Normobaric Hypoxia Research Articles

Cognitive performance during exposure to moderate normobaric hypoxia after sleep restriction: Relationship to physiological and stress biomarkers

IntroductionExposure to moderate levels of simulated hypoxia has subtle cognitive effects relative to ground level, in healthy individuals. However, there are few data on the cognitive consequences of the combination of hypoxia and partial sleep deprivation, which is a classic military or civilian operational context. In this study, we tested the hypothesis that exposure to moderate hypoxia while sleep-restricted impairs several domains of cognition, and we also assessed physiological parameters and salivary concentrations of cortisol and alpha-amylase. MethodSeventeen healthy males completed two sessions of cognitive tests (sustained attention using the PVT psychomotor vigilance task and executive functions using the Go-NoGo inhibition task and N-Back working memory task) after 30 min (T + 30′) and 4 h (T + 240′) of exposure in a normobaric hypoxic tent (FIO2 = 13.6 %, ≃ 3,500 m) (HY). This was completed after one night of sleep restriction (3 a.m. to 6 a.m. bedtime, SRHY) and one night of habitual sleep (10 p.m. to 6 a.m. bedtime, HSHY) (with cross-over randomization). The two nights sleep architecture and physiological parameters (oxygen saturation (SpO2) and heart rate (HR) during T + 30′ and T + 240′sessions were analyzed. Salivary cortisol and alpha-amylase (sAA) concentrations were analyzed before hypoxia, after the T + 30′ and T + 240′ cognitive sessions, and after leaving the hypoxic tent. ResultsSustained attention (RT and number of lapses in the PVT) and executive functions (Go-NoGo and 1-Back and 2-Back parameters, as inhibition and working memory signatures) were impaired in the SRHY condition compared to HSHY. SpO2 and HR were higher after 4 h compared with 30 min of hypoxia in the HSHY condition, while only HR was statistically higher in the SRHY condition. In SRHY, salivary AA concentration was lower and cortisol was higher than in HSHY. A significant increase in sAA concentration is observed after the cognitive session at 4 h of hypoxia exposure compared to that at 30 min, only in the SRHY condition. There are significant positive correlations between reaction time and the corresponding heart rate (a non-invasive marker of physiological stress) for the executive tasks in the two sleep conditions. This was not observed for salivary levels of sAA and cortisol, respective reliable indicators of the sympathoadrenomedullary system and the hypothalamic-pituitary adrenocortical system. ConclusionExposure to moderate normobaric hypoxia (≃ 3500 m / ≃ 11,500 ft simulated) after a single night of 3-hour sleep impairs cognitive performance after 30 min and 4 h of exposure. The key determinants and/or mechanism(s) responsible for cognitive impairment when exposed to moderate hypoxia with sleep restriction, particularly on the executive function, have yet to be elucidated.

Dose-response effects of caffeine during repeated cycling sprints in normobaric hypoxia to exhaustion.

With limited studies exploring the dose-response of caffeine consumption on repeated sprint ability in hypoxia, this study aimed to determine the optimal caffeine dose (low, moderate or high) during repeated sprints in hypoxia to exhaustion. On separate visits, twelve active males randomly performed four experimental trials in normobaric hypoxia (inspired oxygen fraction: 16.5 ± 0.2%). Participants ingested placebo (PLA) or caffeine capsules (3, 6 or 9mg/kg or LOW, MOD and HIGH, respectively) 1h before exercise and then underwent a repeated cycling sprint test (10s sprint/20s active recovery) to exhaustion. Total sprint number and work done, peak and mean power output, blood lactate concentration, cardiorespiratory and perceptual responses were recorded. Total sprint number was greater in MOD and HIGH compared to PLA (20 ± 7 and 18 ± 8 vs. 13 ± 4; all P < 0.05), with MOD also higher than LOW (15 ± 6; P = 0.02). Total work done was greater in MOD (111 ± 40kJ) and HIGH (100 ± 35kJ) compared to LOW (83 ± 29kJ) and PLA (76 ± 25kJ) (all P < 0.05). However, there were no significant differences in total sprint number or total work done between MOD and HIGH (all P > 0.05). Blood lactate concentration was higher in both MOD and HIGH compared to PLA (all P < 0.05). However, peak and mean power outputs, fatigue index, and ratings of perceived exertion did not differ across different caffeine dosages (all P > 0.05). A moderate dose of caffeine (6mg/kg) is the optimal amount for enhancing repeated cycling sprint ability when compared to low and high doses in moderate normobaric hypoxia.

The effects of four hours of normobaric hypoxia on the vestibular control of balance.

Whole-body vestibular-evoked balance responses decrease following ~ 55min of normobaric hypoxia. It is unclear how longer durations of hypoxia affect the vestibular control of balance at the muscle and whole-body levels. This study examined how four hours of normobaric hypoxia influenced the vestibular control of balance. Fifteen participants (4 females; 11 males) stood on a force plate with vision occluded and head rotated rightward while subjected to three blocks of binaural, bipolar stochastic electrical vestibular stimulation (EVS; 0-25Hz, root mean square amplitude = 1.1mA) consisting of two, 90-s trials. The relationship between EVS and anteroposterior (AP) forces or medial gastrocnemius (MG) electromyography (EMG) was estimated in the time and frequency domains at baseline (BL; 0.21 fraction of inspired oxygen-FIO2) and following two (H2) and four (H4) hours of normobaric hypoxia (0.11 FIO2). The EVS-MG EMG short-latency peak and peak-to-peak amplitudes were smaller than BL at H2 and H4, but the medium-latency peak amplitude was only lower at H4. The EVS-AP force medium-latency peak amplitude was lower than BL at H4, but the short-latency peak and peak-to-amplitudes were unchanged. The EVS-MG EMG coherence and gain were reduced compared to BL at H2 and H4 across multiple frequencies ≥ 7Hz, whereas EVS-AP force coherence was blunted at H4 (≤ 4Hz), but gain was unaffected. Overall, the central nervous system's response to vestibular-driven signals during quiet standing wasdecreased forup to four hours of normobaric hypoxia, and vestibular-evoked responses recorded within postural muscles may be more sensitive than the whole-body response.

The Effects of Normobaric Hypoxia on the Acute Physiological Responses to Resistance Training: A Narrative Review.

Allsopp, GL, Britto, FA, Wright, CR, and Deldicque, L. The effects of normobaric hypoxia on the acute physiological responses to resistance training: a narrative review. J Strength Cond Res XX(X): 000-000, 2024-Athletes have used altitude training for many years as a strategy to improve endurance performance. The use of resistance training in simulated altitude (normobaric hypoxia) is a growing strategy that aims to improve the hypertrophy and strength adaptations to training. An increasing breadth of research has characterized the acute physiological responses to resistance training in hypoxia, often with the goal to elucidate the mechanisms by which hypoxia may improve the training adaptations. There is currently no consensus on the overall effectiveness of hypoxic resistance training for strength and hypertrophy adaptations, nor the underlying biochemical pathways involved. There are, however, numerous interesting physiological responses that are amplified by performing resistance training in hypoxia. These include potential changes to the energy system contribution to exercise and alterations to the level of metabolic stress, hormone and cytokine production, autonomic regulation, and other hypoxia-induced cellular pathways. This review describes the foundational exercise physiology underpinning the acute responses to resistance training in normobaric hypoxia, potential applications to clinical populations, including training considerations for athletic populations. The review also presents a summary of the ideal training parameters to promote metabolic stress and associated training adaptations. There are currently many gaps in our understanding of the physiological responses to hypoxic resistance training, partly caused by the infancy of the research field and diversity of hypoxic and training parameters.

Perinatal hypoxia augments contractile impact of NADPH oxidase-derived ROS in early postnatal rat arteries.

Reactive oxygen species (ROS), including those produced by NADPH oxidase (NOX), play an important vasomotor role, especially at early postnatal period. Mechanisms for regulating vascular tone can change significantly due to neonatal asphyxia and accompanying hypoxia. We tested the hypothesis that normobaric hypoxia (8% O2) for 2 h at the second day of life changes the functional contribution of NOX-derived ROS to the regulation of agonist-induced contraction in early postnatal rats. We studied saphenous arteries from 11- to 14-day-old male offspring using isometric myography and Western blotting and assessed the content of biochemical parameters in blood serum. The values of main biochemical parameters in blood serum and the protein content of NOXs and superoxide dismutases in arterial tissue did not differ between "Control" and "Hypoxia" pups. The NOX inhibitor VAS2870 equally reduced the contractile responses of arteries to α1-adrenoceptor agonist methoxamine in "Control" and "Hypoxia" pups, but its effect was more pronounced in the arteries from "Hypoxia" pups when vasocontraction was evoked by the agonist of thromboxane A2 receptors U46619. Perinatal hypoxia at the second day of life increases procontractile influence of NOX-derived ROS to the regulation of U46619-induced vasocontraction in the systemic arteries at early postnatal ontogenesis. Nothing is known about programming effects of perinatal hypoxia, including birth asphyxia, on the ROS-mediated regulation of contraction in systemic arteries of early postnatal organism. 2-h normobaric hypoxia (8% O2) in rats at the second day of life increases the procontractile contribution of NOX-produced ROS to the regulation of U46619-induced vasocontraction in the systemic arteries at early postnatal ontogenesis. This fact may serve as a risk factor for the development of various disorders at later developmental stages and should be considered regarding the therapy for newborns who have suffered neonatal asphyxia.

The effects of real vs simulated high altitude on associative memory for emotional stimuli

IntroductionThis study aimed to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on associative memory performance for emotionally valenced stimuli. MethodsTwo experiments were conducted. In Study 1, n = 18 undergraduates performed an associative memory task under three NH conditions (FiO2= 20.9 %, 15.1 %, 13.6 %) using a tent with a hypoxic generator. In Study 2, n = 20 participants were assessed in a field study at various altitudes on the Himalayan mountains, including the Pyramid Laboratory (5000 m above sea level), using functional Near-Infrared Spectroscopy (fNIRS) and behavioral assessments. ResultsStudy 1 revealed no significant differences in recognition accuracy across NH conditions. However, Study 2 showed a complex relationship between altitude and memory for emotionally valenced stimuli. At lower altitudes, participants more accurately recognized emotional stimuli compared to neutral ones, a trend that reversed at higher altitudes. Brain oxygenation varied with altitude, indicating adaptive cognitive processing, as revealed by fNIRS measurements. ConclusionsThese findings suggest that hypoxia affects associative memory and emotional processing in an altitude-dependent manner, highlighting adaptive cognitive mechanisms. Understanding the effects of hypobaric hypoxia on cognition and memory can help develop strategies to mitigate its impact in high-altitude and hypoxic environments.

Nuclear factor of activated T-cells 5 is indispensable for a balanced adaptive transcriptional response of lung endothelial cells to hypoxia.

Chronic hypoxia causes detrimental structural alterations in the lung, which may cause pulmonary hypertension and are partially mediated by the endothelium. While its relevance for the development of hypoxia-associated lung diseases is well known, determinants controlling the initial adaptation of the lung endothelium to hypoxia remain largely unexplored. We revealed that hypoxia activates the transcription factor nuclear factor of activated T-cells 5 (NFAT5) and studied its regulatory function in murine lung endothelial cells (MLECs). EC-specific knockout of Nfat5 (Nfat5(EC)-/-) in mice exposed to normobaric hypoxia (10% O2) for 21 days promoted vascular fibrosis and aggravated the increase in pulmonary right ventricular systolic pressure as well as right ventricular dysfunction as compared with control mice. Microarray- and single-cell RNA-sequencing-based analyses revealed an impaired growth factor-, energy-, and protein-metabolism-associated gene expression in Nfat5-deficient MLEC after exposure to hypoxia for 7 days. Specifically, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb)-a hypoxia-inducible factor 1 alpha (HIF1α)-regulated driver of vascular smooth muscle cell (VSMC) growth-in capillary MLEC of hypoxia-exposed Nfat5(EC)-/- mice, which was accompanied by intensified VSMC coverage of distal pulmonary arteries. Collectively, our study shows that early and transient subpopulation-specific responses of MLEC to hypoxia may determine the degree of organ dysfunction in later stages. In this context, NFAT5 acts as a protective transcription factor required to rapidly adjust the endothelial transcriptome to cope with hypoxia. Specifically, NFAT5 restricts HIF1α-mediated Pdgfb expression and consequently limits muscularization and resistance of the pulmonary vasculature.

Arterial Oxygen Desaturation Hinders Gamified Working Memory Performance.

Hypoxia presents a physiological challenge to the Warfighters during military aviation and subterranean warfare operations by decreasing the supply of oxygen to the brain, which results in a reduced cognitive function depending on the magnitude and duration of hypoxic exposure. Moderate hypoxic exposures, fractions of inspired oxygen (FiO2) of 0.11 to 0.14, show no effects on simple tasks, but complex tasks like working memory may be hindered. Unfortunately, people often cannot recognize their own symptoms of hypoxemia, which are individualistic at moderate hypoxic exposure. Thus, screening tools, like gamified cognitive assessments, during moderate hypoxia may provide personnel objective feedback to initiate safety protocols before a possible accident. However, whether gamified assessments of working memory are sensitive to moderate hypoxia is unknown. Therefore, we tested the hypothesis which moderate normobaric hypoxia decreases gamified working memory performance when accounting for the individualistic responses of arterial blood oxygen saturations. Following 3 consecutive days of 2 practice sessions per day, 30 healthy adults (25 ± 5 years, 10 women) completed three 1-min rounds of the tablet-based working memory game (Backtracker, Statespace Labs, Inc.) at baseline and 60 and 90 min after exposure to FiO2 (= 0.138 ± 0.002 [hypoxia] and 0.201± 0.004 [normoxia] oxygen). Both conditions were completed on the same day and administered in a single-blind, block randomized manner. Arterial oxyhemoglobin saturation was estimated via forehead pulse oximetry (SpO2). Data were analyzed using linear mixed effects modeling. Compared to normoxia (99 ± 1%), SpO2 was lower (P < .001) at 60 (90 ± 2%) and 90 (90 ± 2%) min of hypoxia. A decrease in SpO2 was associated with a statistically significant decrease in the proportion of both tiles with the correct location (P < .02; -0.016) and correct order of appearance recalled (P < .01; -0.016). A decrease in SpO2 was associated with a statistically significant decrease in median time to first tap (P < .01; -0.041s) and median time between taps (P<.01; -0.030s). A significant interaction effect between the SpO2 decrease and baseline performance was found for proportion of tiles with the correct location recalled (P < .05; -0.014), median time to first tap (P <.01; -0.070s), and median time between taps (P < .01; -0.037s). A significant interaction effect between the SpO2 decrease and the path length was found for the proportion of tiles with the correct location recalled (P < .01; +0.021), median time to first tap (P < .01; -0.036s), and median time between taps (P < .01; -0.043s). These findings indicate that greater decreases in SpO2 during moderate hypoxic exposure hinder performance on a gamified assessment of working memory as measured by the proportion of correctly identified order and location of tiles. Considering the statistically significant decrease in both median time to first tap and median time between taps associated with the decrease in SpO2, participants are taking less time to plan or execute movements, which may compound or independently contribute to spatial and temporal memory mistakes.

Hemodynamics and cerebral oxygenation during acute exercise in moderate normobaric hypoxia and with concurrent cognitive task in young healthy males.

The present investigation aimed to study the cardiovascular responses and the cerebral oxygenation (Cox) during exercise in acute hypoxia and with contemporary mental stress. Fifteen physically active, healthy males (age 29.0±5.9 years) completed a cardiopulmonary test on a cycle ergometer to determine the workload at their gas exchange threshold (GET). On a separate day, participants performed two randomly assigned exercise tests pedaling for 6 min at a workload corresponding to 80% of the GET: (1) during normoxia (NORMO), and (2) during acute, normobaric hypoxia at 13.5% inspired oxygen (HYPO). During the last 3 min of the exercise, they also performed a mental task (MT). Hemodynamics were assessed with impedance cardiography, and peripheral arterial oxygen saturation and Cox were continuously measured by near-infrared spectroscopy. The main results were that both in NORMO and HYPO conditions, the MT caused a significant increase in the heart rate and ventricular filling rate. Moreover, MT significantly reduced (74.8±5.5vs. 62.0±5.2 A.U.) Cox, while the reaction time (RT) increased (813.3±110.2vs. 868.2±118.1ms) during the HYPO test without affecting the correctness of the answers. We conclude that in young, healthy males, adding an MT during mild intensity exercise in both normoxia and acute moderate (normobaric) hypoxia induces a similar hemodynamic response. However, MT and exercise in HYPO cause a decrease in Cox and an impairment in RT.

Caffeine has no effect on submaximal running in hypoxia in low caffeine consuming males and females.

Exposure to hypoxia immediately challenges a variety of physiologic systems that limit exercise capacity. Under normoxia, caffeine (CAFF) increases ventilation and subsequent oxygenation of hemoglobin (SpO<inf>2</inf>) and skeletal muscle (SmO<inf>2</inf>). CAFF improves exercise performance at altitude. However, little attention has been given to submaximal exercise in hypoxia, particularly regarding low CAFF consumers and female participants. The aim of this study was to determine the effect of CAFF on pulmonary, metabolic, and perceptual variables in response to submaximal running in hypoxia in low CAFF consuming males and females. In a double blinded, counterbalanced design, 14 (6 females) individuals (24.1±5.1 years; VO<inf>2max</inf>: 40.6±5.6 mL × kg-1 × min-1; 20.8±8.0% body fat), who habitually consumed ≤150 mg/day of CAFF performed treadmill running at workloads of 25%, 40%, 60%, and 75% of sea level VO<inf>2max</inf> in normobaric hypoxia (F<inf>I</inf>O<inf>2</inf>=0.15) on two separate occasions: 1) 60 minutes after 6 mg/kg of CAFF; or 2) placebo. CAFF had no effect on any variable measured. Specifically, V<inf>E</inf> (condition: P=0.12; interaction: P=0.19), V<inf>T</inf> (condition: P=0.16; interaction: P=0.57), and Ve:VO<inf>2</inf> (condition: P=0.07; interaction: P=0.69) were similar between groups. Further, CAFF had no effect on relative VO<inf>2</inf> (condition: P=0.84; interaction: P=0.95), HR (condition: P=0.28; interaction: P=0.35), SmO<inf>2</inf> (condition: P=0.66; interaction: P=0.82), or SpO<inf>2</inf> (condition: P=0.16; interaction: P=0.97). Finally, rating of perceived exertion (RPE; P=0.92) and acute mountain sickness scores (P=0.29) were similar across conditions. These data demonstrate that CAFF provides no physiologic advantage to submaximal exercise in acute, normobaric hypoxia with low CAFF consuming males and females.

Exercise responses to repeated cycle sprints with continuous and intermittent hypoxic exposure.

We examine the impact of the acute manipulation of oxygen availability during discrete phases (active and passive) of a repeated-sprint cycling protocol on performance, physiological, and perceptual responses. On separate days, twelve trained males completed four sets of five 5-s 'all out' cycle sprints (25-s inter-sprint recovery and 5-min interset rest) in four randomized conditions: normobaric hypoxia (inspired oxygen fraction of 12.9%) applied continuously (C-HYP), intermittently during only the sets of sprints (I-HYPSPRINT) or between-sets recovery periods (I-HYPRECOVERY), or not at all (C-NOR). Peak and mean power output, peripheral oxygen saturation, heart rate, blood lactate concentration, exercise-related sensations, and vastus lateralis muscle oxygenation using near-infrared spectroscopy were assessed. Peak and mean power output was ∼4%-5% lower for C-HYP compared to C-NOR (P≤0.050) and I-HYPRECOVERY (P≤0.027). Peripheral oxygen saturation was lower during C-HYP and I-HYPSPRINT compared with C-NOR and I-HYPRECOVERY during sets of sprints (∼83-85 vs. ∼95%-97%; P<0.001), while lower values were obtained for C-HYP and I-HYPRECOVERY than C-NOR and I-HYPSPRINT during between-sets rest period (∼84-85 vs. ∼96%; P<0.001). Difficulty in breathing was ∼21% higher for C-HYP than C-NOR (P=0.050). Ratings of perceived exertion (P=0.435), limb discomfort (P=0.416), heart rate (P=0.605), blood lactate concentration (P=0.976), and muscle oxygenation-derived variables (P=0.056 to 0.605) did not differ between conditions. In conclusion, the method of hypoxic exposure application (continuous vs. intermittent) affects mechanical performance, while internal demands remained essentially comparable during repeated cycle sprints.

Feasibility of Delivering 5-Day Normobaric Hypoxia Breathing in a Hospital Setting.

Beneficial effects of breathing at [Formula: see text] < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with [Formula: see text] as low as 0.11 in 5 healthy volunteers. All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from [Formula: see text] of 0.16 on the first day to [Formula: see text] of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' [Formula: see text], heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased [Formula: see text] and increased heart rate. At [Formula: see text] of 0.14, the mean [Formula: see text] was 92%; at [Formula: see text] of 0.13, the mean [Formula: see text] was 93%; at [Formula: see text] of 0.12, the mean [Formula: see text] was 88%; at [Formula: see text] of 0.11, the mean [Formula: see text] was 85%; and, finally, at an [Formula: see text] of 0.21, the mean [Formula: see text] was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. Results of the current physiologic study suggests that, within a hospital setting, delivering [Formula: see text] as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline.

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Hypoxia-Induced Pulmonary Injury-Adrenergic Blockade Attenuates Nitrosative Stress, and Proinflammatory Cytokines but Not Pulmonary Edema.

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.

Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.

Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol

BackgroundParkinson’s disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD.Methods/Design: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction.DiscussionThis trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD.Trial registrationClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

Prefrontal cortex oxygenation during a mentally fatiguing task in normoxia and hypoxia

Mental fatigue (MF) and hypoxia impair cognitive performance through changes in brain hemodynamics. We want to elucidate the role of prefrontal cortex (PFC)-oxygenation in MF. Twelve participants (22.9 ± 3.5 years) completed four experimental trials, (1) MF in (normobaric) hypoxia (MF_HYP) (3.800 m; 13.5%O2), (2) MF in normoxia (MF_NOR) (98 m; 21.0%O2), (3) Control task in HYP (CON_HYP), (4) Control in NOR (CON_NOR). Participants performed a 2-back task, Digit Symbol Substitution test and Psychomotor Vigilance task before and after a 60-min Stroop task or an emotionally neutral documentary. Brain oxygenation was measured through functional Near Infrared Spectroscopy. Subjective feelings of MF and physiological measures (heart rate, oxygen saturation, blood glucose and hemoglobin) were recorded. The Stroop task resulted in increased subjective feelings of MF compared to watching the documentary. 2-back accuracy was lower post task compared to pre task in MF_NOR and CON_NOR, while no differences were found in the other cognitive tasks. The fraction of inspired oxygen did not impact feelings of MF. Although performing the Stroop resulted in higher subjective feelings of MF, hypoxia had no effect on the severity of self-reported MF. Additionally, this study could not provide evidence for a role of oxygenation of the PFC in the build-up of MF.

Body Composition and Aerobic Performance Changes After 8 Weeks of Exposure to Normobaric Intermittent Hypoxia

Body Composition and Aerobic Performance Changes After 8 Weeks of Exposure to Normobaric Intermittent Hypoxia

Analysis of Muscle Oxygenation after a Normobaric Hypoxia Tolerance Test.

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.

Effect of Step Load Based on Time under Tension in Hypoxia on the ACL Pre-Operative Rehabilitation and Hormone Levels: A Case Study.

The aim of the study was to determine the effect of step load in hypoxia on the effectiveness of preoperative rehabilitation (PR) and hormone levels based on a case study. Introduction: We assessed the impact of variables such as rate of movement and time under tension (TUT) in normobaric hypoxia on the levels of growth hormone (GH), insulin-like growth factor 1 (IGF-1), and erythropoietin (EPO). Additionally, the impact of step load on the hypertrophy and strength of knee extensors and flexors was assessed. Methods: The work uses a case study, the research subject of which was a 23-year-old female professional handball player. The tests included an isokinetic assessment of the peak torque of knee extensors and flexors as well as body composition analysis. Results: The results showed a more than (10.81-fold) increase in GH after the microcycle with time under tension (TUT). The deficit between the lower limbs was also reduced. Conclusions: Using a hypoxic environment based on an appropriate altitude, combined with changes such as a short rest break between sets and a controlled tempo of movement with an eccentric phase, TUT may offer an alternative to the PR process, especially among athletes who care about fast RTS.