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PURPOSE: We investigated the effects of manipulating running velocity and hypoxic exposure on vastus lateralis muscle oxygenation levels during treadmill running. METHODS: Eleven trained male distance runners performed 7 randomized runs at different velocities (8, 10, 12, 14, 16, 18, and 20 km·h-1), each lasting 45 seconds on an instrumented treadmill in normoxia (fraction of inspired oxygen [FiO2] = 20.9%), moderate hypoxia (FiO2 = 16.1%), high hypoxia (FiO2 = 14.1%), and severe hypoxia (FiO2 = 13.0%). Continuous assessment of Tissue Saturation Index (TSI) in the vastus lateralis muscle was conducted using near-infrared spectroscopy. Subsequently, changes in TSI (ΔTSI) data over the final 20 seconds of each run were compared between velocities and conditions. RESULTS: There was a significant velocity × condition interaction for ΔTSI% (P < .001, ηp2=.19), with a smaller ΔTSI% decline in normoxia compared with high hypoxia and severe hypoxia at 8 km·h-1 (g = 1.30 and 1.91, respectively), 10 km·h-1 (g = 0.75 and 1.43, respectively), and 12 km·h-1 (g = 1.47 and 1.95, respectively) (pooled values for all conditions: P < .037). The ΔTSI% decline increased with each subsequent velocity increment from 8 km·h-1 (-9.2% [3.7%]) to 20 km·h-1 (-22.5% [4.1%]) irrespective of hypoxia severity (pooled values for all conditions: P < .048). CONCLUSIONS: Running at slower velocities in conjunction with high and severe hypoxia reduces vastus lateralis muscle oxygenation levels. Muscle ΔTSI% proves to be a sensitive indicator, underscoring the potential use of near-infrared spectroscopy as a reference index of internal load during treadmill runs.

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Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. To study the role of hypoxic sympathetic activation, we investigated the effects of hypoxia with and without adrenergic blockade (AB) on cardiovascular dysfunction and lung injury, i.e., pulmonary edema, congestion, inflammation, and nitrosative stress. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol, or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function in both normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor α (TNFα) and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB markedly reduced both TNFα and nitrotyrosine. However, AB did not attenuate PE. The results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into the pulmonary circulation, thus promoting PE.

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In an increasingly aging and overweight population, osteoporosis and type 2 diabetes (T2DM) are major public health concerns. T2DM patients experience prejudicial effects on their bone health, affecting their physical capacity. Exercise in hypoxia (EH) and a low-carbohydrate diet (LCD) have been suggested for therapeutic benefits in T2DM, improving bone mineral content (BMC) and glycemic control. This study investigated the effects of EH combined with an LCD on body composition and functional and physiologic capacity in T2DM patients. Older T2DM patients (n = 42) were randomly assigned to the following groups: (1) control group: control diet + exercise in normoxia; (2) EH group: control diet + EH; (3) intervention group: LCD + EH. Cardiopulmonary tests (BRUCE protocol), body composition (DEXA), and functional capacity (6MWT, handgrip strength) were evaluated. Body mass index (kg/m2) and body fat (%) decreased in all groups (p < 0.001). BMC (kg) increased in all groups (p < 0.001) and was significantly higher in the EH and EH + LCD groups (p < 0.001). VO2peak improved in all groups (p < 0.001), but more so in the hypoxia groups (p = 0.019). Functional capacity was increased in all groups (p < 0.001), but more so in the EH group in 6MWT (p = 0.030). EH with and without an LCD is a therapeutic strategy for improving bone mass in T2DM, which is associated with cardiorespiratory and functional improvements.

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The aim of this work was to analyze the influence of acute normobaric hypoxia on quadricep oxygenation. Muscle oxygen saturation (SmO2) was measured using near-infrared spectrometry (NIRS) technology during a normobaric hypoxia tolerance test (NHTT). SmO2 was measured with a Humon Hex® device. In total, 54 healthy subjects participated, 68.5 of which were males and 31.5% of which were females. They performed an NHTT with the IAltitude® simulator, breathing air with an FiO2 level of 11% (equivalent to 5050 m). The maximum duration of the NHTT was set at 10 min, stopping if it reached 83% SpO2. The initial values (PRE) were compared with those obtained at the end of the test (POST) and after 10 min of recovery. The participants were divided into two groups based on whether (G1) they completed the ten minutes or not (G2). In total, 35.1% of men and 41.2% of women completed the 10 min. In both groups, significant differences were observed in the decrease in SmO2 values (p < 0.0001) (G1: PRE = 59.5 ± 12.48%; POST = 55.95 ± 14.30%; G2: PRE = 60.06 ± 13.46%; POST = 57.2 ± 12.3%). There were no differences between groups in any of the three periods. Exposure to normobaric hypoxia produces a decrease in quadricep levels of SmO2 in both sexes, regardless of whether the test is completed. Two patterns appeared: A.-less time and more hypoxia; B. a longer duration and less hypoxia.

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PURPOSE: To investigate the influence of acute normobaric hypoxia on standing balance under single and dual-task conditions, both with and without visual input. METHODS: 20 participants (7 female, 20-31 years old) stood on a force plate for 16, 90-s trials across four balance conditions: single-task (quiet stance) or dual-task (auditory Stroop test), with eyes open or closed. Trials were divided into four oxygen conditions where the fraction of inspired oxygen (FIO2) was manipulated (normoxia: 0.21 and normobaric hypoxia: 0.16, 0.145 and 0.13 FIO2) to simulate altitudes of 1100, 3,400, 4300, and 5200 m. Participants breathed each FIO2 for ~ 3 min before testing, which lasted an additional 7-8 min per oxygen condition. Cardiorespiratory measures included heart rate, peripheral blood oxygen saturation, and pressure of end tidal (PET) CO2 and O2. Center of pressure measures included total path length, 95% ellipse area, and anteroposterior and mediolateral velocity. Auditory Stroop test performance was measured as response accuracy and latency. RESULTS: Significant decreases in oxygen saturation and PETO2, and increased heart rate were observed between normoxia and normobaric hypoxia (P < 0.0001). Total path length was higher at 0.13 compared to 0.21 FIO2 for the eyes closed no Stoop test condition (P = 0.0197). No other significant differences were observed. CONCLUSION: These findings suggest that acute normobaric hypoxia has a minimal impact on standing balance and does not influence auditory Stroop test or dual-task performance. Further investigation with longer exposure is required to understand the impact and time course of normobaric hypoxia on standing balance.

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The present study aimed to investigate the effects of a short period of normobaric hypoxic exposure on spatial learning and memory, and brain-derived neurotrophic factor (BDNF) levels in the rat hippocampus. Hypoxic conditions were set at 12.5% O2. We compared all variables between normoxic trials (Norm), after 24 h (Hypo-24 h), and after 72 h of hypoxic exposure (Hypo-72 h). Spatial learning and memory were evaluated by using a water-finding task in an open field. Time to find water drinking fountains was significantly extended in Hypo 24 h (36.2 ± 21.9 s) compared to those in Norm (17.9 ± 12.8 s; P < 0.05), whereas no statistical differences between Norm and Hypo-72 h (22.7 ± 12.3 s). Moreover, hippocampal BDNF level in Hypo-24 h was significantly lower compared to Norm (189.4 ± 28.4 vs. 224.9 ± 47.7 ng/g wet tissue, P < 0.05), whereas no statistically differences in those between Norm and Hypo-72 h (228.1 ± 39.8 ng/g wet tissue). No significant differences in the changes in corticosterone and adrenocorticotropic hormone levels were observed across the three conditions. When data from Hypo-24 h and Hypo-72 h of hypoxia were pooled, there was a marginal negative relationship between the time to find drinking fountains and BDNF (P < 0.1), and was a significant negative relationship between the locomotor activities and BDNF (P < 0.05). These results suggest that acute hypoxic exposure (24 h) may impair spatial learning and memory; however, it recovered after 72 h of hypoxic exposure. These changes in spatial learning and memory may be associated with changes in the hippocampal BDNF levels in rats.

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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.

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This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80-200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day-1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition.

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BACKGROUND: Obesity, a common lifestyle-related condition, is correlated with factors like inadequate physical activity. Its connection to diverse health issues presents a significant challenge to healthcare. This pilot study investigated the effects of hypoxic training on aerobic capacity and biometric-structural indicators in obese women. The secondary objective was to determine the feasibility, effectiveness, and safety of the planned research procedures and their potential for larger-scale implementation. MATERIAL AND METHODS: Forty-one non-trained women with first-degree obesity were randomly assigned to even normobaric hypoxic training (H + E), normoxic training (E), passive exposure to hypoxia (H), and a control group (C). Training sessions were conducted three times a week for four weeks (12 training sessions). Body composition parameters were assessed, metabolic thresholds were determined, and maximal oxygen consumption (VO2max) was measured before and after interventions. RESULTS: The results demonstrated that training in hypoxic conditions significantly affected somatic parameters, with the H + E group achieving the best outcomes in terms of weight reduction and improvements in body composition indicators (p < 0.001). Normoxic training also induced a positive impact on body weight and body composition, although the results were less significant compared to the H + E group (p < 0.001). Additionally, training in hypoxic conditions significantly improved the aerobic capacity among the participants (p < 0.001). The H + E group achieved the best results in enhancing respiratory endurance and oxygen consumption (p < 0.001). CONCLUSIONS: The results of this pilot study suggest, that hypoxic training can be effective for weight reduction and improving the aerobic capacity in obese women. Despite study limitations, these findings indicate that hypoxic training could be an innovative approach to address obesity and related conditions. Caution is advised in interpreting the results, considering both the strengths and limitations of the pilot study. Before proceeding to a larger-scale study, the main study should be expanded, including aspects such as dietary control, monitoring physical activity, and biochemical blood analysis.

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Acute exposure to hypoxia can lead to cognitive impairment. Therefore, hypoxia may become a safety concern for occupational or recreational settings at altitude. Cognitive tests are used as a tool to assess the degree to which hypoxia affects cognitive performance. However, so many different cognitive tests are used that comparing studies is challenging. This structured literature evaluation provides an overview of the different cognitive tests used to assess the effects of acute hypoxia on cognitive performance in healthy volunteers. Less frequently used similar cognitive tests were clustered and classified into domains. Subsequently, the different cognitive test clusters were compared for sensitivity to different levels of oxygen saturation. A total of 38 articles complied with the selection criteria, covering 86 different cognitive tests. The tests and clusters showed that the most consistent effects of acute hypoxia were found with the Stroop test (where 42% of studies demonstrated significant abnormalities). The most sensitive clusters were auditory/verbal memory: delayed recognition (83%); evoked potentials (60%); visual/spatial delayed recognition (50%); and sustained attention (47%). Attention tasks were not particularly sensitive to acute hypoxia (impairments in 0%-47% of studies). A significant hypoxia level-response relationship was found for the Stroop test (p = 0.001), as well as three clusters in the executive domain: inhibition (p = 0.034), reasoning/association (p = 0.019), and working memory (p = 0.024). This relationship shows a higher test sensitivity at more severe levels of hypoxia, predominantly below 80% saturation. No significant influence of barometric pressure could be identified in the limited number of studies where this was varied. This review suggests that complex and executive functions are particularly sensitive to hypoxia. Moreover, this literature evaluation provides the first step towards standardization of cognitive testing, which is crucial for a better understanding of the effects of acute hypoxia on cognition.

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The muscle molecular adaptations to different exercise intensities in combination with hypoxia are not well understood. This study investigated the effect of low- and supramaximal-intensity hypoxic training on muscle metabolic gene expression in mice. C57BL/6 mice were divided into two groups: sedentary and training. Training consisted of 4 weeks at low or supramaximal intensity, either in normoxia or hypoxia (FiO2 = 0.13). The expression levels of genes involved in the hypoxia signaling pathway (Hif1a and Vegfa), the metabolism of glucose (Gys1, Glut4, Hk2, Pfk, and Pkm1), lactate (Ldha, Mct1, Mct4, Pdh, and Pdk4) and lipid (Cd36, Fabp3, Ucp2, Hsl, and Mcad), and mitochondrial energy metabolism and biogenesis (mtNd1, mtNd6, CytC, CytB, Pgc1a, Pgc1ß, Nrf1, Tfam, and Cs) were determined in the gastrocnemius muscle. No physical performance improvement was observed between groups. In normoxia, supramaximal intensity training caused upregulation of major genes involved in the transport of glucose and lactate, fatty acid oxidation, and mitochondrial biogenesis, while low intensity training had a minor effect. The exposure to hypoxia changed the expression of some genes in the sedentary mice but had a moderate effect in trained mice compared to respective normoxic mice. In hypoxic groups, low-intensity training increased the mRNA levels of Mcad and Cs, while supramaximal intensity training decreased the mRNA levels of Mct1 and Mct4. The results indicate that hypoxic training, regardless of exercise intensity, has a moderate effect on muscle metabolic gene expression in healthy mice.

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BACKGROUND: The effects of hypoxia conditioning, which involves recurrent exposure to hypoxia combined with exercise training, on improving body composition in the ageing population have not been extensively investigated. OBJECTIVE: This meta-analysis aimed to determine if hypoxia conditioning, compared to similar training near sea level, maximizes body composition benefits in middle-aged and older adults. METHODS: A literature search of PubMed, EMBASE, Web of Science, Scopus and CNKI (China National Knowledge Infrastructure) databases (up to 27th November 2022) was performed, including the reference lists of relevant papers. Three independent reviewers extracted study characteristics and health outcome measures. Search results were limited to original studies of the effects of hypoxia conditioning on body composition in middle-aged and older adults. RESULTS: Twelve studies with a total of 335 participants were included. Hypoxia conditioning induced greater reductions in body mass index (MD = -0.92, 95%CI: -1.28 to -0.55, I2 = 0%, p < 0.00001) and body fat (SMD = -0.38, 95%CI: -0.68 to -0.07, I2 = 49%, p = 0.01) in middle-aged and older adults compared with normoxic conditioning. Hypoxia conditioning improved lean mass with this effect not being larger than equivalent normoxic interventions in either middle-aged or older adults (SMD = 0.07, 95%CI -0.12 to 0.25, I2 = 0%, p = 0.48). Subgroup analysis showed that exercise in moderate hypoxia (FiO2 > 15%) had larger effects than more severe hypoxia (FiO2 ≤ 15%) for improving body mass index in middle-aged and older adults. Hypoxia exposure of at least 60 min per session resulted in larger benefits for both body mass index and body fat. CONCLUSION: Hypoxia conditioning, compared to equivalent training in normoxia, induced greater body fat and body mass index improvements in middle-aged and older adults. Adding hypoxia exposure to exercise interventions is a viable therapeutic solution to effectively manage body composition in ageing population.

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Introduction: The ability to metabolize fructose to bypass the glucose pathway in near-anaerobic conditions appears to contribute to the extreme hypoxia tolerance of the naked-mole rats. Therefore, we hypothesized that exogenous fructose could improve endurance capacity and cognitive performance in humans exposed to hypoxia. Methods: In a randomized, double-blind, crossover study, 26 healthy adults (9 women, 17 men; 28.8 ± 8.1 (SD) years) ingested 75 g fructose, 82.5 g glucose, or placebo during acute hypoxia exposure (13% oxygen in a normobaric hypoxia chamber, corresponding to oxygen partial pressure at altitude of ~3,800 m) on separate days. We measured exercise duration, heart rate, SpO2, blood gasses, and perceived exertion during a 30-min incremental load test followed by Farnsworth-Munsell 100 Hue (FM-100) color vision testing and the unstable tracking task (UTT) to probe eye-hand coordination performance. Results: Exercise duration in hypoxia was 21.13 ± 0.29 (SEM) min on fructose, 21.35 ± 0.29 min on glucose, and 21.35 ± 0.29 min on placebo (p = 0.86). Heart rate responses and perceived exertion did not differ between treatments. Total error score (TES) during the FM-100 was 47.1 ± 8.0 on fructose, 45.6 ± 7.6 on glucose and 53.3 ± 9.6 on placebo (p = 0.35) and root mean square error (RMSE) during the UTT was 15.1 ± 1.0, 15.1 ± 1.0 and 15.3 ± 0.9 (p = 0.87). Discussion: We conclude that oral fructose intake in non-acclimatized healthy humans does not acutely improve exercise performance and cognitive performance during moderate hypoxia. Thus, hypoxia tolerance in naked mole-rats resulting from oxygen-conserving fructose utilization, cannot be easily reproduced in humans.

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Introduction: At cruising altitude, the cabin pressure of passenger aircraft needs to be adjusted and, therefore, the oxygen content is equivalent to ambient air at 2,500 masl, causing mild desaturation and a rising pulmonary vascular resistance (PVR) in healthy subjects. For Fontan patients with passive pulmonary perfusion, a rising PVR can cause serious medical problems. The purpose of this fitness to fly investigation (FTF) is to assess the risk of air travel for children and adolescents after Fontan palliation. Methods: We investigated 21 Fontan patients [3-14y] in a normobaric hypoxic chamber at a simulated altitude of 2,500 m for 3 h. Oxygen saturation, heart rate, and regional tissue saturation in the forehead (NIRS) were measured continuously. Before entering the chamber, after 90 and 180 min in the hypoxic environment, blood gas analysis and echocardiography were performed. Results: Heart rate and blood pressure did not show significant intraindividual changes. Capillary oxygen saturation (SaO2) decreased significantly after 90 min by a mean of 5.6 ± 2.87% without further decline. Lactate, pH, base excess, and tissue saturation in the frontal brain did not reach any critical values. In the case of open fenestration between the tunnel and the atrium delta, P did not increase, indicating stable pulmonary artery pressure. Conclusion: All 21 children finished the investigation successfully without any adverse events, so flying short distance seems to be safe for most Fontan patients with good current health status. As the baseline oxygen saturation does not allow prediction of the maximum extent of desaturation and adaption to a hypoxic environment takes up to 180 min, the so-called hypoxic challenge test is not sufficient for these patients. Performing an FTF examination over a period of 180 min allows for risk assessment and provides safety to the patients and their families, as well as the airline companies.

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In rats, acute normobaric hypoxia depressed left ventricular (LV) inotropic function. After 24 h of hypoxic exposure, a slight recovery of LV function occurred. We speculated that prolonged hypoxia (72 h) would induce acclimatization and, hence, recovery of LV function. Moreover, we investigated biomarkers of nitrosative stress and apoptosis as possible causes of hypoxic LV depression. To elucidate the role of hypoxic sympathetic activation, we studied whether adrenergic blockade would further deteriorate the general state of the animals and their cardiac function. Ninety-four rats were exposed over 72 h either to normal room air (N) or to normobaric hypoxia (H). The rodents received infusion (0.1 mL/h) with 0.9% NaCl or with different adrenergic blockers. Despite clear signs of acclimatization to hypoxia, the LV depression continued persistently after 72 h of hypoxia. Immunohistochemical analyses revealed significant increases in markers of nitrosative stress, adenosine triphosphate deficiency and apoptosis in the myocardium, which could provide a possible explanation for the absence of LV function recovery. Adrenergic blockade had a slightly deteriorative effect on the hypoxic LV function compared to the hypoxic group with maintained sympathetic efficacy. These findings show that hypoxic sympathetic activation compensates, at least partially, for the compromised function in hypoxic conditions, therefore emphasizing its importance for hypoxia adaptation.

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PURPOSE: We aimed to investigate respiratory rate variability (RRV) and tidal volume (Vt) variability during exposure to normobaric hypoxia (i.e., reduction in the fraction of inspired oxygen - FiO2), and the association of the changes in RRV and Vt variability with the changes in pulse oxygen saturation (SpO2). METHODS: Thirty healthy human participants (15 females) were exposed to: (1) 15-min normoxia, (2) 10-min hypoxia simulating 2200 m, (3) 10-min hypoxia simulating 4000 m, (4) 10-min hypoxia simulating 5000 m, (5) 15-min recovery in normoxia. Linear regression modelling was applied with SpO2 (dependent variable) and the changes in RRV and Vt variability (independent variables), controlling for FiO2, age, sex, changes in heart rate (HR), changes in HR variability (HRV), and changes in minute ventilation (VE). RESULTS: When modelling breathing parameter variability as root-mean-square standard deviation (RMSSD), a significant independent association of the changes in RRV with the changes in SpO2 was found (B = -4.3e-04, 95% CI = -8.3e-04/-2.1e-05, p = 0.04). The changes in Vt variability showed no significant association with the changes in SpO2 (B = -1.6, 95% CI = -5.5/2.4, p = 0.42). When modelling parameters variability as SD, a significant independent association of the changes in RRV with the changes in SpO2 was found (B = -8.2e-04, 95% CI = -1.5e-03/-9.4e-05, p = 0.03). The changes in Vt variability showed no significant association with the changes in SpO2 (B=1.4, 95% CI = -5.8/8.6, p = 0.69). CONCLUSION: Higher RRV is independently associated with lower SpO2 during acute hypoxic exposure, while Vt variability parameters are not. Therefore, RRV may be a potentially interesting parameter to characterize individual responses to acute hypoxia.

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PURPOSE: To investigate whether 4 weeks of normobaric "live high-train low and high" (LHTLH) causes different hematological, cardiorespiratory, and sea-level performance changes compared to living and training in normoxia during a preparation season. METHODS: Nineteen (13 women, 6 men) cross-country skiers competing at the national or international level completed a 28-day period (∼18 h day-1 ) of LHTLH in normobaric hypoxia of ∼2400 m (LHTLH group) including two 1 h low-intensity training sessions per week in normobaric hypoxia of 2500 m while continuing their normal training program in normoxia. Hemoglobin mass (Hbmass ) was assessed using a carbon monoxide rebreathing method. Time to exhaustion (TTE) and maximal oxygen uptake (VO2max ) were measured using an incremental treadmill test. Measurements were completed at baseline and within 3 days after LHTLH. The control group skiers (CON) (seven women, eight men) performed the same tests while living and training in normoxia with ∼4 weeks between the tests. RESULTS: Hbmass in LHTLH increased 4.2 ± 1.7% from 772 ± 213 g (11.7 ± 1.4 g kg-1 ) to 805 ± 226 g (12.5 ± 1.6 g kg-1 ) (p < 0.001) while it was unchanged in CON (p = 0.21). TTE improved during the study regardless of the group (3.3 ± 3.4% in LHTLH; 4.3 ± 4.8% in CON, p < 0.001). VO2max did not increase in LHTLH (61.2 ± 8.7 mL kg-1 min-1 vs. 62.1 ± 7.6 mL kg-1 min-1 , p = 0.36) while a significant increase was detected in CON (61.3 ± 8.0-64.0 ± 8.1 mL kg-1 min-1 , p < 0.001). CONCLUSIONS: Four-week normobaric LHTLH was beneficial for increasing Hbmass but did not support the short-term development of maximal endurance performance and VO2max when compared to the athletes who lived and trained in normoxia.

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BACKGROUND: Aging is a degenerative process that is associated with an increased risk of diseases. Intermittent hypoxia has been investigated in reference to performance and health-related functions enhancement. This systematic review aimed to summarize the effect of either passive or active intermittent normobaric hypoxic interventions compared with normoxia on health-related outcomes in healthy older adults. METHODS: Relevant studies were searched from PubMed and Web of Science databases in accordance with PRISMA guidelines (since their inceptions up until August 9, 2022) using the following inclusion criteria: (1) randomized controlled trials, clinical trials and pilot studies; (2) Studies involving humans aged > 50 years old and without any chronic diseases diagnosed; (3) interventions based on in vivo intermittent systemic normobaric hypoxia exposure; (4) articles focusing on the analysis of health-related outcomes (body composition, metabolic, bone, cardiovascular, functional fitness or quality of life). Cochrane Collaboration recommendations were used to assess the risk of bias. RESULTS: From 509 articles initially found, 17 studies were included. All interventions were performed in moderate normobaric hypoxia, with three studies using passive exposure, and the others combining intermittent hypoxia with training protocols (i.e., using resistance-, whole body vibration- or aerobic-based exercise). CONCLUSIONS: Computed results indicate a limited effect of passive/active intermittent hypoxia (ranging 4-24 weeks, 2-4 days/week, 16-120 min/session, 13-16% of fraction of inspired oxygen or 75-85% of peripheral oxygen saturation) compared to similar intervention in normoxia on body composition, functional fitness, cardiovascular and bone health in healthy older (50-75 years old) adults. Only in specific settings (i.e., intermediate- or long-term interventions with high intensity/volume training sessions repeated at least 3 days per week), may intermittent hypoxia elicit beneficial effects. Further research is needed to determine the dose-response of passive/active intermittent hypoxia in the elderly. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2022 CRD42022338648.

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Exposure to acute normobaric hypoxia (NH) elicits reactive oxygen species (ROS) accumulation, whose production kinetics and oxidative damage were here investigated. Nine subjects were monitored while breathing an NH mixture (0.125 FIO2 in air, about 4100 m) and during recovery with room air. ROS production was assessed by Electron Paramagnetic Resonance in capillary blood. Total antioxidant capacity, lipid peroxidation (TBARS and 8-iso-PFG2α), protein oxidation (PC) and DNA oxidation (8-OH-dG) were measured in plasma and/or urine. The ROS production rate (µmol·min-1) was monitored (5, 15, 30, 60, 120, 240 and 300 min). A production peak (+50%) was reached at 4 h. The on-transient kinetics, exponentially fitted (t1/2 = 30 min r2 = 0.995), were ascribable to the low O2 tension transition and the mirror-like related SpO2 decrease: 15 min: -12%; 60 min: -18%. The exposure did not seem to affect the prooxidant/antioxidant balance. Significant increases in PC (+88%) and 8-OH-dG (+67%) at 4 h in TBARS (+33%) one hour after hypoxia offset were also observed. General malaise was described by most of the subjects. Under acute NH, ROS production and oxidative damage resulted in time and SpO2-dependent reversible phenomena. The experimental model could be suitable for evaluating the acclimatation level, a key element in the context of mountain rescues in relation to technical/medical workers who have not had enough time for acclimatization-as, for example, during helicopter flights.

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