Hypoxic Exercise Research Articles

Mitochondrial Proteins Unveil the Mechanism by Which Physical Exercise Ameliorates Memory, Learning and Motor Activity in Hypoxic Ischemic Encephalopathy Rat Model.

Background: Physical exercise has been shown to improve cognitive and motor functions, promoting neurogenesis and demonstrating therapeutic benefits in neurodegenerative disorders. Nonetheless, it is crucial to investigate the cellular and molecular mechanisms by which this occurs. The study aimed to investigate and evaluate the effect of swimming exercise on the changes of mitochondrial proteins in the brains of rats with hypoxic ischemic encephalopathy (HIE). Methods: the vertical pole and Morris water maze tests were used to assess the animals’ motor and cognitive functions, and western blot and immunofluorescence of brain tissue were used to assess the biomarkers of mitochondrial apoptosis and cristae stability in response to exercise training. Four groups of rats were used: (1) sham sedentary group (SHAM, NT), (2) sham exercise training group (SHAM, T) (3) hypoxic ischemic encephalopathy sedentary group (HIE, NT), and (4) hypoxic ischemic encephalopathy exercise training group (HIE, T). Results: animals with HIE showed motor and cognitive deficits, as well as increased apoptotic protein expression. Exercise, on the other hand, improved motor and cognitive functions while also suppressing the expression of apoptotic proteins. Conclusions: By stabilizing the mitochondrial cristae and suppressing the apoptotic cascade, physical exercise provided neuroprotection in hypoxic ischemia-induced brain injury.

Acute Exercise with Moderate Hypoxia Reduces Arterial Oxygen Saturation and Cerebral Oxygenation without Affecting Hemodynamics in Physically Active Males.

Hemodynamic changes during exercise in acute hypoxia (AH) have not been completely elucidated. The present study aimed to investigate hemodynamics during an acute bout of mild, dynamic exercise during moderate normobaric AH. Twenty-two physically active, healthy males (average age; range 23–40 years) completed a cardiopulmonary test on a cycle ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise tests (three minutes pedaling at 30% of Wmax): (1) during normoxia (NORMO), and (2) during normobaric AH at 13.5% inspired oxygen (HYPO). Hemodynamics were assessed with impedance cardiography, and peripheral arterial oxygen saturation (SatO2) and cerebral oxygenation (Cox) were measured by near-infrared spectroscopy. Hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial blood pressure, ventricular emptying rate, and ventricular filling rate) were not any different between NORMO and HYPO. However, the HYPO test significantly reduced both SatO2 (96.6 ± 3.3 vs. 83.0 ± 4.5%) and Cox (71.0 ± 6.6 vs. 62.8 ± 7.4 A.U.) when compared to the NORMO test. We conclude that an acute bout of mild exercise during acute moderate normobaric hypoxia does not induce significant changes in hemodynamics, although it can cause significant reductions in SatO2 and Cox.

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress.

What is the central question of this study? What is the effect of hypobaric hypoxia on markers of exercise-induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance? Exercise performed at 4300m of simulated altitude increased intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise-induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I-FABP, LBP and CLDN-3 were correlated to exercise-induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585m (NORM) and one at 4300m of simulated hypobaric hypoxia (HYP). Participants performed 60min of cycling at a workload that elicited 65% of their NORM . GI symptoms were assessed before and every 15min during exercise. Pre- and post-exercise blood samples were assessed for intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I-FABP significantly increased from pre- to post-exercise in HYP (708±191 to 1215±518pgml-1 ; P=0.011, d=1.10) but not NORM (759±224 to 828±288pgml-1 ; P>0.99, d=0.27). CLDN-3 significantly increased from pre- to post-exercise in HYP (13.8±0.9 to 15.3±1.2ngml-1 ; P=0.003, d=1.19) but not NORM (13.7±1.8 to 14.2±1.6ngml-1 ; P=0.435, d=0.45). LBP significantly increased from pre- to post-exercise in HYP (10.8±1.2 to 13.9±2.8μgml-1 ; P=0.006, d=1.12) but not NORM (11.3±1.1 to 11.7±0.9μgml-1 ; P>0.99, d=0.32). I-FABP (d=0.85), CLDN-3 (d=0.95) and LBP (d=0.69) were all significantly higher post-exercise in HYP compared to NORM (P≤0.05). Overall GI discomfort was significantly correlated to ΔI-FABP (r=0.71), ΔCLDN-3 (r=0.70) and ΔLBP (r=0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

Contribution of Hypoxic Exercise Testing to Predict High-Altitude Pathology: A Systematic Review.

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help predict altitude sickness. The purpose of this review is to evaluate the contribution of hypoxic exercise testing, achieved in normobaric conditions, in the prediction of severe high-altitude pathology. We performed a systematic review using the databases PubMed, Science Direct and Embase in October 2021 to collect studies reporting physiological adaptations under hypoxic exercise testing and its interest in predicting high-altitude pathology. Eight studies were eligible, concerning 3558 patients with a mean age of 46.9 years old, and a simulated mean altitude reaching of 5092 m. 597 patients presented an acute mountain sickness during their altitude travels. Three different protocols of hypoxic exercise testing were used. Acute mountain sickness was defined using Hackett’s score or the Lake Louise score. Ventilatory and cardiac responses to hypoxia, desaturation in hypoxia, cerebral oxygenation, core temperature, variation in body mass index and some perceived sensations were the highlighted variables associated with acute mountain sickness. A decision algorithm based on hypoxic exercise tests was proposed by one team. Hypoxic exercise testing provides promising information to help predict altitude complications. Its interest should be confirmed by different teams.

Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-β-hexosaminidase, ↑ β-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min—normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min—hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

Repeated sprint exercise in hypoxia stimulates HIF-1-dependent gene expression in skeletal muscle.

Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3h post-exercise in hypoxia but not control. PGC1A mRNA increased 3h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.

A Sports Nutrition Perspective on the Impacts of Hypoxic High-Intensity Interval Training (HIIT) on Appetite Regulatory Mechanisms: A Narrative Review of the Current Evidence.

High-intensity interval training (HIIT) and low-oxygen exposure may inhibit the secretion of appetite-stimulating hormones, suppress appetite, and inhibit dietary intake. Physiological changes affecting appetite are frequent and include appetite hormone (ghrelin, leptin, PYY, and GLP-1) effects and the subjective loss of appetite, resulting in nutritional deficiencies. This paper is a narrative review of the literature to verify the HIIT effect on appetite regulation mechanisms and discusses the possible relationship between appetite effects and the need for high-intensity exercise training in a hypoxic environment. We searched MEDLINE/PubMed and the Web of Science databases, as well as English articles (gray literature by Google Scholar for English articles) through Google Scholar, and the searched studies primarily focused on the acute effects of exercise and hypoxic environmental factors on appetite, related hormones, and energy intake. In a general normoxic environment, regular exercise habits may have accustomed the athlete to intense training and, therefore, no changes occurred in their subjective appetite, but there is a significant effect on the appetite hormones. The higher the exercise intensity and the longer the duration, the more likely exercise is to cause exercise-induced appetite loss and changes in appetite hormones. It has not been clear whether performing HIIT in a hypoxic environment may interfere with the exerciser’s diet or the nutritional supplement intake as it suppresses appetite, which, in turn, affects and interferes with the recovery efficiency after exercise. Although appetite-regulatory hormones, the subjective appetite, and energy intake may be affected by exercise, such as hypoxia or hypoxic exercise, we believe that energy intake should be the main observable indicator in future studies on environmental and exercise interventions.

Role of the Wnt/β-Catenin Signaling Pathway in Reducing Lipogenesis of Obese Rats Under Hypoxic Exercise

Hypoxic exercise exerts a significant effect on body weight loss and body fat reduction. Methods: In the present study, we constructed an obese rat model and divided rats into the following groups: Normoxic quiet (C), Hypoxic quiet (H), Normoxic Exercise (CE), and Hypoxic Exercise (HE). We employed isobaric tags for relative and absolute quantification (iTRAQ) using proteomic technology to screen the differentially expressed proteins in the four groups. Additionally, we used Reduced-Representation Bisulfite Sequencing (RRBS) to analyze high-throughput DNA methylation profiles in both HE and CE groups. Finally, we screened and analyzed the CpG islands and Differentially Methylated Regions (DMRs) of genes related to the Wnt/β-catenin-signaling pathway. Results: The mRNA levels of gene products related to the Wnt/β-catenin-signaling pathway (i.e., c-myc and β-catenin) were significantly augmented (P<0.05) in the HE group compared to the CE group; the levels of APC and GSK3β were significantly diminished (P<0.05). The expression levels of the Wnt/β-catenin-signaling pathway proteins c-myc and β-catenin were also significantly increased in the HE group relative to the CE group (P<0.05). Among genes related to the Wnt-signaling pathway, the CpG-promoter methylation sites included Fzd2, Fzd9, Wnt16, Wnt2b, Sfrp2, Sfrp1, Sox2, and Sox1; the DMRs included CDC, Fzd10, Gsk-3β, PI3k, Wnt16 and Wnt6. Conclusions: Our present findings provide evidence that hypoxic exercise may inhibit adipogenesis and adipogenesis through canonical Wnt signaling.

Hypoxia and Hypoxic Exercise Induced Systemic Ros Disrupts the Redox Homeostasis in the Brain

Aim: We aimed to investigate the overall effects of hypoxic/normoxic exercise and hypoxia on redox status in both systemic circulation and brain, and to prove whether the variations in plasma redox status could affect the brain’s own redox homeostasis, vice versa. Methods: We designed hypoxic, normoxic exercise groups with their respective controls. We studied on redox status biomarkers i.e., hydroperoxide, low molecular weight thiols, protein thiols, total thiols, and advanced oxidation protein products in frontal cortex; total antioxidant and total oxidant status in the plasma. Results: There is no statistically significant difference observed in redox homeostasis of the brain after hypoxic and/or normoxic exercise or hypoxia itself with an increased systemic oxidant status. Conclusions: Live in hypoxia and exercise at normoxia might diminish the hazardous effect of ROS on the brain at hypoxia. From our findings, thiols, which are the indicators of the antioxidant power of the brain, are found to be protected in groups that are exposed to long-term hypoxia and exercise at normoxia. It might be possible that people who are exposed to hypoxia will be least affected by this damage with normoxic exercise, or even will not be affected at all. Keywords: Hypoxic exercise, Redox homeostasis, Brain, Plasma

Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.

AimHypoxia has been shown to reduce resistance exercise‐induced stimulation of protein synthesis and long‐term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here, we examine the effect of acute hypoxia on the activity of several signalling pathways involved in the regulation of muscle growth following a bout of resistance exercise.MethodsEight men performed two sessions of leg resistance exercise in normoxia or hypoxia (12% O2) in a randomized crossover fashion. Muscle biopsies were obtained at rest and 0, 90,180 minutes after exercise. Muscle analyses included levels of signalling proteins and metabolites associated with energy turnover.ResultsExercise during normoxia induced a 5‐10‐fold increase of S6K1Thr389 phosphorylation throughout the recovery period, but hypoxia blunted the increases by ~50%. Phosphorylation of JNKThr183/Tyr185 and the JNK target SMAD2Ser245/250/255 was increased by 30‐ to 40‐fold immediately after the exercise in normoxia, but hypoxia blocked almost 70% of the activation. Throughout recovery, phosphorylation of JNK and SMAD2 remained elevated following the exercise in normoxia, but the effect of hypoxia was lost at 90‐180 minutes post‐exercise. Hypoxia had no effect on exercise‐induced Hippo or autophagy signalling and ubiquitin‐proteasome related protein levels. Nor did hypoxia alter the changes induced by exercise in high‐energy phosphates, glucose 6‐P, lactate or phosphorylation of AMPK or ACC.ConclusionWe conclude that acute severe hypoxia inhibits resistance exercise‐induced mTORC1‐ and JNK signalling in human skeletal muscle, effects that do not appear to be mediated by changes in the degree of metabolic stress in the muscle.

Effect of a speed ascent to the top of Europe on cognitive function in elite climbers.

The combined effects of acute hypoxia and exercise on cognition remain to be clarified. We investigated the effect of speed climbing to high altitude on reactivity and inhibitory control in elite climbers. Eleven elite climbers performed a speed ascent of the Mont-Blanc (4810m) and were evaluated pre- (at 1000m) and immediately post-ascent (at 3835m). In both conditions, a Simon task was done at rest (single-task session, ST) and during a low-intensity exercise (dual-task session, DT). Prefrontal cortex (PFC) oxygenation and middle cerebral artery velocity (MCAv) were monitored using near-infrared spectroscopy and transcranial Doppler, respectively, during the cognitive task. Self-perceived mental fatigue and difficulty to perform the cognitive tests were estimated using a visual analog scale. Heart rate and pulse oxygenation (SpO2) were monitored during the speed ascent. Elite climbers performed an intense (~ 50% of the time ≥ 80% of maximal heart rate) and prolonged (8h58 ± 6min) exercise in hypoxia (minimal SpO2 at 4810m: 78 ± 4%). Reaction time and accuracy during the Simon task were similar pre- and post-ascent (374 ± 28ms vs. 385 ± 39ms and 6 ± 4% vs. 5 ± 4%, respectively; p > 0.05), despite a reported higher mental fatigue and difficulty to perform the Simon task post-ascent (all p < 0.05). The magnitude of the Simon effect was unaltered (p > 0.05), suggesting a preserved cognitive control post-ascent. Pattern of PFC oxygenation and MCAv differed between pre- and post-ascent as well as between ST and DT conditions. Cognitive control is not altered in elite climbers after a speed ascent to high-altitude despite substantial cerebral deoxygenation and fatigue perception.

Effects of Pre-Term Birth on the Cardio-Respiratory Responses to Hypoxic Exercise in Children.

Pre-term birth is associated with numerous cardio-respiratory sequelae in children. Whether these impairments impact the responses to exercise in normoxia or hypoxia remains to be established. Fourteen prematurely-born (PREM) (Mean ± SD; gestational age 29 ± 2 weeks; age 9.5 ± 0.3 years), and 15 full-term children (CONT) (gestational age 39 ± 1 weeks; age 9.7 ± 0.9 years), underwent incremental exercise tests to exhaustion in normoxia (FiO2 = 20.9%) and normobaric hypoxia (FiO2 = 13.2%) on a cycle ergometer. Cardio-respiratory variables were measured throughout. Peak power output was higher in normoxia than hypoxia (103 ± 17 vs. 77 ± 18 W; p < 0.001), with no difference between CONT and PREM (94 ± 23 vs. 86 ± 19 W; p = 0.154). VO2peak was higher in normoxia than hypoxia in CONT (50.8 ± 7.2 vs. 43.8 ± 9.9 mL·kg−1·min−1; p < 0.001) but not in PREM (48.1 ± 7.5 vs. 45.0 ± 6.8 mL·kg−1·min−1; p = 0.137; interaction p = 0.044). Higher peak heart rate (187 ± 11 vs. 180 ± 10 bpm; p = 0.005) and lower stroke volume (72 ± 13 vs. 77 ± 14 mL; p = 0.004) were observed in normoxia versus hypoxia in CONT, with no such differences in PREM (p = 0.218 and >0.999, respectively). In conclusion, premature birth does not appear to exacerbate the negative effect of hypoxia on exercise capacity in children. Further research is warranted to identify whether prematurity elicits a protective effect, and to clarify the potential underlying mechanisms.

Repeated Ischemic Preconditioning Effects on Physiological Responses to Hypoxic Exercise.

INTRODUCTION: Repeated ischemic preconditioning (IPC) can improve muscle and pulmonary oxygen on-kinetics, blood flow, and exercise efficiency, but these effects have not been investigated in severe hypoxia. The aim of the current study was to evaluate the effects of 7 d of IPC on resting and exercising muscle and cardio-pulmonary responses to severe hypoxia.METHODS: A total of 14 subjects received either: 1) 7 d of repeated lower-limb occlusion (4 × 5 min, 217 ± 30 mmHg) at limb occlusive pressure (IPC) or SHAM (4 × 5 min, 20 mmHg). Subjects were tested for resting limb blood flow, relative microvascular deoxyhemoglobin concentration ([HHB]), and pulmonary oxygen (Vo2p) responses to steady state and incremental exercise to exhaustion in hypoxia (fractional inspired O₂ = 0.103), which was followed by 7 d of IPC or SHAM and retesting 72 h post-intervention.RESULTS: There were no effects of IPC on maximal oxygen consumption, time to exhaustion during the incremental test, or minute ventilation and arterial oxygen saturation. However, the IPC group had higher delta efficiency based on pooled results and lower steady state Δ[HHB] (IPC ∼24% vs. SHAM ∼6% pre to post), as well as slowing the [HHB] time constant (IPC ∼26% vs. SHAM ∼3% pre to post) and reducing the overshoot in [HHB]: Vo₂ ratio during exercise onset.CONCLUSIONS: Collectively, these results demonstrate that muscle O₂ efficiency and microvascular O₂ distribution can be improved by repeated IPC, but there are no effects on maximal exercise capacity in severe hypoxia.Chopra K, Jeffries O, Tallent J, Heffernan S, Kilduff L, Gray A, Waldron M. Repeated ischemic preconditioning effects on physiological responses to hypoxic exercise. Aerosp Med Hum Perform. 2022; 93(1):13-21.

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia.

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1) 75 g of ketone ester (KE), 2) 300 mg/kg body mass bicarbonate (BIC), 3) KE+BIC, or 4) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

The Effects of Sodium Phosphate Supplementation on the Cardiorespiratory System and Gross Efficiency during Exercise under Hypoxia in Male Cyclists: A Randomized, Placebo-Controlled, Cross-Over Study.

The main aim of this study was to evaluate the effects of six days of tri-sodium phosphate (SP) supplementation on the cardiorespiratory system and gross efficiency (GE) during exercise under hypoxia in cyclists. Twenty trained male cyclists received SP (50 mg·kg−1 of fat-free mass/day) or placebo for six days in a randomized, cross-over study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion under normobaric hypoxia (FiO2 = 16%, ~2500 m). It was observed that short-term SP supplementation led to a decrease in heart rate, an increase in stroke volume, and an improvement in oxygen pulse (VO2/HR) during low and moderate-intensity exercise under hypoxia. These changes were accompanied by an increase in the serum inorganic phosphate level by 8.7% (p < 0.05). No significant changes were observed in serum calcium levels. GE at a given workload did not change significantly after SP supplementation. These results indicated that SP promotes improvements in the efficiency of the cardiorespiratory system during exercise in a hypoxic environment. Thus, SP supplementation may be beneficial for endurance exercise in hypoxia.

Evaluation of the Lake Louise Score for Acute Mountain Sickness and Its 2018 Version in a Cohort of 484 Trekkers at High Altitude.

Richalet, Jean-Paul, Chantal Julia, and François J. Lhuissier. Evaluation of the Lake Louise Score for acute mountain sickness and its 2018 version in a cohort of 484 trekkers at high altitude. High Alt Med Biol. 22:353-361, 2021. Background: The Lake Louise Score (LLS) is widely used in field studies and chamber studies for the diagnosis of Acute Mountain Sickness (AMS). This score aggregates symptoms that are nonspecific: headache, gastrointestinal symptoms, fatigue, dizziness and sleep disturbance can be due to a variety of causes unrelated to altitude hypoxia. The objectives of this study were to (1) reevaluate the need for a headache score >0 for the diagnosis of AMS, (2) evaluate the role of sleep disturbances, in relation with other symptoms, (3) evaluate the significance of dizziness. Materials and Methods: We analyzed LLS from 484 trekkers at high altitude. Among them, 212 suffered from moderate AMS (mAMS: 3 ≤ LLS < 6) and 115 from severe AMS (sAMS: LLS ≥ 6). Results: Cluster analysis of AMS revealed three main groups presenting the following symptoms: Group 1 includes 254 subjects who had less than 2 symptoms; Group 2 includes 137 subjects who had fatigue, sleep disturbance, and headache, corresponding to mAMS; Group 3 includes 93 subjects who had headache, fatigue, dizziness and sleep disturbance, corresponding to sAMS. A headache score of zero was found in 25% of mAMS and 5% of sAMS subjects. Only the absence of headache associated with the absence of fatigue was specific of absence of sAMS. In subjects with a dizziness score > 1, end-tidal partial pressure of carbon dioxide during a hypoxic exercise test was lower than that in subjects with a dizziness score < 2. Subjects with high ventilatory response to hypoxia may develop dizziness with high altitude exposure. Conclusion: (1) An isolated headache score > 0 should not be mandatory to define AMS, (2) sleep disruption contributes to the diagnosis of AMS, (3) gastrointestinal symptoms and dizziness are weaker contributors to the LLS, (4) dizziness might be linked to a hyperresponsiveness to hypoxia and not to AMS itself.

근 기능 개선 및 근 비대를 위한 저산소 환경에서의 저항성 트레이닝의 효용성 검증 - 문헌적 고찰

We are generally believed that optimal muscular function and hypertrophy gains are induced via moderate- or high-intensity resistance training, equivalent to at least 70% of an individual’s 1 repetition maximum. In recent years, systemic hypoxic stress has emerged as a stimulation condition that can induce more physiological and biochemical changes caused by resistance exercise. Hypoxic stress result in changes in neuromotor control, metabolic changes, hormonal changes, cellular swelling, and intracellular signaling pathways, similar to the effects of resistance exercise. The combination of hypoxic stress and resistance exercise is expected to have a greater effect on the improvement of muscular function and hypertrophy. Therefore, we examined the previous studies for understand the concept of intermittent hypoxic resistance training (IHRT) and its effectiveness, and to grasp the principle of IHRT to improve muscular function and hypertrophy. However, few investigations have examined the combination effects of hypoxic stress and resistance exercise, and as such it is difficult to make recommendations for implementing IHRT based on current understanding. It should also be acknowledged that a number of mechanisms proposed to facilitate the augmented response to IHRT remain poorly understood, particularly the systemic role of metabolic, hormonal, cellular swelling, and intracellular signaling pathways. Future research should examine the various physiological and biochemical mechanism and performance to resistance exercise in hypoxic condition and training in systemic hypoxic condition.

Normobaric Hypoxia Exposure During Treadmill Aerobic Exercise After Stroke: A Safety and Feasibility Study.

ObjectiveTo evaluate the safety and feasibility of performing treadmill aerobic exercise in moderate normobaric hypoxia among chronic hemiparetic stroke survivors.DesignObservational study using convenience sampling.SettingResearch laboratory in a tertiary rehabilitation hospital.ParticipantsChronic hemiparetic stroke survivors who could walk at least 10-m with or without assistance and had no absolute contraindications to exercise testing.InterventionParticipants (three male and four female) were asked to complete three normobaric hypoxia exposure protocols within a single session. First, they were passively exposed to normobaric hypoxia through gradual reductions in the fraction of inspired oxygen (FIO2 = 20.9, 17.0, and 15.0%) while seated (5-min at each level of FIO2). Participants were then exposed to the same reductions in FIO2 during constant-load exercise performed on a treadmill at 40% of heart rate reserve. Finally, participants completed 20-min of exercise while intermittently exposed to moderate normobaric hypoxia (5 × 2-min at FIO2 = 15.0%) interspaced with 2-min normoxia intervals (FIO2 = 20.9%).Outcome MeasuresThe primary outcome was occurrence of adverse events, which included standardized criteria for terminating exercise testing, blood oxygen saturation (SpO2) <80%, or acute mountain sickness score >2. The increased cardiovascular strain imposed by normobaric hypoxia exposure at rest and during exercise was evaluated by changes in SpO2, heart rate (HR), blood pressure, and rating of perceived exertion (RPE).ResultsOne participant reported mild symptoms of nausea during exercise in normobaric hypoxia and discontinued participation. No other adverse events were recorded. Intermittent normobaric hypoxia exposure was associated with reduced SpO2 (MD = −7.4%, CI: −9.8 to −5.0) and increased HR (MD = 8.2, CI: 4.6 to 11.7) compared to intervals while breathing typical room air throughout the 20-min constant-load exercise period. The increase in HR was associated with a 10% increase in relative effort. However, reducing FIO2 had little effect on blood pressure and RPE measurements.ConclusionModerate normobaric hypoxia appeared to be a safe and feasible method to increase the cardiovascular strain of submaximal exercise in chronic hemiparetic stroke survivors. Future studies evaluating the effects of pairing normobaric hypoxia exposure with existing therapies on secondary prevention and functional recovery are warranted.

Sex-Specific Effects of Respiratory Muscle Endurance Training on Cycling Time Trial Performance in Normoxia and Hypoxia.

Objectives: We tested the hypotheses that respiratory muscle endurance training (RMET) improves endurance cycling performance differently in women and men and more so in hypoxia than in normoxia.Design: A prospective pre–post cross-over study with two testing conditions.Methods: Healthy and active women (seven, 24 ± 4 years, mean ± standard deviation [SD]) and men (seven, 27 ± 5 years) performed incremental cycling to determine maximum oxygen consumption (VO2peak) and power output (Wpeak) and on different days two 10-km cycling time trials (TTs) in normoxia and normobaric hypoxia (FiO2, 0.135, ~3,500 m equivalent), in a balanced randomized order. Next they performed supervised RMET in normoxia (4 weeks, 5 days/week, 30 min/day eucapnic hyperpnea at ~60% predicted maximum voluntary ventilation) followed by identical post-tests. During TTs, heart rate, ear oximetry reading, and Wpeak were recorded.Results: The VO2peak and Wpeak values were unchanged after RMET. The TT was improved by 7 ± 6% (p < 0.001) in normoxia and 16 ± 6% (p < 0.001) in hypoxia. The difference between normoxic and hypoxic TT was smaller after RMET as compared with that before RMET (14% vs. 21%, respectively, p < 0.001). All effects were greater in women (p < 0.001). The RMET did not change the heart rate or ear oximetry reading during TTs.Conclusion: We found a greater effect of RMET on cycling TT performance in women than in men, an effect more pronounced in hypoxia. These findings are congruent with the contention of a more pronounced performance-limiting role of the respiratory system during endurance exercise in hypoxia compared with normoxia and more so in women whose respiratory system is undersized compared with that of men.

Select DNA Replication And Repair Genes Are Transcriptionally Modified By Acute Exercise In Hypoxia

DNA replication and repair in eukaryote cells are critical processes that ensures the correct transfer of DNA material through mitosis. Errors in the replication and repair of DNA during and following cell division may lead to genome instability. PURPOSE: To investigate the regulation of select gene transcripts aligned to DNA replication and repair following exercise in hypoxia. METHODS: Twenty-four (n = 24) apparently healthy male participants were recruited (age 28 ± 5 years; mass 74 ± 8 kg; stature 177 ± 6 cm; VO2max hypoxia 45 ± 2 ml·kg-1·min-1: normoxia 60 ± 9 ml·kg-1·min-1), and completed 1 hr of exercise at a workload corresponding to 75% of pre-determined VO2max in hypoxia (Fio2 = 0.16%), and repeated in normoxia (Fio2 = 0.21%). RNA was extracted from whole blood. Two-colour oligonucleotide microarrays [for DNA primase subunit 1 - PRIM1; Chromatin assembly factor 1 subunit B - CHAF1B; and Werner syndrome RecQ like helicase - WRN] were processed on an Agilent DNA microarray scanner, while mRNA analysis was conducted using GeneSpring software incorporating checks for data normalisation, quality control, filtering grouping (by experimental condition) and statistical analysis (paired t-test with Benjamini & Hochberg False Discovery Rate corrections for multiple comparisons). RESULTS: Exercise performed in hypoxia per se downregulated PRIM1 and CHAF1B (p = 0.03 and p = 0.01 respectively vs. pre-exercise), with no change observed in normoxia (p > 0.05). Compared with normoxia, CHAF1B and WRN were differentially downregulated following exercise in hypoxia (p = 0.05 and p = 0.05 respectively vs. pre-exercise). CONCLUSION: Acute exercise in moderate hypoxia interferes with gene transcription aligned to blood cell DNA replication and repair. Further work is necessary to ascertain the consequence of these select modifications on genome stability.