, with value for diagnosis and prognosis. Although such techniques are becoming increasingly available, their standardization and optimization for clinical purposes is critically missing, especially in their translation to complex neurodegenerative disorders such as PD. We highlight the importance of integrating state-of-the-art gait and movement analysis approaches, in combination with other motor, electrophysiological or neural biomarkers, to improve the understanding of the diversity of PD phenotypes, their response to therapies and the dynamics of their disease progression.

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.

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.

The link between impaired oxygen supply and cognitive decline in peripheral artery disease.

Although peripheral artery disease (PAD) primarily affects large arteries outside the brain, PAD is also associated with elevated cerebral vulnerabilities, including greater risks for brain injury (such as stroke), cognitive decline and dementia. In the present review, we aim to evaluate recent literature and extract information on potential mechanisms linking PAD and consequences on the brain. Furthermore, we suggest novel therapeutic avenues to mitigate cognitive decline and reduce risk of brain injury in patients with PAD. Various interventions, notably exercise, directly or indirectly improve systemic blood flow and oxygen supply and are effective strategies in patients with PAD or cognitive decline. Moreover, triggering protective cellular and systemic mechanisms by modulating inspired oxygen concentrations are emerging as potential novel treatment strategies. While several genetic and pharmacological approaches to modulate adaptations to hypoxia showed promising results in preclinical models of PAD, no clear benefits have yet been clinically demonstrated. We argue that genetic/pharmacological regulation of the involved adaptive systems remains challenging but that therapeutic variation of inspired oxygen levels (e.g., hypoxia conditioning) are promising future interventions to mitigate associated cognitive decline in patients with PAD.