Intermittent Hypoxic Exposure Research Articles

The Potential Interplay Between HIF-1α, Angiogenic, and Autophagic Signaling During Intermittent Hypoxic Exposure and Exercise.

Berkemeier QN, Deyhle MR, McCormick JJ, Escobar KA, Mermier CM. The Potential Interplay between HIF-1α, Angiogenic, and Autophagic Signaling during Intermittent Hypoxic Exposure and Exercise High Alt Med Biol. 00:000-000, 2024.-Berkemeier QN, Deyhle MR, McCormick JJ, Escobar KA, Mermier CM. The Potential Interplay between HIF-1α, Angiogenic, and Autophagic Signaling During Intermittent Hypoxic Exposure and Exercise High Alt Med Biol. 00:000-000, 2024.-Environmental hypoxia as a result of decreased barometric pressure upon ascent to high altitudes (>2,500 m) presents increased physiological demands compared with low altitudes, or normoxic environments. Competitive athletes, mountaineers, wildland firefighters, military personnel, miners, and outdoor enthusiasts commonly participate in, or are exposed to, forms of exercise or physical labor at moderate to high altitudes. However, the majority of research on intermittent hypoxic exposure is centered around hematological markers, and the skeletal muscle cellular responses to exercise in hypoxic environments remain largely unknown. Two processes that may be integral for the maintenance of cellular health in skeletal muscle include angiogenesis, or the formation of new blood vessels from preexisting vasculature and autophagy, a process that removes and recycles damaged and dysfunctional cellular material in the lysosome. The purpose of this review is to is to examine the current body of literature and highlight the potential interplay between low-oxygen-sensing pathways, angiogenesis, and autophagy during acute and prolonged intermittent hypoxic exposure in conjunction with exercise.The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army, DOD, DOE, ORAU/ORISE or U.S. Government.

Ethanol pre-exposure attenuates the hypoxic ventilatory response and may attenuate expression of long term facilitation following intermittent hypoxia treatment in adult rats

Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in which airway collapse or obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures during sleep can induce intermittent hypoxemia, sympathetic activation, and sleep fragmentation which can lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia, which consists of alternating exposure to hypoxia and normal oxygen levels (normoxia), can induce a long-lasting increase in breathing motor output called long term facilitation (LTF) and is currently being investigated as a therapeutic treatment. Interestingly, experts in the field of LTF have noted how IH models some key aspects of OSA. It has been well established through clinical studies that ethanol consumption prior to sleep exacerbates existing OSA, increasing the apnea/hypopnea index and worsening arterial blood oxygen desaturations during the night. However, it is unknown whether ethanol affects expression of LTF following IH treatment. If LTF might serve as a means of increasing ventilatory output to compensate for periods of apnea and hypopnea during OSA, ethanol might not only worsen the severity of OSA, but impede individuals’ compensatory response. Thus, for this study we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the hypoxic ventilatory response during IH treatment. Using adult female Sprague-Dawley rats, we administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol through intraperitoneal injection to model a 2-drink nightcap or binge drinking-type ethanol exposure, respectively. Immediately afterwards, we measured subjects’ ventilatory output during baseline, then during a 5 by 3-minute moderate IH protocol, and for one hour following the end of IH using whole-body plethysmography. Finally, we took venous blood samples to assay serum ethanol concentration at the end of the approximately 2.5 hour plethysmography measurement. Results from the high-dose ethanol group indicate that ethanol pre-exposure might attenuate respiratory rate and minute volume LTF in comparison to saline-treated control. Furthermore, high-dose ethanol attenuated the hypoxic ventilatory response with respect to respiratory rate and minute volume. Low dosage of ethanol attenuated subjects’ HVR of respiratory rate and minute volume, but conflictingly trends towards increasing LTF of tidal volume while diminishing LTF of respiratory rate when compared to saline control. Overall, our findings indicate that high levels of ethanol exposure dramatically diminish the acute ventilatory response to hypoxic exposure and may impede long-term increases in ventilatory output following IH treatment. On the other hand, lower doses of ethanol have a subtler effect on the ventilatory response to hypoxia. Future directions will include analysis of additional parameters of ventilatory function to gain a more detailed understanding of how ethanol effects respiratory plasticity in the context of intermittent hypoxic exposure. NIH 5T32 AA027488 to ALSUniversity of Kentucky Endowment to WJA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis.

This study aimed to separately compare and rank the effect of various living-low and training-high (LLTH) modes on aerobic and anaerobic performances in athletes, focusing on training intensity, modality, and volume, through network meta-analysis. We systematically searched PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023. Based on the hypoxic training modality and the intensity and duration of work intervals, LLTH was divided into intermittent hypoxic exposure, continuous hypoxic training, repeated sprint training in hypoxia (RSH; work interval: 5-10 s and rest interval: approximately 30 s), interval sprint training in hypoxia (ISH; work interval: 15-30 s), short-duration high-intensity interval training (s-IHT; short work interval: 1-2 min), long-duration high-intensity interval training (l-IHT; long work interval: > 5 min), and continuous and interval training under hypoxia. A meta-analysis was conducted to determine the standardized mean differences (SMDs) among the effects of various hypoxic interventions on aerobic and anaerobic performances. From 2,072 originally identified titles, 56 studies were included in the analysis. The pooled data from 53 studies showed that only l-IHT (SMDs: 0.78 [95% credible interval; CrI, 0.52-1.05]) and RSH (SMDs: 0.30 [95% CrI, 0.10-0.50]) compared with normoxic training effectively improved athletes' aerobic performance. Furthermore, the pooled data from 29 studies revealed that active intermittent hypoxic training compared with normoxic training can effectively improve anaerobic performance, with SMDs ranging from 0.97 (95% CrI, 0.12-1.81) for l-IHT to 0.32 (95% CrI, 0.05-0.59) for RSH. When adopting a program for LLTH, sufficient duration and work intensity intervals are key to achieving optimal improvements in athletes' overall performance, regardless of the potential improvement in aerobic or anaerobic performance. Nevertheless, it is essential to acknowledge that this study incorporated merely one study on the improvement of anaerobic performance by l-IHT, undermining the credibility of the results. Accordingly, more related studies are needed in the future to provide evidence-based support. It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.

Intermittent hypoxia exposure at sea level improves functional capacity (6MWT) at high altitude

Objectives: Our primary objective is to observe whether acclimatisation is elicited by the intermittent hypoxic exposure (IHE) protocol. For this, we have utilised performance in a 6-min walk test (6MWT) as a tool to assess physiological responses to high altitude (HA) both in control and IHE-exposed groups, respectively. Materials and Methods: The study was a prospective cohort study conducted on Indian army volunteers (n = 57) and they were divided into two groups, a control group (CG) and an experimental group (EG). At the sea level, a baseline study was carried out on barometric pressure. IHE was performed at sea level in the normobaric hypoxia chamber (low fraction of inspired oxygen [FiO2], at normal barometric pressure, 740 mmHg), in which the FiO2 of the chamber was artificially decreased using O2-filtering membranes. The oxygen percentage was constantly maintained at 12%-13%. After recording the baseline, the subjects were exposed to a normobaric hypoxia chamber at 12%-13% FiO2 (altitude – equivalent to 4350 m Approx). Heart rate and blood pressure (BP) were recorded with a battery-operated portable BP monitor (OMRON) at both locations. A finger pulse oximeter probe was set on the right index finger to measure the resting oxygen saturation (SpO2) level (Model MU 300). Incidence of acute mountain sickness (AMS) was scored with the help of the standard Lake Louise questionnaire (LLS). Total LLS scores more than >3 (range 0–15) were considered AMS. Results: EG individuals that went through IHE performed better at 6MWT at Stage I (P = 0.03). EG also had better SpO2, levels as compared to CG (P = 0.00) at Stage II (P = 0.03). Furthermore, there was a significant difference in the Borg’s Scale between CG and EG. The Delta SpO2 of EG was better as compared to CG in all stages, albeit not significant (P = 0.07). There was a significant difference between IHE and CG groups, and CG was at an increased risk for lower SpO2 (8.00 [1.21–52.60], P = 0.03). Conclusion: The findings elucidate the benefits of IHE in rapid acclimatisation, and it contributed to better distance covered as shown by 6MWT as well and reduces hypoxic incidents in HA.

Optimal type and dose of hypoxic training for improving maximal aerobic capacity in athletes: a systematic review and Bayesian model-based network meta-analysis.

Objective: This study aimed to compare and rank the effect of hypoxic practices on maximum oxygen consumption (VO2max) in athletes and determine the hypoxic dose-response correlation using network meta-analysis. Methods: The Web of Science, PubMed, EMBASE, and EBSCO databases were systematically search for randomized controlled trials on the effect of hypoxc interventions on the VO2max of athletes published from inception until 21 February 2023. Studies that used live-high train-high (LHTH), live-high train-low (LHTL), live-high, train-high/low (HHL), intermittent hypoxic training (IHT), and intermittent hypoxic exposure (IHE) interventions were primarily included. LHTL was further defined according to the type of hypoxic environment (natural and simulated) and the altitude of the training site (low altitude and sea level). A meta-analysis was conducted to determine the standardized mean difference between the effects of various hypoxic interventions on VO2max and dose-response correlation. Furthermore, the hypoxic dosage of the different interventions were coordinated using the "kilometer hour" model. Results: From 2,072 originally identified titles, 59 studies were finally included in this study. After data pooling, LHTL, LHTH, and IHT outperformed normoxic training in improving the VO2max of athletes. According to the P-scores, LHTL combined with low altitude training was the most effective intervention for improving VO2max (natural: 0.92 and simulated: 0.86) and was better than LHTL combined with sea level training (0.56). A reasonable hypoxic dose range for LHTH (470-1,130kmh) and HL (500-1,415kmh) was reported with an inverted U-shaped curve relationship. Conclusion: Different types of hypoxic training compared with normoxic training serve as significant approaches for improving aerobic capacity in athletes. Regardless of the type of hypoxic training and the residential condition, LHTL with low altitude training was the most effective intervention. The characteristics of the dose-effect correlation of LHTH and LHTL may be associated with the negative effects of chronic hypoxia.

Intermittent Hypoxic Exposure And Training Have Potential To Maintain Elevated Hemoglobin Mass After Hypoxic Camps

Intermittent Hypoxic Exposure And Training Have Potential To Maintain Elevated Hemoglobin Mass After Hypoxic Camps

Intermittent hypoxic exposure and exercise training positively affect body composition and energy substrate utilization in high-fat diet-induced obese mice

Obesity is considered a major risk factor for increasing insulin resistance and inducing type 2 diabetes. Exercise is known to be the most effective treatment for improving obesity and insulin resistance through body fat loss. Furthermore, hypoxic exposure is known to increase carbohydrate oxidation and improve overall energy expenditure. Therefore, in this study, the effect of combined treatment of exercise and intermittent hypoxia on body composition and metabolic improvement was investigated after inducing obesity through a high-fat diet.The male 5-week-old ICR mice consumed high-fat diet for 7 weeks and were fed ad libitum. After 7 weeks, all groups were randomly divided into 4 groups: CN (sedentary; non-trained), HP (hypoxic exposure; non-trained), EX (trained), and HE (hypoxic exposure and trained). The HP and HE were only exposed hypoxia condition (12% oxygen concentration) for during light phase to coincide with the mouse inactive cycle. The EX and HE conducted treadmill training with 5 times a week for 4 weeks, and the exercise intensity was 70 % of VO2 max. After 4 weeks, the resting metabolic rate (RMR) was measured for all groups through respiratory gas. Then, all mice conducted dual energy X-ray absorptiometry to determine body composition.In body composition results, long-term exercise treatment showed a significantly decrease in fat mass and a significant increase in lean mass. In addition, in the HE, had significantly lower body fat mass and significantly higher lean mass than the EX. Furthermore, in the RMR results, it was investigated that overall energy expenditure increased through an increase in VO2 and VCO2 in the exercise group. However, in the HE, it was confirmed that carbohydrate oxidation at rest was significantly higher than that of the EX. In addition, it was confirmed that fasting blood glucose and HOMA-IR, an indicator of insulin resistance, were also significantly improved in the HE than in the EX.In summary, these results demonstrated that long-term exercise training decrease fat mass and increase in lean mass in high-fat diet-induced obese mice. In addition, it was confirmed that the HE, which intermittent hypoxic exposure combined treatment with exercise, significantly improved body composition compared to the EX, as well as improved carbohydrate oxidation at rest, fasting blood glucose, and HOMA-IR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exposure to Intermittent Environmental Hypoxia Promotes Vascular Remodeling through Angiogenesis in the Liver of Largemouth Bass (Micropterus salmoides).

In this study, we explored the effects of 4 weeks of intermittent hypoxic exposure (IHE) on liver angiogenesis and related regulatory mechanisms in largemouth bass (Micropterus salmoides). The results indicated that the O2 tension for loss of equilibrium (LOE) decreased from 1.17 to 0.66 mg/L after 4 weeks of IHE. Meanwhile, the red blood cell (RBC) and hemoglobin concentrations significantly increased during IHE. Our investigation also found that the observed increase in angiogenesis was correlated with a high expression of related regulators, such as Jagged, phosphoinositide-3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). After 4 weeks of IHE, the overexpression of factors related to angiogenesis processes mediated by HIF-independent pathways (such as nuclear factor kappa-B (NF-κB), NADPH oxidase 1 (NOX1), and interleukin 8 (IL8)) was correlated with the accumulation of lactic acid (LA) in the liver. The addition of cabozantinib, a specific inhibitor of VEGFR2, blocked the phosphorylation of VEGFR2 and downregulated the expression of downstream angiogenesis regulators in largemouth bass hepatocytes exposed to hypoxia for 4 h. These results suggested that IHE promoted liver vascular remodeling by the regulation of angiogenesis factors, presenting a potential mechanism for the improvement of hypoxia tolerance in largemouth bass.

Does intermittent hypoxic exposure enhance the cardioprotective effect of exercise in an inactive population?

The aim of this study was to determine whether exercise supplemented with passive intermittent hypoxic exposure (IHE) improved overall cardiovascular disease risk and individual risk factors. Participants were randomized to exercise-only (Ex, n = 18, 5 males, 13 females; age: 56.4 ± 6.5years; weight: 81.2 ± 15.9; height: 167.3 ± 8.42) or exercise + IHE (IHE + Ex, n = 16; 6 males, 10 females; age: 56.7 ± 6.4years; weight: 78.6 ± 12.4kg; height: 168.0 ± 8.8cm). Both groups received the same strength and aerobic exercise training (1h, 3days/wk, 10weeks). IHE + Ex also received IHE (5min hypoxia: 5min ambient air ×6) for 2-3days/wk. Measurements were collected before (Baseline), after (Post), and 4- and 8-week following the intervention. There were small, beneficial reductions in overall 5- year cardiovascular risk in both groups. At Post, for IHE + Ex compared to IHE there were unclear to likely improvements in high density lipoprotein (8.0% ± 8.0%), systolic blood pressure (-3.4% ± 3.4%) and VO2peak (3.1% ± 7.7%). These improvements persisted at 8-week. There was an unclear improvement in arterial wave reflection (augmentation index) at Post (-6.1% ± 18.4%, unclear), but became very likely harmful at 8-week (8-week: 24.8% ± 19.7%). The conflicting findings indicate that in inactive adults, the addition of IHE to exercise may be beneficial to systemic markers of cardiovascular health but may also increase myocardial load due to increased arterial wave reflection.

EFFECTS OF INTERMITTENT HYPOXIA EXPOSURE ON LEUKOCYTE COUNT AND ANXIETY IN EXERCISE-INDUCED HYPOHEMOGLOBIN RATS

BackgroundHypoxia training is an effective method and tool widely used in sports training. Altitude training (hypoxia training) has been widely used by athletes to improve their aerobic capacity. Hypoxia can induce gene expression regulated by hypoxia inducible factor (HIF), then stimulate the production of erythropoietin (EPO), and finally promote the synthesis of hemoglobin. In the process of hypoxic training, the body is under the dual stimulation of hypoxic environment and exercise, which has a significant impact on peripheral blood immune cells, while high-intensity incremental load exercise in hypoxic environment will greatly change the level of psychological stress. To study the effects of intermittent hypoxic stimulation on leukocytes and psychological stress in exercise-induced low hemoglobin rats, so as to provide reference for the selection of high-intensity hypoxic training mode.Participants and Methods60 6-week-old healthy male SD rats underwent 6-week incremental load running to establish exercise-induced low globulin model. Rats in each group were exposed to hypoxia for 1 hour, 2 hours and (1 + 1) hours at intervals of (1 + 1) hours and (1 + 1) hours in the atmospheric hypoxia chamber. In the artificial atmospheric anoxic environment, the anoxic concentration is controlled at about 14.5%. In addition to intermittent hypoxic exposure, rats were free to move in an additional compartment normoxia environment for 6 days per week for 3 weeks. After 3 weeks, the erythrocyte (RBC), hemoglobin (HB), erythrocyte pressure (HCT), total leukocyte (WBC), neutrophil (neut), lymphocyte (lymph), monocyte (mono), eosinophil (aacidphil) and basophil (basophil) counts of exercise-induced hemoglobin hypoglobulin rats were measured, and the stress state of rats was observed and compared with that of normoxia recovery group. At the same time, there is a very significant positive correlation between state anxiety and trait anxiety. The anxiety component of mouse characteristics plays an important role in the generation of foreign language learning anxiety. Studies have shown that rat anxiety and activity efficacy can be used as comprehensive variables to measure rat state.ResultsAfter 1 hour, 2 hours and (1 + 1) hours of hypoxia exposure, the levels of hemoglobin, erythrocyte and HCT in the recovery group were significantly higher than those in the normoxia recovery group (P < 0.05, P < 0.01), and the leukocyte count in the hemoglobin inhibition model group was significantly lower than that in the control group (P < 0.01). Comparing three different hypoxia exposure modes, the (1 + 1) hour hypoxia exposure recovery group was more effective in preventing exercise-induced hypohemoglobin. Among the three types of hypoxia exposure, the leukocyte count in the 2-hour hypoxia exposure recovery group was significantly lower than that in the normoxia recovery group (P < 0.05), and there was no significant difference among other groups (P > 0.05). Except that there was no significant difference between the pre-test (M = 3.139, SD = 0.858) and post test (M = 3.750, SD = 0.996) scores of the “self-efficacy dimension of feeling positive emotions”, the subjects in the experimental group were pre-test (M = 3.250, SD = 0.684) and post test (m = 4.333, SD = 1.172) and pre-test (M = 2.528, SD = 0.540) and post test (M = 3.278, SD = 1.099) of the “self-efficacy dimension of feeling positive emotions” There were significant differences in the pre-test (M = 2.778, SD = 0.770) and post-test (M = 3.278, SD = 1.099) and the total score of emotion regulation self-efficacy (M = 35.083, SD = 5.931) and post-test (M = 43.917, SD = 8.806), and the post-test score was significantly higher than the pre-test score. That is, through intervention training, the scores of subjects in these dimensions have been significantly improved.ConclusionHypoxia exposure can promote erythropoiesis and help to recover from exercise-induced hypoglycemia, while low-dose intermittent hypoxia exposure has little effect on immune function, and multiple low-dose hypoxia exposure has little effect on the level of psychological stress. The research results can be applied to the practice of sports training and improve the performance of sports training. Its mechanism needs to be further studied.AcknowledgementsSupported by the Science and Technology Fund of Guizhou Province (No. LKA 201807).

Intermittent Hypoxia Exposure Can Prevent Reductions in Hemoglobin Concentration After Intense Exercise Training in Rats.

Intense exercise training can induce low concentrations of hemoglobin, which may be followed by maladaptation. Therefore, it is important for athletes to prevent low concentrations of hemoglobin during intense exercise training. In this study, we explored whether different protocols of intermittent hypoxic exposure (IHE, normobaric hypoxia, 14.5% O2) could prevent the exercise training-induced reduction in hemoglobin concentration in rats. Six-week-old male Sprague-Dawley rats were subjected to progressive intense treadmill exercise training over three weeks followed by three weeks of training with IHE after exercise. IHE lasted either 1 h, 2 h, or 1 h + 1 h (separated by a 3-h interval) after the exercise sessions. Hematological parameters, including hemoglobin concentration [(Hb)], red blood cells (RBCs), and hematocrit (Hct), and both renal and serum erythropoietin (EPO) were examined. We found that intense exercise training significantly reduced [Hb], RBCs, Hct, food intake and body weight (P < 0.01). Analysis of reticulocyte hemoglobin content (CHr) and reticulocyte counts in the serum of the rats suggested that this reduction was not due to iron deficiency or other cofounding factors. The addition of IHE after the intense exercise training sessions significantly alleviated the reduction in [Hb], RBCs, and Hct (P < 0.05) without an obvious impact on either food intake or body weight (P > 0.05). Increase in reticulocyte count in the rats from the IHE groups (P < 0.05 or P < 0.01) suggests that IHE promotes erythropoiesis to increase the hemoglobin concentration. Furthermore, the addition of IHE after the intense exercise training sessions also significantly increased the concentration of renal EPO (P < 0.05), although the increase of the serum EPO level was statistically insignificant (P > 0.05). The different IHE protocols were similarly effective at increasing renal EPO and preventing the training-induced decreases in [Hb], RBCs, and Hct. Collectively, this study suggests that IHE may be used as a new strategy to prevent intense exercise training-induced reductions in [Hb], and deserves future exploration in athletes.

Hypoxia, energy balance, and obesity: An update.

Because of the enduring rise in the prevalence of obesity worldwide, there is continued interest in hypoxia as a mechanism underlying the pathophysiology of obesity and its comorbidities and as a potential therapeutic adjunct for the management of the disease. Lifelong exposure to altitude is accompanied by a lower risk for obesity, whereas altitude sojourns are generally associated with a loss of body mass. A negative energy balance upon exposure to hypoxia can be due to a combination of changes in determinants of energy expenditure (resting metabolic rate and physical activity energy expenditure) and energy intake (appetite). Over the past 15 years, the potential therapeutic interest of hypobaric or normobaric hypoxic exposure in individuals with obesity-to lower body mass and improve health status-has become an active field of research. Various protocols have been implemented, using actual altitude sojourns or intermittent normobaric hypoxic exposures, at rest or in association with physical activity. Although several studies suggest benefits on body mass and cardiovascular and metabolic variables, further investigations are required before recommending hypoxic exposure in obesity management programs. Future studies should also better clarify the effects of hypoxia on appetite, the intestinal microbiota, and finally on overall energy balance.

Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review

ObjectiveSeveral working groups (eg, miners, flight crews and soldiers) are subjected to chronic intermittent hypoxic exposure. The cardiovascular implications have been studied but not systematically reviewed with focus on possible...

Intermittent Hypoxic Exposure with High Dose of Arginine Impact on Circulating Mediators of Tissue Regeneration.

Intermittent exposure to hypoxia (IHE) increases production of reactive oxygen and nitrogen species which, as signalling molecules, participate in tissue injury–repair–regeneration cascade. The process is also stimulated by arginine whose bioavailability is a limiting factor for NO synthesis. The effects of IHE in combination with arginine (Arg) intake on myogenesis and angiogenesis mediators were examined in a randomized and placebo-controlled trial. Blood samples were collected from 38 elite athletes on the 1st, 7th and 14th days during the training camp. The oral doses of arginine (2 × 6 g/day) and/or IHE using hypoxicator GO2Altitude (IHE and Arg/IHE) were applied. Serum NO and H2O2 concentrations increased significantly and were related to muscle damage (CK activity >900 IU/mL) in IHE and Arg/IHE compared to placebo. The changes in NO and H2O2 elevated the levels of circulating growth factors such as HGF, IHG-1, PDGFBB, BDNF, VEGF and EPO. Modification of the lipid profile, especially reduced non-HDL, was an additional beneficial effect of hypoxic exposure with arginine intake. Intermittent hypoxic exposure combined with high-dose arginine intake was demonstrated to affect circulating mediators of injury–repair–regeneration. Therefore, a combination of IHE and arginine seems to be a potential therapeutic and non-pharmacological method to modulate the myogenesis and angiogenesis in elite athletes.

The effect of intermittent hypoxic exposure on erythropoietic response and hematological variables in elite athletes.

This study aimed to evaluate the changes in the erythropoietin level and hematological variables in wrestlers after intermittent hypoxic exposure (IHE). Twelve wrestlers were assigned into two groups: hypoxia (sports training combined with IHE, n=6) and control (sports training, n=6). An IHE was performed for 10 days, with one day off after 6 days, once a day for about an hour. The concentrations of hydrogen peroxide ( H(2)O(2) ), nitric oxide (NO), vascular endothelial growth factor (VEGF) and erythropoietin (EPO), as well as total creatine kinase activity (CK) were measured. Also, the hematological markers (Hb - hemoglobin, Ht - hematocrit, RBC - red blood cell, WBC - white blood cell, Ret - reticulocytes) were analyzed. The 6-day IHE caused an increase in the levels of H(2)O(2), NO and VEGF. Similarly, the EPO level and WBC count reached the highest value after 6 days of IHE. The total Ret number increase constantly during 10 days of IHE. The hypoxia group showed a higher CK activity compared to the control. In conclusion, 10-day IHE in combination with wrestling training elevates levels of H(2)O(2), NO and VEGF, and improves the oxygen transport capacity by the release of EPO and Ret in circulation.

The Effects of Apnea Training, Using Voluntary Breath Holds, on High Altitude Acclimation: Breathe-High Altitude Study.

Introduction: There is evidence that intermittent hypoxic exposure (IHE) may improve high altitude (HA) performance. In this study, the effects of short-term IHE through voluntary apnea training on HA-related symptoms, including acute mountain sickness (AMS), were examined for the first time. Methods: Forty healthy adults were randomized to a self-administered apnea training (n = 19) or control (n = 21 no apnea training) group before ascent to an altitude of 5100 m in the Himalayas over 14 days. The apnea training was conducted at sea level (SL) and consisted of five breath holds per day in week 1, seven in week 2, followed by 10 per day from weeks 3 to 6 and until HA exposure. Saturation of arterial oxygen (SpO2), heart rate, sleep quality (Insomnia Severity Index [ISI]), rating of perceived exertion (RPE), blood pressure, and Lake Louise scores were measured at SL (in the United Kingdom) and at HA at 1400, 2700, 3400-3700, 4050-4200, 4800, and 5100-5200 m. Anxiety (Generalized Anxiety Disorder-7 [GAD-7]) scores were examined at SL, 1400, and 5100-5200 m. Results: Apnea training led to a significant increase in the mean longest breath-hold times from baseline (80.42 ± 32.49 [median 87.00] seconds) to the end of week 6 (107.02 ± 43.65 [113.00] seconds), respectively (p = 0.009). There was no significant difference in the prevalence of AMS (8/19 = 42.1% vs. 11/21 = 52.4%; RR 0.80; 95% confidence interval 0.41-1.57: p = 0.80) or in GAD-7, ISI and RPE, SpO2, heart rate, or blood pressure among the apnea versus control groups, respectively, at HA. Conclusions: Apnea training does not lessen HA-related symptoms in healthy adults traveling up to 5200 m. Larger studies using more challenging apnea protocols and at higher altitudes should be considered.

An Updated Panorama of "Living Low-Training High" Altitude/Hypoxic Methods.

With minimal costs and travel constraints for athletes, the “living low-training high” (LLTH) approach is becoming an important intervention for modern sport. The popularity of the LLTH model of altitude training is also associated with the fact that it only causes a slight disturbance to athletes' usual daily routine, allowing them to maintain their regular lifestyle in their home environment. In this perspective article, we discuss the evolving boundaries of the LLTH paradigm and its practical applications for athletes. Passive modalities include intermittent hypoxic exposure at rest (IHE) and Ischemic preconditioning (IPC). Active modalities use either local [blood flow restricted (BFR) exercise] and/or systemic hypoxia [continuous low-intensity training in hypoxia (CHT), interval hypoxic training (IHT), repeated-sprint training in hypoxia (RSH), sprint interval training in hypoxia (SIH) and resistance training in hypoxia (RTH)]. A combination of hypoxic methods targeting different attributes also represents an attractive solution. In conclusion, a growing number of LLTH altitude training methods exists that include the application of systemic and local hypoxia stimuli, or a combination of both, for performance enhancement in many disciplines.

Impact of intermittent hypoxic exposure on estrous cycle in female rats

Impact of intermittent hypoxic exposure on estrous cycle in female rats

Effects of exercise training with short-duration intermittent hypoxia on endurance performance and muscle metabolism in well-trained mice.

The author previously reported that short‐duration intermittent hypoxia had additive effects on improvements in endurance capacity by enhancing fatty acid metabolism. The present study was designed to investigate the effects of short‐duration intermittent hypoxia on endurance capacity, metabolic enzyme activity, and protein levels associated with mitochondrial biogenesis in well‐trained mice. Mice in the training group were housed in a cage with a running wheel for 7 weeks from 5 weeks old. Voluntary running markedly increased maximal work values by 5.0‐fold. Trained mice were then subjected to either endurance treadmill training (ET) for 60 min or hybrid training (HT, ET for 30 min followed by sprint interval exercise (5‐sec run‐10‐sec rest) for 30 min) with (H‐ET or H‐HT) or without (ET or HT) short‐duration intermittent hypoxia (4 cycles of 12–13% O2 for 15 min and 20.9% O2 for 10 min) for 4 weeks. Maximal endurance capacity was markedly greater in the H‐ET and H‐HT than ET and HT groups, respectively. H‐ET and H‐HT increased activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase in oxidative muscle portion and pyruvate dehydrogenase complex in glycolytic muscle portion. These activity levels were significantly correlated with maximal endurance capacity. Protein levels of dynamin‐related protein‐1 were increased more by H‐ET and H‐HT than by ET and HT, but were not significantly correlated with maximal work. These results suggest that intermittent hypoxic exposure has beneficial effects on endurance and hybrid training to improve the endurance capacity via improving fatty acid and pyruvate oxidation in highly trained mice.

Acute Psychophysiological Responses to Cyclic Variation of Intermittent Hypoxic Exposure in Adults with Obesity.

Background: We compared acute psychophysiological responses with a single intermittent hypoxic exposure (IHE)/normoxic exposure trial with varying cycle lengths in adults with obesity. Materials and Methods: Eight obese adults (body mass index = 33.0 ± 2.2 kg/m2) completed three 60-minute IHE trials (passive seating), separated by 7 days. Trials comprised 30-minute hypoxia/30-minute normoxia (inspired oxygen fraction = 12.0%/20.9%) over Short (15 × 2/2 minutes), Medium (10 × 3/3 minutes), and Long (5 × 6/6 minutes) hypoxic/normoxic cycles and a control trial (60-minute normoxia). Results: Arterial oxygen saturation was lower during hypoxic periods of Long versus Medium and Short trials (90.1% vs. 93.0% and 94.2%; p = 0.02 and p = 0.05), with no differences between Short and Medium. Prefrontal cortex oxygenation was lower (-5.1%) during all IHE interventions versus control (p < 0.02), independent of cycle length. Perceived breathlessness was unaffected during IHE but increased 15 minutes after exposure versus baseline (+34%; p = 0.04). Breathlessness was lowest after Short versus control from 15 to 60 minutes (-7%; p = 0.01). Conclusions: When implementing IHE, greater desaturation is observed during longer compared with shorter hypoxic/normoxic cycles in adults with obesity. However, IHE tends to be better tolerated perceptually with shorter rather than longer cycles.