Normobaric Hypoxia Research Articles

Effects of different exposures to normobaric hypoxia on cognitive performance in healthy young adults.: Normobaric hypoxia and cognitive performance.

Normobaric hypoxia has become an innovative non-pharmacological therapy to treat cognitive dysfunction. Nevertheless, the acute effects of exposure to hypoxia on cognitive performance remain unclear. We aimed to determine the effects of different normobaric hypoxic exposures on cognitive function in healthy young adults. Nineteen participants (13 men and 6 women; 23.7±3.9 years; 172.0±8.4 cm; 69.1±12.2 kg) completed a cross-over randomized control trial with the following doses of fraction of inspired oxygen (FiO2): a) 21%, b) 15%, c) 13% or d) 11%. During experimental trials, the physiological response (blood oxygen saturation and heart rate) and the following cognitive abilities were evaluated: memory, sustained attention, anticipation, and reaction time. Sustained attention improved under hypoxia at 15% FiO2 (mean difference (MD) 0.024, 95% confidence intervals (CI) 0.005 to 0.044 s; P=0.018) compared to 11% and 21% FiO2. During 11% and 15% FiO2, participants showed improved anticipation ability compared to normoxia (MD -0.023, 95% CI -0.042 to -0.003 s, P=0.020, and MD -0.009, 95% CI -0.016 to -0.001 s, P=0.022, respectively). However, reaction time was impaired under 11% compared to 21% FiO2 (MD 0.033, 95% CI 0.008 to 0.059 s, P=0.013). Finally, we did not find significant effects of hypoxia on memory (P>0.05). Severe normobaric hypoxic exposure (11% FiO2) produces detrimental effects on reaction time, although anticipation seems to be improved, compared to normoxia. In addition, cognitive processes of attention and anticipation appear to improve with moderate hypoxic exposure (15% FiO2).

Can hypoxic exercise retard cellular senescence? A narrative review.

Senescent cells are defined as normal cells that have undergone irreversible division arrest due to various factors. These cells have been found to play a pivotal role in aging and the development of chronic diseases. Numerous studies demonstrated that physical exercise is effective in anti-aging and anti-chronic diseases. Furthermore, the combination of exercise and hypoxia has been shown to optimize the stimulus of oxygen deprivation and extend cellular lifespan. This narrative review offers an exhaustive analysis of existing literature studying the effect of hypoxic exercise on cellular senescence under various conditions. Four electronic databases underwent title and abstract screening to summarize the effect of hypoxic exercise on cellular senescence under various conditions. Papers were deemed eligible if they examined the effect of hypoxic exercise on cellular senescence in full-text, peer-reviewed journals and published in English. The final search was carried out on May 4, 2024. Studied were excluded if they: (a) did not involve the utilization of hypoxic exercise as a sole intervention or a contributing factor; (b) did not investigate cellular senescence; (c) lacked sufficient information regarding the study design and findings. A total of 2033 articles were obtained from four databases. However, only 11 articles were deemed to meet eligibility criteria after thoroughly examining titles, abstracts, and full-text content. Authorship, publication year, details of the experimental subject, types of exercise, training protocols, organ, tissue or cell, markers of senescent cells examined, and their responses elicited by exercise were diligently recorded. This review identified 11 articles for data extraction. The sample sizes varied across a spectrum of complexity, ranging from 4 to 60 (Median=20). The studied population encompassed different healthy cohorts, which comprised sedentary males (n=6), trained males (n=2), mountain climbers (n=1), and older adults (n=2). Included studies preferred using bicycle ergometers (72.7%, n=8) as the exercise modality and 10 studies (90.9%) utilized hypoxia chambers to mimic a normobaric hypoxia environment. Four studies (36.4%) opted to utilize hypoxia chambers to mimic an altitude of 2733 and 4460 m. Additionally, 54.5% of studies (n=6) specifically investigated the effect of hypoxic exercise on lymphocytes, commonly utilizing CD28 (n=3) and CD57 (n=3) as markers of cellular senescence. Four studies (33.3%) examined the impact of hypoxic exercise on erythrocytes using CD47 as the marker for detecting senescent cells. These data support the notion that hypoxic exercise can retard cellular senescence of specific cells. In the future, standardization on the type of hypoxic exercise and markers of cellular senescence will be essential. Additionally, greater attention should be given to female populations and patients with different disease states. Lastly, further studies of the optimal form and dosage of exercise and the underlying cellular mechanisms are warranted. PROSPERO, identifier CRD42023431601.

Effects of a Combined Method of Normobaric Hypoxia on the Repeated Sprint Ability Performance of a Nine-Time World Champion Triathlete: A Case Report

Elite athletes are an under-represented population in scientific studies, and there are no works analysing the influence of hypoxia in elite triathletes. The aim of this study was to analyse the influence of different methods of normobaric hypoxia on repeated sprint ability (RSA) performance. This study was a case study with an elite triathlete who has won nine triathlon world championships. The study used a combination of different methods of normobaric hypoxia. The three methods combined were as follows: live high-train low interspersed; intermittent hypoxic training; and intermittent hypoxic exposure. This study analysed the influence of these methods on RSA performance in variables such as power output, saturation of muscular oxygen, heart rate and ventilatory variables (VO2 and VCO2). The triathlete was measured before the training protocol (PRE), just after (POST-D3) and 21 days after the end of the protocol (POST-D21). This type of protocol has shown that it can lead to an improvement in RSA performance in the number of sprints (PRE vs. POST-D3 vs. POST-D21: 19 vs. 24 vs. 28), power output (PRE 615 W vs. POST-D3 685 W vs. POST-D21 683W) and efficiency of the triathlete. This work may be useful in improving power output and repeated sprint ability for elite triathletes.

From oxygen shortage to neurocognitive challenges: behavioral patterns and imaging insights

Environmental hypoxia, resulting from reduced oxygen supply, poses a significant risk of dysfunctioning and damaging the neurocognitive system, particularly in relation to anxiety and stress. Inadequate oxygenation can lead to acute and chronic brain damage. Scholars used behavioral, hemodynamic, and electromagnetic neurofunctional techniques to investigate the effects of normobaric and hypobaric hypoxia on neurocognitive systems. They found a correlation between hypoxia, altered psychomotor responses, and changes in EEG alpha, theta, beta, and gamma rhythms, which affect spatial attention and memory. Hypoxia affects event related potential (ERP) components differently depending on latency. Perceptual responses N1 and P2 remain largely unaffected, while the amplitudes of preattentive MMN, vMMN, and P3a are significantly altered. Late latency components related to attention, particularly P3b, are also altered. These changes illustrate the spectrum from sensory detection to more complex cognitive processing, highlighting the brain's efficiency in managing information. Interestingly, the amplitudes of P3b, ADAN and CNV can increase with increased cognitive demands in hypoxia. This suggests a compensatory response. Prolonged exposure exacerbates these effects, resulting in compensatory delayed behavioral responses and alterations in behavioral monitoring and conflict inhibitory control, as reflected by reduced amplitudes in some attention related ERP components, including N2, N2pc, and ERN. Thus, neurocognitive function and integrity are under stress. ERP sources and hemodynamic images reveal that vulnerable brain regions include the frontal prefrontal cortices, hippocampus, basal ganglia, and parietal and visual cortices, which are essential for attention related processes like decision making and spatial memory. The auditory system appears less affected.

Respiratory Dysfunction and Abnormal Hypoxic Ventilatory Response in Mild to Moderate Parkinson's Disease.

Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases. We aimed to characterize respiratory dysfunction in mild to moderate PD. In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON-medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing FIO2 from 0.209 (room air) to 0.127, which was compared to eight age- and sex-matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45-min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF-medication to assess breathing responses. At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038-0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45-min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (-0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079). Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing.

Effects of two carbonic anhydrase inhibitors on exercise performance in acute hypoxia.

Acute mountain sickness occurs due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but inhibits exercise performance. Methazolamide (MZ), an analogous drug, has similar prophylactic benefits but does not impair isolated muscle mass exercise performance in normoxia. We sought to compare whole-body exercise performance in acute hypoxia (FIO2 = 0.15) between AZ, MZ and placebo (PLA). Fifteen healthy participants completed 5 testing visits: day 1 maximal exercise test, day 2 a familiarization, and days 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial performed after a 2-day dosing protocol of either AZ (250 mg t.i.d.), MZ (100 mg b.i.d.) or PLA (t.i.d.); the order was randomized and double-blinded. Prior to exercise, capillary blood samples were taken, and maximal voluntary contractions of quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest compared to PLA (capillary H+ 47±3, 43±2, 39±2 nmol for AZ, MZ and PLA respectively, p<0.01). Time to complete 5-km with PLA (562±32 seconds, p<0.01) was significantly faster than AZ and MZ (577±38 vs. 581±37s respectively), with no differences between AZ and MZ (p=0.96). There were no differences in average ventilation (124±27, 127±24, 127±19 l/min) and oxyhemoglobin saturation (87±2, 88±2, 88±3%) between AZ, MZ and PLA respectively (p>0.05). Overall, both AZ and MZ impair whole-body exercise performance in acute normobaric hypoxia.

Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction

The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS.

Normobaric hypoxia accelerates high-intensity intermittent training-induced mitochondrial biogenesis (PGC-1α)- and dynamics (OPA1)-related protein expressions in rat gastrocnemius muscle.

High-intensity intermittent training (HIIT) in a normobaric hypoxic environment enhances exercise capacity, possibly by increasing the mitochondrial content in skeletal muscle; however, the molecular mechanisms underlying these adaptations are not well understood. Therefore, we investigated whether HIIT under normobaric hypoxia can enhance the expression of proteins involved in mitochondrial biogenesis and dynamics in rat gastrocnemius muscle. Five-week-old male Wistar rats (n = 24) were randomly assigned to the following four groups: (1) sedentary under normoxia (20.9% O2) (NS), (2) training under normoxia (NT), (3) sedentary under normobaric hypoxia (14.5% O2) (HS), and (4) training under normobaric hypoxia (HT). The training groups in both conditions were engaged in HIIT on a treadmill five to six days per week for nine weeks. From the fourth week of the training period, the group assigned to hypoxic conditions was exposed to normobaric hypoxia. Forty-eight hours after completing the final training session, gastrocnemius muscles were surgically removed, and mitochondrial enzyme activity and mitochondrial biogenesis and dynamics regulatory protein levels were determined. Citrate synthase (CS) activity and mitochondrial oxygen phosphorylation (OXPHOS) subunits in the gastrocnemius muscle in the HT significantly exceeded those in the other three groups. Moreover, the levels of a master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and a mitochondrial fusion-related protein, optic atrophy 1 (OPA1), were significantly increased by HIIT under normobaric hypoxia. Our data indicates that HIIT and normobaric hypoxia increase the expression of mitochondrial biogenesis- and dynamics-related proteins in skeletal muscles.

β2-integrins control HIF1α activation in human neutrophils.

During inflammation, human neutrophils engage β2-integrins to migrate from the blood circulation to inflammatory sites with high cytokine but low oxygen concentrations. We tested the hypothesis that the inhibition of prolyl hydroxylase domain-containing enzymes (PHDs), cytokines, and β2-integrins cooperates in HIF pathway activation in neutrophils. Using either the PHD inhibitor roxadustat (ROX) (pseudohypoxia) or normobaric hypoxia to stabilize HIF, we observed HIF1α protein accumulation in adherent neutrophils. Several inflammatory mediators did not induce HIF1α protein but provided additive or even synergistic signals (e.g., GM-CSF) under pseudohypoxic and hypoxic conditions. Importantly, and in contrast to adherent neutrophils, HIF1α protein expression was not detected in strictly suspended neutrophils despite PHD enzyme inhibition and the presence of inflammatory mediators. Blocking β2-integrins in adherent and activating β2-integrins in suspension neutrophils established the indispensability of β2-integrins for increasing HIF1α protein. Using GM-CSF as an example, increased HIF1α mRNA transcription via JAK2-STAT3 was necessary but not sufficient for HIF1α protein upregulation. Importantly, we found that β2-integrins led to HIF1α mRNA translation through the phosphorylation of the essential translation initiation factors eIF4E and 4EBP1. Finally, pseudohypoxic and hypoxic conditions inducing HIF1α consistently delayed apoptosis in adherent neutrophils on fibronectin under low serum concentrations. Pharmacological HIF1α inhibition reversed delayed apoptosis, supporting the importance of this pathway for neutrophil survival under conditions mimicking extravascular sites. We describe a novel β2-integrin-controlled mechanism of HIF1α stabilization in human neutrophils. Conceivably, this mechanism restricts HIF1α activation in response to hypoxia and pharmacological PHD enzyme inhibitors to neutrophils migrating toward inflammatory sites.

Cardiorespiratory Responses to Exercise in Hypobaric versus Normobaric Hypoxia: A Randomized, Single-Blind, Crossover Study.

There is controversy whether there are meaningful physiological differences between hypobaric (HH) and normobaric hypoxia (NH). This study aimed to compare the cardiorespiratory responses to acute HH and NH under strictly controlled conditions. We hypothesized no differences at rest and during submaximal exercise, whereas during maximal exercise, a higher maximal ventilation (V̇Emax), peripheral oxygen saturation (SpO2) and maximal oxygen consumption (V̇O2max) in HH than in NH. In a randomized, single-blind, crossover design, eight young healthy subjects (three females) were studied in an environmental chamber in which either the barometric pressure (HH) or the inspired oxygen fraction (NH) was reduced to the equivalent of ~4000 m altitude. Measurements were taken at rest, during submaximal (moderate and high intensity) and maximal cycling exercise. All resting parameters were similar between HH and NH, except for a lower root mean square of the successive R-R interval differences in HH (p < 0.05). SpO2 was 2% higher in HH at all exercise intensities (p < 0.05). During submaximal exercise, minute ventilation was similar between HH and NH. However, HH yielded a 7% lower tidal volume during moderate-intensity exercise (p < 0.05) and a lower respiratory exchange ratio during high-intensity exercise (p < 0.01). V̇Emax and V̇O2max were 11% and 6% higher in HH, respectively (p < 0.01 for both). SpO2 at maximal exercise was positively correlated with V̇Emax, V̇Emax/V̇O2max and V̇O2max. The higher V̇O2max found in HH than in NH can be attributed to the higher V̇Emax counteracting desaturation at maximal exercise. Conversely, submaximal SpO2 improved in HH through mechanisms other than increased ventilation. These findings are likely due to respiratory muscle unloading in HH, which operated through different mechanisms depending on exercise intensity.

Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial

BackgroundCognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and the neurobiological underpinnings of such effects.MethodsIn sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimum n = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region.DiscussionThe results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies.Trial registrationClinicalTrials.gov, NCT06121206. Registered on 31 October 2023.

Normobaric Hypoxia Symptom Recognition in Three Training Sessions

INTRODUCTION: Hypoxia training is mandatory for military pilots, but variability in hypoxia symptoms challenges the training. In a previous study we showed that 64% of pilots recognized hypoxia faster in their second normobaric hypoxia session conducted 2.4 yr after the first. Our aim here was to evaluate whether a third session conducted 5.0 yr after the first would provide further benefit. METHODS: This study was conducted under normobaric conditions in a tactical F/A-18C Hornet simulator in three sessions in which the pilots performed visual identification missions and breathed 21% oxygen in nitrogen. The breathing gas was changed to a hypoxic mixture containing either 8%, 7%, or 6% oxygen in nitrogen without the pilot’s knowledge. Data were collected from 102 military pilots. The primary outcome was the time taken for initial identification of hypoxia symptoms. RESULTS: Hypoxia symptoms were recognized on average in the first session in 8% oxygen in 100 s, 7% oxygen in 90 s, and 6% oxygen in 78 s; in the second in 87 s, 80 s, and 71 s, respectively; and in the third in 79 s, 67 s, and 64 s, respectively. In 2 sessions 20 pilots and in each 3 training sessions 3 pilots had slow recognition times. DISCUSSION: Hypoxia symptom recognition improved the further the repeated normobaric hypoxia training went. More emphasis should be put on the 23% group of slow hypoxia symptom recognizers and more customized hypoxia training for them should be offered. Leinonen AM, Varis NO, Kokki HJ, Leino TK. Normobaric hypoxia symptom recognition in three training sessions. Aerosp Med Hum Perform. 2024; 95(10):758–764.

Repeated Short Cold-water Immersions Are Sufficient To Habituate To The Cold, But Do Not Lead To Adaptations During Exercise In Normobaric Hypoxia

Repeated Short Cold-water Immersions Are Sufficient To Habituate To The Cold, But Do Not Lead To Adaptations During Exercise In Normobaric Hypoxia

Reaction of young physically active men with early repolarization phenomena on a cycle of inhalations of a hypoxic gas mixture

Aim: To examine a reaction of young physically active men with early repolarization phenomena (ERP) on an inhalation of a hypoxic gas mixture (IHGM).Material and Methods.17 men (6 with ERP &amp; 11 without it) participated in our study. ECG, echocardiography, clinical blood test and erythropoietin blood test were carried out to every of them initially and on the 1-st and 10-th days after the IHGM.Results. It was found that end systolic volume was 13,8% more (р = 0,01) and ejection fraction was 8% less (р = 0,01) in ERP group than in non ERP group. These indicators were not change after IHGM. In ERP group on 1-st day after IHGM erythropoietin concentration was 79% more (р = 0,027) and on a 10-th day was 64% more (р = 0,003) than in non-ERP group. In ERP group high fluorescent reticulocyte count on a 1-st day after IHGM was 69% more (р = 0,03) and middle fluorescent reticulocyte count on a 10-th day after IHGM was 13% more (р = 0,04) than in non-ERP group. On a 10-th day after IHGM hematocrit and hemoglobin concentration were 5% (р = 0,01) and 12% (р = 0,01) less than in non ERP group.Conclusion. Thus, men with ERP have a pronounced reaction of the erythropoiesis system on normobaric hypoxia.

Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.

Background: The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Objectives: Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. Methods: MSCs were exposed four days per week, two hours/day, to hypoxia (3% O2) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. Results: early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Conclusions: Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

Impact of the Menstrual Cycle on the Cardiovascular and Ventilatory Responses During Exercise in Normoxia and Hypoxia.

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 (FiO2 = 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.

Effects of 4 weeks of device-induced normobaric intermittent hypoxia/hyperoxia training on the performance of elite cyclists: A pilot study

Introduction &amp; Purpose Classic altitude training and other forms of hypoxia are regularly used in endurance training (Mujika et al., 2019). Due to corona exit restrictions in 2019-2020, device-induced normobaric hypoxia/hyperoxia was suggested as an alternative to classic altitude training. Intermittent hypoxia/hyperoxia training (IHHT) has been studied and used in various forms since the 1940s (Serebrovskaya, 2002) with the advantage to be used at the athlete’s training site (Burtscher, 2005). The aim of this pilot study was to test the effects of a IHHT intervention on aerobic performance, hematological parameters and hypoxia-induced factor-1α (HIF-1α). Method A total of 11 athletes (2 women) from the U23 and elite national squads of the Austrian Cycling Federation completed 16 IHHT units in addition to their normal training program over a period of 4 weeks as part of a randomized cross over intervention study (control – IHHT, IHHT – control). The IHHT units were carried out on a Cellgym CellAir® Gecko Plus device at rest without exercise following a predetermined protocol (Sessions 1-8: 5 min of hypoxia (12.0% oxygen) followed by 3 min of hyperoxia (34.0% oxygen) repeated five times. Sessions 9-16): 6 min of hypoxia (11.0% oxygen) followed by 3 min of hyperoxia (34.0% oxygen). During the 4 weeks of control period, participants should maintain their training schedule. Aerobic performance was determined before and after the intervention by spiroergometry. As secondary outcomes, changes in hematological parameters and protein levels of HIF-1α were determined from venous blood which was processed immediately after collection. Serum was stored at -80 °C until HIF-1 α determination by ELISA technique. Results Eleven out of 13 athletes took part in the pre – post IHHT measurements, but only three of them managed to participate in the measurements planned for the control period, making it impossible to compare the two conditions. Replacement was not possible due to the availability of candidates and the ongoing preparation for the season. After 4 weeks of intervention with 16 IHHT training sessions, no significant changes were observed in performance parameters such as VO2peak, relative VO2max, maximum power (watts) or threshold values (p &gt; 0.05). There were also no significant changes in blood enzymes, lipid and iron metabolism (p &gt; 0.05). However, a tendency towards increased values of haemoglobin (z = 1.738; p = 0.082) and a significant increase of erythrocyte counts (z = 2.193; p = 0.028) were detected. Other haematological parameters and HIF-1α did not change significantly (p &gt; 0.05). Discussion &amp; Conclusion In summary, four weeks of device-induced normobaric IHHT had a modest effect on haematological parameters, but with no detectable transfer to maximal or submaximal endurance performance in highly trained athletes. Although various studies have shown that the difference between normobaric and hypobaric hypoxia exposure is not limited to the partial pressure of oxygen, but Mounier and Brugniaux state that the physiological responses are in fact equivalent (Mounier &amp; Brugniaux, 2012). However, due to the limitations of the competitive setting and the low sample size, the final interpretation of the study remains difficult. References Burtscher, M. (2005). Intermittierende Hypoxie: Höhenvorbereitung, Training, Therapie [Intermittent hypoxia: altitude preparation, training, therapy]. Schweizerische Zeitschrift für Sportmedizin und Sporttraumatologie, 53(2), 61-67. Serebrovskaya, T. V. (2002). Intermittent hypoxia research in the former Soviet Union and the commonwealth of independent states: History and review of the concept and selected applications. High Altitude Medicine &amp; Biology, 3(2), 205-221. https://doi.org/10.1089/15270290260131939 Mounier, R., &amp; Brugniaux, J. V. (2012). Counterpoint: Hypobaric hypoxia does not induce different responses from normobaric hypoxia. Journal of Applied Physiology, 112(10), 1784-1786. https://doi.org/10.1152/japplphysiol.00067.2012a Mujika, I., Sharma, A. P., &amp; Stellingwerff, T. (2019). Contemporary periodization of altitude training for elite endurance athletes: A narrative review. Sports Medicine, 49, 1651-1669. https://doi.org/10.1007/s40279-019-01165-y

Effects of 12 Weeks of Combined Exercise Training in Normobaric Hypoxia on Arterial Stiffness, Inflammatory Biomarkers, and Red Blood Cell Hemorheological Function in Obese Older Women.

The present study examined the effect of 12-week combined exercise training in normobaric hypoxia on arterial stiffness, inflammatory biomarkers, and red blood cell (RBC) hemorheological function in 24 obese older women (mean age: 67.96 ± 0.96 years). Subjects were randomly divided into two groups (normoxia (NMX; n = 12) and hypoxia (HPX; n = 12)). Both groups performed aerobic and resistance exercise training programs three times per week for 12 weeks, and the HPX group performed exercise programs in hypoxic environment chambers during the intervention period. Body composition was estimated using bioelectrical impedance analysis equipment. Arterial stiffness was measured using an automatic waveform analyzer. Biomarkers of inflammation and oxygen transport (tumor necrosis factor alpha, interleukin 6 (IL-6), erythropoietin (EPO), and vascular endothelial growth factor (VEGF)), and RBC hemorheological parameters (RBC deformability and aggregation) were analyzed. All variables showed significantly more beneficial changes in the HPX group than in the NMX group during the intervention. The combined exercise training in normobaric hypoxia significantly reduced blood pressure (systolic blood pressure: p < 0.001, diastolic blood pressure: p < 0.001, mean arterial pressure: p < 0.001, pulse pressure: p < 0.05) and brachial-ankle pulse wave velocity (p < 0.001). IL-6 was significantly lower in the HPX group than in the NMX group post-test (p < 0.001). Also, EPO (p < 0.01) and VEGF (p < 0.01) were significantly higher in the HPX group than in the NMX group post-test. Both groups showed significantly improved RBC deformability (RBC EI_3Pa) (p < 0.001) and aggregation (RBC AI_3Pa) (p < 0.001). The present study suggests that combined exercise training in normobaric hypoxia can improve inflammatory biomarkers and RBC hemorheological parameters in obese older women and may help prevent cardiovascular diseases.

Acute normobaric hypoxia causes a rightward shift in the torque-frequency relationship but has no effect on postactivation potentiation.

Low fractions of inspired oxygen ([Formula: see text]; i.e., hypoxia) affect aspects of skeletal muscle contractility in humans, but it remains unclear if postactivation potentiation (PAP) and the torque-frequency (T-F) relationship are altered. We investigated the effects of 2 (H2) and 4 (H4) h of normobaric hypoxia ([Formula: see text] = 0.11 ± 0.47) on the magnitude of PAP of the knee extensors and the T-F relationship of the dorsiflexors in 13 and 12 healthy participants, respectively. To assess PAP, a resting twitch was evoked via femoral nerve stimulation before and 2-300 s after a 10-s maximal voluntary contraction (MVC). A T-F relationship was obtained by stimulating the common fibular nerve with a single pulse and 1-s trains between 5 and 100 Hz. During hypoxia, peripheral oxygen saturation decreased by ∼18% from 98.0 ± 0.8% at baseline (P < 0.001). MVC force and voluntary activation (VA) of the knee extensors were lower than baseline throughout hypoxia (e.g., ∼8% and ∼5%, respectively, at H2; P ≤ 0.027); however, the magnitude of PAP was not altered by hypoxia (P ≥ 0.711). Surprisingly, PAP did increase with time across the control day (P ≤ 0.012). MVC torque and VA of the dorsiflexors were unaffected by hypoxia (P ≥ 0.127), but the estimated frequency required to evoke 50% of 100 Hz torque increased by ∼1.2 Hz at H2 (P ≤ 0.021). These results imply that 2 h of normobaric hypoxia were sufficient to 1) impair neural drive to the knee extensors but not the mechanism(s) responsible for PAP and 2) lead to a rightward shift of the T-F relationship for the dorsiflexors.NEW & NOTEWORTHY Postactivation potentiation of the knee extensors was unaffected by 4 h of normobaric hypoxia exposure but may be confounded by hypoxia-related impairments to the conditioning contraction. In the dorsiflexors, contractile rates increased in hypoxia, which led to a rightward shift of the torque-frequency relationship, such that a higher frequency was required to obtain 50% of maximal torque. These results expand our understanding of the acute effects of hypoxia on skeletal muscle function.

Metabolic and hormonal responses to acute high-load resistance exercise in normobaric hypoxia using a saturation clamp.

We assessed metabolic and hormonal responses to high-load resistance exercise under varying normobaric hypoxia conditions with a saturation clamp. Employing a counterbalanced, crossover test design, ten well-trained men participated in three exercise trials with normoxic or hypoxic gas mixtures to maintain arterial oxygen saturation at -90% and 80% [moderate (MH) and severe (SH) hypoxia, respectively]. The resistance exercise regimen comprised five sets of 10 repetitions of barbell back squats at 70% of one repetition maximum, with 1-min rest between sets. Metabolic and hormonal responses were measured before normoxia or hypoxia exposures (Pre 1), 15min after the exposures (Pre 2), and at 0-, 15-, and 30-min post-exercises (T0, T15, and T30, respectively). Compared to Pre 2, blood lactate concentrations and growth hormone values were elevated at T0, T15, and T30 (p ≤ 0.001), while testosterone values increased at T0 in all conditions (p ≤ 0.009). Epinephrine values increased significantly from Pre 2 to T0 in SH only (p < 0.001). SH had significantly higher blood lactate concentrations (p = 0.023), growth hormone (p = 0.050), and epinephrine (p = 0.020) values at T30 compared to NM. Cortisol values were elevated above Pre 2at T15 in MH and SH, while lower testosterone values were noted at T0 and T15 for SH compared to NM and MH (all p ≤ 0.05). Severe simulated hypoxia, achieved through a saturation clamp during barbell back squats, may enhance metabolic and hormonal responses, particularly 30min post-session. Nevertheless, the acute effects of hypoxia exposure seem to be overridden by the impact of high-load resistance exercise.