Altitude Exposure Research Articles

Gypenosides (GPs) alleviates hypoxia-induced injury in PC12 cells and enhances tolerance to anoxia in C57BL/6 mice.

Oxygen is a necessary substance for life activities, but reduced oxygen utilization due to high altitude exposure and respiratory dysfunction diseases could lead to pathological changes in the organisms. Herein gypenosides, the active ingredients in the food and medicine resource plant Gynostemma pentaphyllum (Thunb.) Makino were found to alleviate hypoxia-induced injury in PC12 cells. Moreover, hypoxia induced an increase in Ca2+ and reactive oxygen species content, and such patterns were both significantly reduced by gypenosides treatment. At the same time, gypenosides significantly blocked the decrease of both NO content and mitochondrial membrane potential caused by hypoxia. Furthermore, gypenosides gavage treatment significantly prolonged the survival time of C57BL/6 mice in confinement up to 24.3% and enhanced the locomotor ability of mice. Therefore, gypenosides have good neuroprotective effects and hypoxia tolerance activity and have the prospect of being developed as a preventive and therapeutic drug for hypoxia-related diseases. PRACTICAL APPLICATIONS: Gypenosides can enhance tolerance of cells and mice to hypoxia and have the potential to be developed into hypoxia-resistant health food and drugs.

Acute high altitude exposure, acclimatization and re-exposure on nocturnal breathing.

Background: Effects of prolonged and repeated high-altitude exposure on oxygenation and control of breathing remain uncertain. We hypothesized that prolonged and repeated high-altitude exposure will improve altitude-induced deoxygenation and breathing instability. Methods: 21 healthy lowlanders, aged 18-30y, underwent two 7-day sojourns at a high-altitude station in Chile (4–8 hrs/day at 5,050 m, nights at 2,900 m), separated by a 1-week recovery period at 520 m. Respiratory sleep studies recording mean nocturnal pulse oximetry (SpO2), oxygen desaturation index (ODI, >3% dips in SpO2), breathing patterns and subjective sleep quality by visual analog scale (SQ-VAS, 0–100% with increasing quality), were evaluated at 520 m and during nights 1 and 6 at 2,900 m in the 1st and 2nd altitude sojourn. Results: At 520 m, mean ± SD nocturnal SpO2 was 94 ± 1%, ODI 2.2 ± 1.2/h, SQ-VAS 59 ± 20%. Corresponding values at 2,900 m, 1st sojourn, night 1 were: SpO2 86 ± 2%, ODI 23.4 ± 22.8/h, SQ-VAS 39 ± 23%; 1st sojourn, night 6: SpO2 90 ± 1%, ODI 7.3 ± 4.4/h, SQ-VAS 55 ± 20% (p < 0.05, all differences within corresponding variables). Mean differences (Δ, 95%CI) in acute effects (2,900 m, night 1, vs 520 m) between 2nd vs 1st altitude sojourn were: ΔSpO2 0% (-1 to 1), ΔODI -9.2/h (-18.0 to -0.5), ΔSQ-VAS 10% (-6 to 27); differences in acclimatization (changes night 6 vs 1), between 2nd vs 1st sojourn at 2,900 m were: ΔSpO2 -1% (-2 to 0), ΔODI 11.1/h (2.5 to 19.7), ΔSQ-VAS -15% (-31 to 1). Conclusion: Acute high-altitude exposure induced nocturnal hypoxemia, cyclic deoxygenations and impaired sleep quality. Acclimatization mitigated these effects. After recovery at 520 m, repeated exposure diminished high-altitude-induced deoxygenation and breathing instability, suggesting some retention of adaptation induced by the first altitude sojourn while subjective sleep quality remained similarly impaired.

Evidence For Sustained Physiological Adaptation From A Single Exercise Bout At Simulated Altitude

Intermittent exposures to normobaric or hypobaric hypoxia have been used to provide enhancements to oxygen delivery capabilities in athletes and in some patient populations as well as in the pre-acclimatization of individuals. The body is capable of very rapid adjustments to this type of environmental stress. However, it is somewhat unclear if an acute exposure to this type of environmental stress is enough to produce evidence of adaptations. PURPOSE: To examine evidence for physiological adaptation after a single bout of exercise at simulated altitude (Stratosphere Hypobaric Training Chamber) as determined from heart rate (HR), peripheral oxygen saturation (SpO2) and the ratio of hemoglobin O2 (oxygen) saturation in the circulating peripheral blood relative to HR (SpO2/HR) response. METHODS: 11 subjects (6 male, 5 female, age 36.5 ± 12.9 yrs, height 173.6 ± 9.2 cm, weight 75.7 ± 14.5 kg) completed 2 hypobaric chamber visits. During both visits, subjects performed a 30 min bout of exercise on a cycle ergometer at the same simulated altitude (2 km n = 1, 3 km n = 2, 4 km n = 8). Based on subjects previous VO2max test results, the exercise was divided into a light to moderate intensity for the first 15 min (target 50-60% WMax), immediately followed by a higher intensity (target 70-80% WMax) for the second 15 min. There was an average of 10 ± 6 days between each testing visit. Statistical analyses included paired samples t-test (p ≤ 0.05). RESULTS: There were no significant changes in workload (p = 0.28) or SpO2 (p = 0.67) between the two visits. However, there was a significant difference in HR (p < 0.001) and SpO2/HR (p < 0.001). There was an average decrease in HR of 19 bpm (12%) from visit 1 (155 ± 17 bpm) to visit 2 (136 ± 26 bpm), along with a 16% average increase in SpO2/HR from visit 1 (0.55 ± 0.06) to visit 2 (0.64 ± 0.13). The average workload across both intensity levels and altitudes were 97 ± 38 W for Visit 1 and 103 ± 39 W for Visit 2, with an average SpO2 of 84 ± 5% for both visits. CONCLUSION: These findings indicate an adaptive response to a short aerobic exercise bout during simulated altitude exposure that appears to be sustained greater than one week after the initial visit. Whether this is linked to oxygen sensing, neurally mediated or suggests early adjustments in oxygen delivery pathways is unclear, but appear unrelated to age, sex or fitness level.

Adequate exercise response at artificial altitude in Fontan patients

PurposeFor Fontan-palliated patients, altitude exposure is still a part of discussion since the extent of hypoxic pulmonary vasoconstriction potentially resulting in decreasing cardiac output (Qc), especially during physical exercise, is still unclear. We investigated the effects of normobaric hypoxia (15.2% O2) simulating 2,500 m above sea level on cardiopulmonary and metabolic parameters and the benefit of daily physical activity (PA) on hypoxic exercise capacity.MethodsA total of 21 Fontan patients (14–31 years) and 20 healthy controls performed cardiopulmonary exercise tests on a bicycle ergometer in normoxia and hypoxia until subjective exhaustion, measuring capillary lactate (cLa) every 2 min. In between, participants underwent an activity tracking over 5 days with a triaxial accelerometer.ResultsHypoxic exercise was well tolerated by Fontan patients, and no adverse clinical events were observed. Fontan patients showed reduced physical capacity under both conditions compared to controls (63% normoxia, 62% hypoxia), but the relative impairment due to hypoxia was similar for both (≈10%). Up to workloads of 2 W/kg oxygen uptake (O2) and heart rate (HR) developed similarly in patients and controls. cLa increased faster in relation to workload in Fontan patients, but remained significantly lower at peak workload (normoxia 3.88 ± 1.19 mmol/l vs. 7.05 ± 2.1 mmol/l; hypoxia 4.01 ± 1.12 mmol/l vs. 7.56 ± 1.82 mmol/l). Qc was diminished but could be increased similar to controls. Fontan patients with higher PA levels showed a higher O2peak in hypoxia.ConclusionExercise during short-time artificial altitude exposure seems to be safe for young Fontan patients. Further studies are needed to validate longer exposure under real conditions. O2, HR, and Qc might not be a limiting factor for exercise until workloads of 2 W/kg. Higher daily PA levels might improve physical capacity under altitude conditions.

Significance of Oxidative Stress Level Changing in Rat Cerebral Tissue following Hypobaric Hypoxia Exposure to Extreme/High Altitude and Different Exposure of Times

Aim: To elucidate brain damage under hypobaric hypoxia and changes in oxidative stress with ac. exposure to hypoxia in rats. Study Design: Experimental study. Place and duration of study: Department of Basic Medicine, Medical College of Qinghai University, Qinghai Xining from 1st October 2020 to 15th March 2021. Methodology: Twenty four Sprague Dawley rats were randomly divided into 4 groups; control, 24hr, 48hr, and 72hr. Hypoxia was simulated at the altitude of 7000m in an automated hypobaric hypoxia simulator. In the control and hypoxia treatment groups, the blood sample and brain tissue samples were collected. For the biochemical estimation, activities of CAT, GPx, SOD and content of MDA were evaluated. Results: A significant reduces in the activities of catalase, glutathione peroxidase and superoxide dismutase was observed when it is compared to that of the control group. Furthermore, the hypoxia treatment group had a higher content of MDA compared to that of the control group. Conclusion: Acute hypobaric hypoxia promotes oxidative stress which can cause serious damage to the brain tissues. Keywords: Hypobaric hypoxia, Oxidative stress, Brain injury, Peroxidation, Rats

Whole-Blood and Peripheral Mononuclear Cell Transcriptional Response to Prolonged Altitude Exposure in Well-Trained Runners.

Recombinant human erythropoietin (rHuEpo) abuse by athletes threatens the integrity of sport. Due to the overlap in physiological response to rHuEpo and altitude exposure, it remains difficult to differentiate changes in hematological variables caused by rHuEpo or altitude, and therefore, other molecular methods to enhance anti-doping should be explored. To identify the hematological and transcriptomic response to prolonged altitude exposure typical of practices used by elite athletes. Longitudinal study. University of Cape Town and Altitude Training Centre in Ethiopia. Fourteen well-trained athletes sojourned to an altitude training camp in Sululta, Ethiopia (∼2400-2500 m above sea level) for 27 days. Blood samples were taken before arrival, 24 hours, and 9, 16, and 24 days after arrival at altitude in addition to 24 hours and 6, 13, and 27 days upon return to sea level. Blood samples were analyzed for hemoglobin concentration, hematocrit, and reticulocyte percentage. The transcriptomic response in whole blood and peripheral blood mononuclear cells (PBMC) were analyzed using gene expression microarrays. A unique set of 29 and 10 genes were identified to be commonly expressed at every altitude time point in whole blood and PBMC, respectively. There were no genes identified upon return to sea level in whole blood, and only one gene within PBMC. The current study has identified a series of unique genes that can now be integrated with genes previously validated for rHuEpo abuse, thereby enabling the differentiation of rHuEpo from altitude exposure.

Poor Knowledge of Acute Mountain Sickness in Latin American Medical Students.

Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m). We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms. A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended. We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.

Resting-State Neuronal Activity and Functional Connectivity Changes in the Visual Cortex after High Altitude Exposure: A Longitudinal Study.

Damage to the visual cortex structures after high altitude exposure has been well clarified. However, changes in the neuronal activity and functional connectivity (FC) of the visual cortex after hypoxia/reoxygenation remain unclear. Twenty-three sea-level college students, who took part in 30 days of teaching at high altitude (4300 m), underwent routine blood tests, visual behavior tests, and magnetic resonance imaging scans before they went to high altitude (Test 1), 7 days after they returned to sea level (Test 2), as well as 3 months (Test 3) after they returned to sea level. In this study, we investigated the hematological parameters, behavioral data, and spontaneous brain activity. There were significant differences among the tests in hematological parameters and spontaneous brain activity. The hematocrit, hemoglobin concentration, and red blood cell count were significantly increased in Test 2 as compared with Tests 1 and 3. As compared with Test 1, Test 3 increased amplitudes of low-frequency fluctuations (ALFF) in the right calcarine gyrus; Tests 2 and 3 increased ALFF in the right supplementary motor cortex, increased regional homogeneity (ReHo) in the left lingual gyrus, increased the voxel-mirrored homotopic connectivity (VMHC) value in the motor cortex, and decreased FC between the left lingual gyrus and left postcentral gyrus. The color accuracy in the visual task was positively correlated with ALFF and ReHo in Test 2. Hypoxia/reoxygenation increased functional connection between the neurons within the visual cortex and the motor cortex but decreased connection between the visual cortex and motor cortex.

Sex-Specific Difference in the Effect of Altitude on Sleep and Nocturnal Breathing in Young Healthy Volunteers.

Importance: To date, there is no established evidence of sex-specific differences in altitude-induced sleep-disordered breathing (SDB) during polysomnography-confirmed sleep. Objective: The aim of this study was to investigate whether differences in sex play a pivotal role in incidences of SDB and acute mountain sickness (AMS) when staying overnight at high altitude. Design: This was a prospective cohort study. Setting: Participants underwent overnight polysomnography (PSG) and clinical assessment in a sleep laboratory at 500 m and two consecutive days at 3270 m. Participants: The participants comprised 28 (18 women) healthy, young, low-altitude residents with a median (interquartile range) age of 26.0 (25.0, 28.0) years. Exposures: Altitude exposure. Main outcomes and Measures: The primary outcome was altitude-induced change in the PSG-confirmed apnea–hypopnea index (AHI) at 3270 m compared to 500 m between men and women. Secondary outcomes included sex differences in other parameters related to SDB, sleep structure, AMS, psychomotor vigilance test reaction time and parameters from arterial and venous blood analyses. Results: The median (interquartile range) AHIs at 500 m and 3270 m on night 1 and on night 2 were 6.5/h (3.6, 9.1), 23.7/h (16.2, 42.5) and 15.2/h (11.8, 20.9) in men, respectively, and 2.2/h (1.0, 5.5), 8.0/h (5.3, 17.0) and 7.1/h (4.9, 11.5) in women, respectively (p < 0.05 nights 1 and 2 at 3270 m vs. 500 m in men and women). The median difference (95% CI) of altitude-induced change in AHI (3270 m night 1 compared to 500 m) between men and women was 11.2/h (1.9 to 19.6) (p < 0.05). Over the time course of 2 days at 3270 m, 9 out of 18 (50%) women and 1 out of 10 (10%) men developed AMS (p < 0.05 women versus men). Conclusions and Relevance: This prospective cohort study showed that men were more susceptible to altitude-induced SDB but that they had a lower AMS incidence when staying for 2 days at 3270 m than women. These findings indicate that sex-related prevention and intervention strategies against SDB and AMS are highly warranted. Trial Registration: This trial was registered at the Chinese Clinical Trial Registry; No. ChiCTR1800020155.

Respiratory responses to hypoxia during rest and exercise in individuals born pre-term: a state-of-the-art review.

The pre-term birth survival rate has increased considerably in recent decades, and research investigating the long-term effects of premature birth is growing. Moreover, altitude sojourns are increasing in popularity and are often accompanied by various levels of physical activity. Individuals born pre-term appear to exhibit altered acute ventilatory responses to hypoxia, potentially predisposing them to high-altitude illness. These impairments are likely due to the use of perinatal hyperoxia stunting the maturation of carotid body chemoreceptors, but may also be attributed to limited lung diffusion capacity and/or gas exchange inefficiency. Aerobic exercise capacity also appears to be reduced in this population. This may relate to the aforementioned respiratory impairments, or could be due to physiological limitations in pulmonary blood flow or at the exercising muscle (e.g. mitochondrial efficiency). However, surprisingly, the debilitative effects of exercise when performed at altitude do not seem to be exacerbated by premature birth. In fact, it is reasonable to speculate that pre-term birth could protect against the consequences of exercise combined with hypoxia. The mechanisms that underlie this assertion might relate to differences in oxidative stress responses or in cardiopulmonary morphology in pre-term individuals, compared to their full-term counterparts. Further research is required to elucidate the independent effects of neonatal treatment, sex differences and chronic lung disease, and to establish causality in some of the proposed mechanisms that could underlie the differences discussed throughout this review. A more in-depth understanding of the acclimatisation responses to chronic altitude exposures would also help to inform appropriate interventions in this clinical population.

Effect of Wearing the Elevation Training Mask on Physiological Performance in Elite Kayaking Girls

Background: The elevation training mask 2.0 (ETM) has been introduced as a novel tool to allow for respiratory muscle training and altitude exposure during exercise that can improve performance and hematological markers in elite and well-trained athletes. Objectives: The purpose of the present study was to examine the effect of wearing ETM while performing exercise training on erythropoietin (EPO), vascular endothelial growth factor (VEGF), peak oxygen consumption (VO2max), lactate, and 1000-m kayaking performance in elite Kayaking girls. Methods: Thirty elite Kayaking girls (14 to 18-year-old) were equally and randomly assigned into mask, no mask, and control groups. The mask and no-mask groups completed 8 weeks of repeated sprint training, while the control group performed their routine kayaking training programs. Pre- and post-training tests included EPO, VEGF, VO2max, lactate, and 1000-m kayaking performance. Results: We showed that 1000-m time trial significantly decreased for mask (P &lt; 0.001) and control (P = 0.035) groups, and was significantly lower in mask group than control (P = 0.014) and no mask (P = 0.009) groups. EPO did not show any significant changes for all groups. VEGF was increased significantly for mask (P = 0.04) and no mask (P = 0.014) groups. Lactate was decreased significantly for mask group (P = 0.025). VO2max increased significantly for no mask group (P = 0.021). Conclusions: Performing repeated sprint training while wearing ETM has the potential to enhance performance in Kayak racing.

Aberrant promoter hypermethylation regulates thrombomodulin in high altitude induced deep vein thrombosis

BackgroundDNA methylation regulates gene expression by inhibiting transcription factor binding to promoter and regulatory regions. Acute hypoxia during altitude exposure is associated with decreased natural anticoagulants and morbid thrombotic events. Thrombomodulin (TM) is a high affinity thrombin binding receptor protein, vital for vascular homeostasis. The purpose of this study is to determine gene expression regulation via methylation of TM gene in high altitude hypoxia induced deep vein thrombosis (DVT) patients. Materials and resultsPercent 5-methyl cytosine analysis showed increased methylation in high altitude DVT patients (HAP) as compared to high altitude control (HAC) and seal level control (Control) subjects, while TM protein and mRNA levels were decreased in high altitude DVT patients as compared to other two groups. Bisulfite sequencing analysis indicated increased methylation in TM promoter in high altitude DVT patients compared to high altitude controls. Flow cytometry analysis showed decreased TM expression in hypoxia induced primary human umbilical vein endothelial cells (HUVECs). Treatment with specific DNA methyltransferase (DNMT) inhibitor-decitabine during hypoxia, restored TM expression. in vitro global methylation assay showed increased methylation in hypoxia group. Specific concentration of decitabine in hypoxia decreased global methylation showing a direct correlation between DNMTs and methylation. Selective dose of decitabine restored TM levels in HUVECs. DNMT1 and DNMT3B proteins showed to mediate the overall expression of TM. ConclusionTM emerged as a potential candidate for methylation in high altitude DVT patients, regulated by hypoxia-induced epigenetic mechanism. Hypoxia culminates in methylation of DNA sequences in the promoter region of TM gene and increased the expression of DNMT1 and DNMT3B per se in primary HUVECs. Critical DNA methylation events were found to be compromised in high altitude DVT patients.

Gene Expression Changes Associated with Acute Mountain Sickness After Rapid Altitude Exposure at The South Pole

Many individuals travel to high altitude each year. Acclimatization to altitude occurs over the course of several days as the body adequately adapts to function in an environment with reduced partial pressure of oxygen. However, with a faster accent to attitude, comes an increased potential for maladaptations to occur, leading to the development of acute mountain sickness (AMS). Each year scientists and support workers are transported by plane from McMurdo Station in Antarctica (sea level) to the Amundsen‐Scott South Pole Station (2835m). This uniform and rapid deployment to altitude provides a unique opportunity to study the effects of hypobaric hypoxia on gene expression, which may help to illustrate the body’s ability to acclimatize to these environmental conditions.PurposeTo detect pathway specific gene expression changes associated with the development of AMS and help identify potential targets that may aid in the prediction of risk in the development of AMS symptoms due to rapid exposure to high altitude.MethodsVenous blood samples were collected from 53 (height 176.65±8.91cm, weight: 80.49±14.36kg) healthy subjects (38 (27 males; 11 females) that did not develop AMS and 15 (10 males; 5 females) that did develop AMS, as defined by the Lake Louis symptom questionnaire, collected at 2 different time points, with the first being at sea level and the second being after 48hr of altitude exposure). Microarray analysis was performed on the peripheral blood mononuclear cells (PBMCs) from the collected samples, and a logistic regression was performed to determine probe set association with AMS.ResultsThere was a total of 178 significant (p&lt;0.05) probe sets, with 156 of the probe sets being associated with AMS and 22 of the probe sets being associated with no AMS. The probe sets were entered into the Reactome Pathway Database (reactome.org). Pathways identified in association with AMS involved immune system pathways (interleukin signaling) and cellular responses to stimuli pathways (oxidative stress induced senescence signaling), and gene transcription pathways (mitochondrial biogenesis signaling, differentiation of hematopoietic stem cells). Interestingly, pathways identified in association with no development of AMS involved cell cycling pathways (mitotic signaling), chromatin organization pathways (chromatin modifying enzymes), metabolism pathways (utilization of ketone bodies) and the circadian clock pathway (circadian gene expression signaling).ConclusionThese findings indicate potential maladaptive responses within the immune system and mitochondrial function, may play a key role in why some individuals develop AMS symptoms. An individual’s ability to sufficiently utilize different metabolic fuel sources and adapt their circadian rhythm may also prevent the development of AMS symptoms.

Evaluation of macular and choroidal thickness in healthy residents living at high altitude.

Purpose:Assessment of long-term effects of high altitude on choroidal thickness.Methods:This prospective cross-sectional study included 88 and 79 age- and sex-matched healthy individuals who were living at sea-level (SL group) and high-altitude (HA group), respectively. Participants were required to have resided in the same place for at least 10 years. Spectral-domain optical coherence tomography (SD-OCT) scans were conducted in two different and were performed within the same time (08:00 am to 10:00 am). Central macular thickness (CMT) and choroidal thickness were measured at five different points (i.e., at the central fovea and 1 mm and 2 mm temporal and nasal of the fovea). Blood hemoglobin (Hb), red blood cell (RBC), hematocrit (Htc) levels, blood oxygen saturation, heart rate, and body mass index (BMI) were compared between groups statistically.Results:The HA group had a mean age of 47.5 ± 13.3 years, whereas the SL group was 48.7 ± 13.4 years (P = 0.57). There was no significant difference between the groups in terms of CMT. Subfoveal choroidal thickness (SCFT) was 282.73 ± 87.82 mm in the HA group and 310.49 ± 74.73 in the SL group (P = 0.02). The choroid was found to be thinner at all the measured locations in the HA group except the 2 mm nasal point of the fovea. However, only the difference at an SFCT was statistically significant. Furthermore compared with the SL group statistically significant higher Hb, RBC, Htc levels were determined in the HA group. In the multiple linear regression model analysis, age was found an only effective confounder factor for SCFT (P = 0.001, 95% CI 4.132–2.476).Conclusion:The systemic adaptive changes due to chronic high altitude exposure may cause structural changes in the choroidal vascular network. The current study results revealed significant thinning only at SFCT. Large-scale longitudinal studies are needed to obtain more definitive data on this subject.

Combined Effect of Acute Altitude Exposure and Vigorous Exercise on Platelet Activation

Exposure to high altitudes and exercise alters body's physiology and may cause acute cardiovascular events. Platelet activation is one of the key players in these events. Therefore, we investigated the effect of vigorous exercise at higher altitude (2650 m) on platelet aggregation and serum markers of platelet activation. 14 healthy subjects performed a step incremental ergometer test until exhaustion at the Environmental Research Station (UFS, 2650 m) at Zugspitze. Platelet aggregation and serum levels of endothelin-1, soluble p-selectin, platelet factor 4 and Chromogranin A were measured. Platelet activation was significantly enhanced after exercise at high altitude compared to measures immediately prior exercise. We detected significantly enhanced serum levels of endothelin-1 and soluble p-selectin whereas chromogranin A and platelet factor 4 remained unchanged. This effect might be due to increased endothelin-1 levels causing pulmonary vasoconstriction, rheological changes and direct platelet activation. This might be of clinical relevance, especially in patients with pre-existing diseases.

High Intraindividual Variability in the Response of Serum Erythropoietin to Multiple Simulated Altitude Exposures

Baranauskas, Marissa N., Timothy J. Fulton, Alyce D. Fly, Bruce J. Martin, Timothy D. Mickleborough, and Robert F. Chapman. High intraindividual variability in the response of serum erythropoietin to multiple simulated altitude exposures. High Alt Med Biol 00:000-000, 2022. Purpose: To evaluate within-subject variability in the serum erythropoietin (EPO) response to multiple simulated altitude exposures. Methods: Seven physically active men and women (age 27 ± 3 years, body mass index = 24.6 ± 4.0 kg/m2) were exposed to normobaric hypoxia (fraction of inspired oxygen [FiO2] = 0.14) for 12 hours on three separate occasions. Serum EPO concentrations were measured before exposure (0 hour), after 6 hours, and after 12 hours in hypoxia. The EPO response to hypoxia was calculated as percent change from 0 to 12 hours (ΔEPO0-12). Results: Exposure time had a significant effect on EPO (p < 0.001) with concentrations increasing 3.2 ± 1.3 mIU/ml from 0 to 6 hours (p = 0.034) and 4.7 ± 1.2 mIU/ml from 0 to 12 hours (p = 0.001). Group mean ΔEPO0-12 remained unchanged (p = 0.688) between the three exposures; however, there was considerable intraindividual variability in EPO responses. The intrasubject coefficient of variation for ΔEPO0-12 was 61% ± 28% (range: 17%-103%) with intrasubject associations ranging r = 0.052 to r = 0.651 between repeated exposures. Conclusions: Athletes who routinely supplement training with simulated altitude methods (e.g., hypoxic tents) should expect inconsistent EPO responses to intermittent exposures lasting ≤12 hours.

Dietary Nitrate Supplementation Does Not Alter Exercise Efficiency at High Altitude - Further Results From the Xtreme Alps Study.

IntroductionNitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. We hypothesized that performing exercise at high altitude would lower circulating nitrate and nitrite levels and that BRJ ingestion would reverse this phenomenon while concomitantly improving key determinants of aerobic exercise performance.MethodsTwenty seven healthy volunteers (21 male) underwent a series of exercise tests at sea level (SL, London, 75 m) and again after 5–8 days at high altitude (HA, Capanna Regina Margherita or “Margherita Hut,” 4,559 m). Using a double-blind protocol, participants were randomized to consume a beetroot/fruit juice beverage (three doses per day) with high levels of nitrate (∼0.18 mmol/kg/day) or a nitrate-depleted placebo (∼11.5 μmoles/kg/day) control drink, from 3 days prior to the exercise trials until completion. Submaximal constant work rate cycle tests were performed to determine exercise efficiency and a maximal incremental ramp exercise test was undertaken to measure aerobic capacity, using breath-by-breath pulmonary gas exchange measurements throughout. Concentrations of nitrate, nitrite and nitrosation products were quantified in plasma samples collected at 5 timepoints during the constant work rate tests. Linear mixed modeling was used to analyze data.ResultsAt both SL and HA, plasma nitrate concentrations were elevated in the nitrate supplementation group compared to placebo (P < 0.001) but did not change throughout increasing exercise work rate. Delta exercise efficiency was not altered by altitude exposure (P = 0.072) or nitrate supplementation (P = 0.836). V̇O2peak decreased by 24% at high altitude (P < 0.001) and was lower in the nitrate-supplemented group at both sea level and high altitude compared to placebo (P = 0.041). Dietary nitrate supplementation did not alter other peak exercise variables or oxygen consumption at anaerobic threshold. Circulating nitrite and S-nitrosothiol levels unexpectedly rose in a few individuals right after cessation of exercise at high altitude.ConclusionWhilst regularly consumed during an 8 days expedition to terrestrial high altitude, nitrate supplementation did not alter exercise efficiency and other exercise physiological variables, except decreasing V̇O2peak. These results and those of others question the practical utility of BRJ consumption during prolonged altitude exposure.

Global REACH 2018: Characterizing Acid-Base Balance Over 21 Days at 4,300 m in Lowlanders.

Steele, Andrew R., Philip N. Ainslie, Rachel Stone, Kaitlyn Tymko, Courtney Tymko, Connor A. Howe, David MacLeod, James D. Anholm, Christopher Gasho, and Michael M. Tymko. Global REACH 2018: characterizing acid-base balance over 21 days at 4,300 m in lowlanders. High Alt Med Biol. 23:185-191, 2022. Introduction: High altitude exposure results in hyperventilatory-induced respiratory alkalosis, followed by metabolic compensation to return arterial blood pH (pHa) toward sea level values. However, previous work has limited sample sizes, short-term exposure, and pharmacological confounders (e.g., acetazolamide). The purpose of this investigation was to characterize acid-base balance after rapid ascent to high altitude (i.e., 4,300 m) in lowlanders. We hypothesized that despite rapid bicarbonate ([HCO3-]) excretion during early acclimatization, partial respiratory alkalosis would still be apparent as reflected in elevations in pHa compared with sea level after 21 days of acclimatization to 4,300 m. Methods: In 16 (3 female) healthy volunteers not taking any medications, radial artery blood samples were collected and analyzed at sea level (150 m; Lima, Peru), and on days 1, 3, 7, 14, and 21 after rapid automobile (∼8 hours) ascent to high altitude (4,300 m; Cerro de Pasco, Peru). Results and Discussion: Although reductions in [HCO3-] occurred by day 3 (p < 0.01), they remained stable thereafter and were insufficient to fully normalize pHa back to sea level values over the subsequent 21 days (p < 0.01). These data indicate that only partial compensation for respiratory alkalosis persists throughout 21 days at 4,300 m.

Hematological and Ventilatory Responses to a 3900 M Altitude Sojourn in an Elite Wheelchair-marathoner

This case study aimed to report blood markers and resting respiratory rate (RR) oscillations at sea level, during a 5-wk 3900 m altitude sojourn, and after returning to sea level in a 36-year-old professional wheelchair marathoner. Outcome measures plasma erythropoietin (EPO) concentration, hemoglobin, reticulocytes count, erythrocytes and hematocrit as well as RR were measured upon wakening 7-weeks pre-altitude, 7-days pre-altitude, 35 hours after arrival to altitude, on days 8, 15, 21, 28 and 35 at altitude, 6 and 16 days after returning to sea level. EPO increased up to 259 % (31.6 U l-1) 35 hours upon arrival at altitude and decreased below pre-altitude level (12.2 U l-1) on the 21st day of the camp (8.7 U l-1), reaching the lowest values 16 days after returning from altitude (1.9 U l-1). All blood parameters, except for reticulocytes, increased (range: +17.9 to +23.8%) after 35 days of altitude exposure. Compared to pre-altitude, RR increased during the first week of exposure to hypoxic conditions and remained elevated throughout the camp until the fifth week (5.1±0.4 vs. 9.1±1.6 and 6.6±0.8 breaths min-1; Cohen´s d = +3.4 and +2.4, respectively). A 5-wk high-altitude sojourn triggered polycythemia and elevations in RR (as indicators of effective hypoxic acclimatization) in a professional wheelchair-marathoner.

Altitude and Endurance Performance in Altitude Natives versus Lowlanders: Insights from Professional Cycling.

Acute altitude exposure influences exercise performance, although most research, especially regarding altitude natives, comes from laboratory data in nonathletes. We analyzed the influence of altitude on real-world cycling performance in top-level professional cyclists attending to whether they were altitude natives or not. Thirty-three male cyclists (29 ± 5 yr) were studied and were classified as lowlanders (n = 19) or altitude natives (n = 14) attending to the altitude of their place of birth (431 ± 380 and 2583 ± 334 meters above sea level (m a.s.l.), respectively). Both groups included top 3 finishers (including winners) in the general classification of Grand Tours and major races. Using data from both training and competitions during years 2013-2020 (8 ± 5 seasons per cyclist), we registered participants' mean maximal power (MMP) for efforts lasting 5 s, 30 s, 5 min, and 10 min, respectively, at altitudes ranging from 0-500 to >2000 m a.s.l. A significant altitude-MMP interaction effect (two-factor repeated-measures ANOVA) was found in lowlanders (P < 0.001) but not in altitude natives (P = 0.150). In lowlanders, individual performance decreased in a dose-response manner with increasing altitudes compared with sea (or near-sea) level (0-500 m a.s.l.), whereas this trend was much less evident in natives. A significant altitude-MMP-group effect was found (P < 0.001), with nonsignificant (and overall trivial-to-small differences) between lowlanders and altitude natives for any effort duration at altitudes ≤1500 m a.s.l. but with significant differences at higher altitudes (≥1501 m a.s.l.). Acute altitude exposure influences real-world performance differently in low landers and altitude natives, which might confer a competitive advantage to the latter, particularly in races including efforts at >1500 m a.s.l.