Moderate Hypoxia Research Articles

Intermittent hypoxia training improves cerebral blood flow without cognitive impairment.

Brief exposure to intermittent hypoxia has been shown to potentially induce protective effects in the body. Animal studies suggest that intermittent hypoxia could increase cerebral blood flow and confer resistance to subsequent hypoxic-ischemic injury, yet clinical investigations are limited. This study aimed to evaluate the impact of a moderate short-term intermittent hypoxia protocol on cerebral blood flow and cognitive performance. Subjects who met the inclusion criteria were recruited to this study and randomized into the intermittent hypoxia group or the control group, which receives intermittent hypoxia training and sham-intermittent hypoxia training, respectively. Cerebral hemodynamics, cognitive performance, cerebral perfusion pressure, and oxygen saturation were assessed before and after the intervention. A total of 100 healthy participants were included in this study. Compared to the control group, the intermittent hypoxia group exhibited higher peak systolic blood flow velocity (108.64 ± 22.53 vs. 100.21 ± 19.06, p = 0.049) and cerebrovascular conduction index (0.74 ± 0.17 vs. 0.66 ± 0.21, p = 0.027), and lower cerebrovascular resistance index (1.41 ± 0.29 vs. 1.54 ± 0.36, p = 0.044) following intermittent hypoxia training. Additionally, within-group comparisons revealed that intermittent hypoxia training led to increased cerebral blood flow velocity, elevated cerebrovascular conductance index, and decreased cerebrovascular resistance index (p < 0.05). Other indicators including cognitive function, cerebral perfusion pressure, and oxygen saturation did not exhibit significant differences between groups. These findings revealed that intermittent hypoxia may represent a safe and effective strategy for improving cerebral blood flow.

Fipronil exposure alters oxidative stress responses of Nile tilapia (Oreochromis niloticus) to acute moderate hypoxia

Acute hypoxia is known to increase the generation of reactive oxygen species (ROS), leading to modulation in antioxidant defenses. Pollutant exposure can potentiate ROS generation during hypoxic events and impair antioxidant defenses, increasing the susceptibility of hypoxia-tolerant fishes, such as the Nile tilapia (Oreochromis niloticus), to oxidative stress. The purpose of this study was to evaluate oxidative stress responses of O. niloticus to acute (3 and 8 h) moderate hypoxia (dissolved oxygen ≤2 mg/L−1) and how these responses are affected by simultaneous exposure to the insecticide fipronil (0.1 and 0.5 µg L−1). Hypoxia exposure for 3 h caused an increase in glutathione peroxidase (GPx) activity in the gill and also increased catalase (CAT) and glutathione S-transferase (GST) activities in the liver. After 8 h of hypoxia, glutathione reductase (GR) activity increased. DNA damage (comet assay) in erythrocytes was reduced by hypoxia after 3 and 8 h. Fipronil exposure for 3 h decreased CAT activity in the gill, both under normoxia and hypoxia. After 8h, the combination of fipronil and hypoxia increased GR activity in the gill. In the liver, fipronil exposure under hypoxia for 3 h increased CAT and GR activities; after 8 h, CAT was decreased, and GST increased. GR was also increased by fipronil under normoxia for 8 h. All treatments reduced lipid peroxidation levels in the gills, but in the liver, lipid peroxidation was increased by fipronil after 3 h under normoxia. Moreover, fipronil exposure under hypoxia for 3 and 8h increased DNA damage in erythrocytes, while 8 h of fipronil exposure under normoxia decreased it, suggesting the activation of DNA repair mechanisms. Results show that both fipronil and hypoxia exposure significantly modulate the oxidative stress parameters of O. niloticus and that the combination of these factors produces more pronounced effects.

Preconditioning with Moderate Hypoxia Increases Tolerance to Subsequent Severe Hypoxia in Rats with LPS-Induced Endotoxemia

Hyperproduction of mediators of LPS-induced inflammatory process (endotoxicosis, sepsis) initiates the development of acute respiratory failure (ARF), impaired gas exchange, progressive hypoxemia and hypercapnia, hypotension, respiratory arrest and death. Severe sepsis associated with hypoxemia remains the main cause of death, and therefore the development of methods to increase resistance to acute hypoxia in septic patients is an urgent task. The aim of the work was to study the effectiveness of preconditioning with short-term intermittent moderate hypoxia to increase tolerance to subsequent severe hypoxia in rats with LPS-induced endotoxicosis. The experiments were carried out on anesthetized and tracheostomated male Wistar rats. Endotoxicosis was modeled by administration of a lipopolysaccharide solution (Escherichia coli) in an amount of 7 mg/kg. To assess resistance to severe hypoxia, the rebreathing method of (RM) with a gradual decrease in oxygen in the rebreather from 21% to the onset of apnea was used. Hypoxic preconditioning (hypoxic training, HT) was also created by the method of RM in the mode of 3 cycles: reduction of the oxygen fraction in the rebreather to 12% – 3 min, 5 min – normoxia. 3 groups of animals were studied: I-control-NaCl, II–LPS, III–LPS+HT. The following parameters were recorded: external respiration, mean blood pressure (APm.), saturation (SpO2), fraction of inhaled O2, time of onset of apnea, the amount of spontaneous respiratory recovery (autoresuscitation) in the posthypoxic period. It was shown that the administration of LPS under normoxic conditions was accompanied by hyperventilation, hypoxemia and hypotension. The maximum deterioration in resistance to severe hypoxia was observed in rats with LPS, which was manifested by a decrease in APm, SpO2 and a decrease in the possibility of autoresuscitation after hypoxic apnea. The effect of HT prevented a decrease in blood pressure, SpO2 increased by 1.4 times, survival increased by 2 times, which is comparable to the level of normoxia before the introduction of LPS. It is assumed that the effectiveness of hypoxic preconditioning is due to the inhibition of the inflammatory response.

Changes in reactive oxygen species and autofluorescence under hypoxia at the hippocampal CA3 area: Role of calcium and zinc influxes

Reactive oxygen species (ROS) have an important role in cellular biology, being involved, in a way that depends on their levels, in cell signaling processes or in oxidative stress, probably associated with neurodegenerative and other diseases. Most of the studies about ROS formation were performed in ischemic conditions, and thus, there is limited knowledge about ROS formation in less severe hypoxic conditions. This study investigates neuronal ROS generation and autofluorescence changes in hypoxic conditions, focusing on the involvement of calcium and zinc. Using hippocampal slices from Wistar rats, ROS production was monitored by the permeant fluorescent indicator H2DCFDA under different oxygenation levels. Moderate hypoxia (40% O2) led to a small ROS increase, while severe hypoxia (0% O2) showed a more pronounced rise. KCl-induced depolarization significantly enhanced ROS formation, particularly under severe hypoxia. Inhibition of NMDA receptors reduced ROS generation without affecting autofluorescence, while chelation of zinc ions decreased ROS production and increased flavin adenine dinucleotide (FAD) autofluorescence. These findings suggest that, in hypoxic conditions, ROS formation is mediated by calcium entry through NMDA receptors and also by zinc influxes. Thus, these ions play a crucial role in oxidative stress, which may be related with neurodegenerative diseases associated with ROS dysregulation.

Is it Possible for Individuals with Pre-Existing Mental Disorders to Perform Mountain Sports at High Altitude-First Evidence from a Pilot Cross-Sectional Questionnaire Study.

Gstir, Claudia, Timo Schurr, Roxana Ehlers, Johannes Burtscher, Barbara Sperner-Unterweger, and Katharina Hüfner. Is it possible for individuals with pre-existing mental disorders to perform mountain sports at high altitude-First evidence from a pilot cross-sectional questionnaire study. High Alt Med Biol. 00:00-00, 2024. Introduction: Mountain sports at high altitude (HA) are gaining increasing popularity, but little is known about the effect of such activities on mental health, despite a great prevalence of mental disorders. Methods: Data were collected using an online self-report questionnaire assessing mental and somatic disorders in individuals performing mountain sports at HA (>2,500 m above sea level [ASL]) as well as their symptom change. Nonparametric tests were used for analyses. Results: 251 individuals without pre-existing disorders (noD), 34 with somatic disorders (somaD), and 38 with mental disorders (mentalD; mainly depressive, eating, and anxiety disorders) participated in this study. Overall, 44.7% of the mentalD group compared with 14.7% of somaD experienced ameliorated symptoms during mountain sports at HA, while 2.6% and 8.8%, respectively, reported a worsening (χ2[2] =8.13, p = 0.017). People in the mentalD compared with somaD group significantly less frequently inform tour partners (41.9% vs. 90.9%; χ2[2]=16.69, p < 0.001) about their condition or consult their physician (2.6% vs. 26.5%; χ2[1]=8.53, p = 0.003) regarding their plans to perform mountain sports at HA. 14.5% of all participants reported mental symptoms at 2,500-3,500 m ASL, 23.5% between >3,500-5,500 m ASL and 31.8% >5,500 m ASL. Conclusion: Individuals with mental disorders often report improved mental health during mountain sports at HA, possibly due to a combination of physical activity, the alpine natural environment, and/or moderate hypoxia. The fact that tour partners and physicians are rarely informed shows the need to reduce the stigma of mental disorders in the mountain sports community. The study was prospectively registered with the German Clinical Trials Registry (DRKS00024949).

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.

Physiological parameters and training characteristics of endurance runners at Ethiopian Youth Sports Academy (2400 meters above sea level) and Guna Athletics Sport Club (3100 meters above sea level) training camps: a comparative cross-sectional study.

Endurance performance is impacted by physiological, anthropometrical, diet, genetic, psychological, and training characteristics. Altitude can affect physiological parameters (like maximum oxygen utilization, arterial oxygen saturation (SaO<inf>2</inf>), heart rate, and blood pressure) and training characteristics (duration, frequency, and training load). Thus, this study compared physiological parameters and training characteristics between endurance runners at Ethiopian Youth Sports Academy (EYSA) and Guna Athletics Sport Club (GASC) located which are located at elevation of 2400 and 3100 meters, respectively. A comparative cross-sectional study design was used from September to November 2021. Data was obtained from a total of 120 eligible participants (30 runners and 30 controls at GASC, and 30 runners and 30 controls at EYSA). Sociodemographic and training characteristics were assessed using self-administered standardized questionnaires. SaO<inf>2</inf> and heart rate were measured using finger pulse-oximetry (Nellcor, Oxim N-65; Covidien, Dublin, Ireland). Blood pressure was measured by Folee Digital Blood Pressure Monitor DX-B1 (Jiangsu Folee Medical Equipment Co., Ltd., Zhenjiang, China). The runners of GASC had significantly lower resting SaO<inf>2</inf>, SaO<inf>2</inf> immediately after maximal exertion, training (frequency and load) than runners of EYSA in both sexes. Runners of Guna Athletics Sport Club (RGASC) had significantly higher maximum oxygen utilization (VO<inf>2</inf>max) than Runners Ethiopian Youth Sports Academy (REYSA) in both sexes. Severe exercise-induced hypoxemia (EIAH) and moderate EIAH were developed by male runners of GASC and EYSA respectively. Besides, female runners GASC and EYSA developed moderate and mild EIAH, respectively. Conclusively, there were significant differences in physiological parameters and training load between RGASC and REYSA. High altitude (3100 meters) may have a greater impact on the above variables than moderate hypoxia (2400 meters above sea level). Hence, endurance runner coaches should give emphasis to these variables.

Effect of Moderate and Acute Hypoxia on the Antioxidant Enzyme Complex of the Tissues of the Black Sea Mussel Mytilus galloprovincialis

Effect of Moderate and Acute Hypoxia on the Antioxidant Enzyme Complex of the Tissues of the Black Sea Mussel Mytilus galloprovincialis

Synergy of exercise and hypoxia for brain health and aging – A narrative review

Regular exercise is a well-established means to improve brain health and prevent age-related neurological diseases, including dementia (Marques-Aleixo et al., 2020). The precise mechanisms how direct exercise effects are transmitted to the brain remain incompletely understood. However, the increased oxygen demand and associated metabolic stress in the primarily affected tissues – the working skeletal muscle, the cardiovascular and the respiratory system – likely play crucial roles in exercise-signalling to the brain (Severinsen &amp; Pedersen, 2020). Besides the mobilization of beneficial circulating factors, the modulation of blood properties and blood-flow, the immune system and the autonomous system are involved. Intriguingly, physiological stress induced by low environmental oxygen availability (hypoxia) can induce the activation of similar processes like exercise. The aim of this contribution is to evaluate the role of hypoxia in the benefits of exercise on the brain. Accumulating evidence demonstrates the potential of direct modulation of inspired oxygen levels to improve neurological diseases (Burtscher et al., 2021). Reduced all-cause mortality in people living at moderate altitudes (and therefore in chronic, mild hypobaric hypoxia) may also be associated with reduced risk of neurological diseases, including of stroke (Faeh et al., 2009). This is surprising, because the hypoxic stress at moderate altitudes (usually defined as altitudes between 1,500 and 2,500 m) is generally considered too low to induce substantial hypoxia adaptations. It is thus possible that the combination of moderate environmental hypoxia at moderate altitude with the increased oxygen demand during exercise is required to promote protective adaptations, such as of the brain. Considering this possibility, synergistic and complementary molecular and systemic responses and adaptations to exercise and hypoxia may benefit the brain. Among the involved molecular processes are mitochondrial changes following cellular stress that are also linked to the regulation of adaptations by the transcription factor hypoxia inducible factor, which is activated by both hypoxia and exercise. Mitochondria are the main molecular oxygen consumers, respond sensitively to stress and dispose of a wide array of intra- and intercellular communication modes (Memme et al., 2021). Moreover, exerkines, blood-borne factors released in response to exercise, have emerged as important mediators of inter-organ exercise-signalling (Severinsen &amp; Pedersen, 2020) and modulate the autonomic and immune system in response to hypoxic and metabolic stress. In conclusion, the activation of endogenous responses to hypoxic and metabolic stress are powerful means to improve brain health and healthy aging. Based on the overlapping and distinct physiological responses to hypoxia and exercise, brain benefits of exercising at higher altitudes and advances in the development of customized strategies to improve brain resilience are promising approaches to target neurological diseases. While the safe performance of exercise in moderate altitudes is already considered an impactful way to improve brain health, the optimization of combined exercise and (artificially induced) hypoxia for specific target groups requires further in-depth investigation. References Burtscher, J., Mallet, R. T., Burtscher, M., &amp; Millet, G. P. (2021). Hypoxia and brain aging: Neurodegeneration or neuroprotection? Ageing Research Reviews, 68, Article 101343. https://doi.org/10.1016/j.arr.2021.101343 Faeh, D., Gutzwiller, F., Bopp, M., &amp; Group, S. N. C. S. (2009). Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation, 120(6), 495-501. https://doi.org/10.1161/CIRCULATIONAHA.108.819250 Marques-Aleixo, I., Beleza, J., Sampaio, A., Stevanović, J., Coxito, P., Gonçalves, I., Ascensão, A., &amp; Magalhães, J. (2020). Preventive and therapeutic potential of physical exercise in neurodegenerative diseases. Antioxidants &amp; Redox Signaling, 34(8), 674–693. https://doi.org/10.1089/ars.2020.8075 Memme, J. M., Erlich, A. T., Phukan, G., &amp; Hood, D. A. (2021). Exercise and mitochondrial health. The Journal of Physiology, 599(3), 803-817. https://doi.org/10.1113/jp278853 Severinsen, M. C. K., &amp; Pedersen, B. K. (2020). Muscle-organ crosstalk: The emerging roles of myokines. Endocrine Reviews, 41(4), 594-609. https://doi.org/10.1210/endrev/bnaa016

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.

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.

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.

Changes in gill neuroepithelial cells and morphology of threespine stickleback (Gasterosteus aculeatus) to hypoxia and simulated ocean acidification.

Coastal marine environments are characterized by daily, seasonal and long-term changes in both O2 and CO2, driven by local biotic and abiotic factors. The neuroepithelial cells (NECs) of fish are thought to be the putative chemoreceptors for sensing oxygen and CO2, and, thus, NECs play a key role in detecting these environmental changes. However, the role of NECs as chemosensors in marine fish remains largely understudied. In this study, the NECs of marine threespine sticklebacks (Gasterosteus aculeatus) were characterized using immunohistochemistry. We then determined if there were changes in NEC size and density, and in gill morphology in response to either mild (10kPa) or moderate (6.8kPa) hypoxia and two levels of elevated CO2 (1,500 and 3,000 µatm). We found that the NECs of stickleback contained synaptic vesicles and were innervated, and were 50-300% larger and 2 to 4 times more abundant than in other similar sized freshwater fishes. NEC size and density were largely unaffected by exposure to hypoxia, but there was a 50% decrease in interlamellar cell mass (ILCM) in response to mild and moderate hypoxia. NECs increased in size, but not abundance in response to elevated CO2. Moreover, fish exposed to moderate or elevated CO2 had 53-78% larger ILCMs compared to control fish. Our results demonstrated that adult marine sticklebacks have NECs that can respond to environmentally relevant pCO2 and likely hypoxia, which highlights the importance of NECs in marine fishes under the heterogeneity of environmental conditions in coastal areas.

CDK5RAP3 Inhibition by Hypoxia Activates P38MAPK to Facilitate Angiogenesis.

CDK5RAP3 is a recognized tumor suppressor that inhibits Chk1 and Chk2 and activates p53, all of which are involved with mediating toxin-induced apoptosis of cancer cells. CDK5RAP3 also inhibits p38MAPK phosphorylation and activity via mediating a p38 interaction with wild-type p53-induced phosphatase 1. This study aimed to investigate the antiangiogenic activity of CDK5RAP3 and its molecular mechanisms in human umbilical vein endothelial cells (HUVECs) under conditions of hypoxic conditions. Angiogenesis was induced in HUVECs mainly by vascular endothelial growth factor (VEGF). The CDK5RAP3 levels of HUVECs were reduced in a time-dependent manner in response to hypoxic treatment at 2% O2. The reduction of CDK5RAP3 was accompanied with increased p38MAPK phosphorylation and activation. Moderate hypoxia was found to significantly increase secreted VEGF concentrations, and the hypoxic conditioned medium (HCM) markedly enhanced proliferation, migration, and tube formation. Our findings indicate that moderate hypoxia facilitates angiogenesis by inhibiting CDK5RAP3. CDK5RAP3 exhibits a clear regulatory role in vascular regeneration, as downregulating its expression in endothelial cells enhances VEGF synthesis and subsequently improves cell migration and lumen formation capability. This study presents evidence indicating that moderate hypoxia facilitates angiogenesis by inhibiting CDK5RAP3, demonstrating the potential for CKD5RAP3 to be a potent antiangiogenic agent in angiogenesis regulation of cancer, ischemic diseases, and wound healing.

Combined Effects of Moderate Hypoxia and Sleep Restriction on Mental Workload.

Aircraft pilots face a high mental workload (MW) under environmental constraints induced by high altitude and sometimes sleep restriction (SR). Our aim was to assess the combined effects of hypoxia and sleep restriction on cognitive and physiological responses to different MW levels using the Multi-Attribute Test Battery (MATB)-II with an additional auditory Oddball-like task. Seventeen healthy subjects were subjected in random order to three 12-min periods of increased MW level (low, medium, and high): sleep restriction (SR, <3 h of total sleep time (TST)) vs. habitual sleep (HS, >6 h TST), hypoxia (HY, 2 h, FIO2 = 13.6%, ~3500 m vs. normoxia, NO, FIO2 = 21%). Following each MW level, participants completed the NASA-TLX subjective MW scale. Increasing MW decreases performance on the MATB-II Tracking task (p = 0.001, MW difficulty main effect) and increases NASA-TLX (p = 0.001). In the combined HY/SR condition, MATB-II performance was lower, and the NASA-TLX score was higher compared with the NO/HS condition, while no effect of hypoxia alone was observed. In the accuracy of the auditory task, there is a significant interaction between hypoxia and MW difficulty (F(2-176) = 3.14, p = 0.04), with lower values at high MW under hypoxic conditions. Breathing rate, pupil size, and amplitude of pupil dilation response (PDR) to auditory stimuli are associated with increased MW. These parameters are the best predictors of increased MW, independently of physiological constraints. Adding ECG, SpO2, or electrodermal conductance does not improve model performance. In conclusion, hypoxia and sleep restriction have an additive effect on MW. Physiological and electrophysiological responses must be taken into account when designing a MW predictive model and cross-validation.

Carryover effects of embryonic hypoxia exposure on adult fitness of the Pacific abalone

The widespread and severe drop in dissolved oxygen concentration in the open ocean and coastal waters has attracted much attention, but assessments of the impacts of environmental hypoxia on aquatic organisms have focused primarily on responses to current exposure. Past stress exposure might also affect the performance of aquatic organisms through carryover effects, and whether these effects scale from positive to negative based on exposure degree is unknown. We investigated the carryover effects of varying embryonic hypoxia levels (mediate hypoxia: 3.0−3.1 mg O2/L; severe hypoxia: 2.0−2.1 mg O2/L) on the fitness traits of adult Pacific abalone (Haliotis discus hannai), including growth, hypoxia tolerance, oxygen consumption, ammonia excretion rate, and biochemical responses to acute hypoxia. Moderate embryonic hypoxia exposure significantly improved the hypoxia tolerance of adult Pacific abalone without sacrificing growth and survival. Adult abalone exposed to embryonic hypoxia exhibited physiological plasticity, including decreased oxygen consumption rates under environmental stress, increased basal methylation levels, and a more active response to acute hypoxia, which might support their higher hypoxia tolerance. Thus, moderate oxygen declines in early life have persistent effects on the fitness of abalone even two years later, further affecting population dynamics. The results suggested that incorporating the carryover effects of embryonic hypoxia exposure into genetic breeding programs would be an important step toward rapidly improving the hypoxia tolerance of aquatic animals. The study also inspires the protection of endangered wild animals and other vulnerable species under global climate change.

Exposure to Various Degrees and Durations of Hypobaric Hypoxia Causes a Reduction in Body Weight of Female Adult Rats.

Hypobaric hypoxia refers to a condition where there is a decreased oxygen partial pressure in the air due to low atmospheric pressure. It is known to affect the metabolism, leading to increased basal metabolic rate, alterations in appetite, and changes in cellular metabolism and energy homeostasis. The effects of hypoxia on metabolism and weight loss are influenced by genetic factors, gender, and the duration and severity of exposure to hypoxia. Currently, there are no reports which elucidate the impact of hypobaric hypoxia on female laboratory rats. The aim of this study was to observe the effect of varying degrees and durations of hypobaric hypoxia on the body weight of female rats. In this study, the body weight of 36 laboratory rats divided into six groups was taken at day 0, and then, the rats were exposed to hypobaric hypoxia in a specially designed hypoxia chamber and their body weights were recorded after 5 days and 10 days of hypoxia exposure. The change in body weight at 5 days and 10 days was compared to that of their body weight before the exposure to hypoxia. Data analysis was performed using IBM SPSS version 20. Body weight was reduced in all rats subjected to varying degrees and duration of hypoxia. The percentage change in body weight was higher in moderate and severe hypoxia than in the mild hypoxia group. No significant difference was observed in rats exposed to varying degrees of hypoxia for 5 days as compared to those exposed for 10 days. Hypoxia may cause a reduction in body weight of female rats proportionate to the increasing severity of hypoxia and this reduction remains independent of the duration of exposure to hypoxia.

The vulnerability of sharks, skates, and rays to ocean deoxygenation: Physiological mechanisms, behavioral responses, and ecological impacts.

Levels of dissolved oxygen in open ocean and coastal waters are decreasing (ocean deoxygenation), with poorly understood effects on marine megafauna. All of the more than 1000 species of elasmobranchs (sharks, skates, and rays) are obligate water breathers, with a variety of life-history strategies and oxygen requirements. This review demonstrates that although many elasmobranchs typically avoid hypoxic water, they also appear capable of withstanding mild to moderate hypoxia with changes in activity, ventilatory responses, alterations to circulatory and hematological parameters, and morphological alterations to gill structures. However, such strategies may be insufficient to withstand severe, progressive, or prolonged hypoxia or anoxia where anaerobic metabolic pathways may be used for limited periods. As water temperatures increase with climate warming, ectothermic elasmobranchs will exhibit elevated metabolic rates and are likely to be less able to tolerate the effects of even mild hypoxia associated with deoxygenation. As a result, sustained hypoxic conditions in warmer coastal or surface-pelagic waters are likely to lead to shifts in elasmobranch distributions. Mass mortalities of elasmobranchs linked directly to deoxygenation have only rarely been observed but are likely underreported. One key concern is how reductions in habitat volume as a result of expanding hypoxia resulting from deoxygenation will influence interactions between elasmobranchs and industrial fisheries. Catch per unit of effort of threatened pelagic sharks by longline fisheries, for instance, has been shown to be higher above oxygen minimum zones compared to adjacent, normoxic regions, and attributed to vertical habitat compression of sharks overlapping with increased fishing effort. How a compound stressor such as marine heatwaves alters vulnerability to deoxygenation remains an open question. With over a third of elasmobranch species listed as endangered, a priority for conservation and management now lies in understanding and mitigating ocean deoxygenation effects in addition to population declines already occurring from overfishing.