Simulated Altitude Research Articles

Accuracy and Reliability of Commercial Wrist-Worn Pulse Oximeter During Normobaric Hypoxia Exposure Under Resting Conditions

ABSTRACT Purpose: The present study analyzed peripheral blood oxygen saturation (SpO2) and heart rate (HR) measurements taken on the Garmin fēnix® 5X Plus watch, comparing them to measurements taken on a standard medical-grade pulse oximeter during normobaric hypoxia exposure under resting conditions. Methods: Thirteen women (mean ± SD: Age 20 ± 1 years, height 165 ± 5 cm, mass, 67 ± 9 kg) and ten men (mean ± SD: Age 21 ± 3 years, height 177 ± 6 cm, mass 78 ± 11 kg) sat inside a customized environmental chamber while the fraction of inspired oxygen (FIO2) was adjusted to simulate altitudes of 12,000; 10,000; 8,000; 6,000; and 900 ft. The novel commercial device (Garmin fēnix®) and a medical-grade pulse oximeter (Nonin® 7500) were used to measure SpO2 and HR in triplicate at each simulated altitude. Bland–Altman analyses were used to assess differences between methods. Results: Bland–Altman analysis indicated 3.3% bias for SpO2 measurements taken on the Garmin fēnix® at 12,000 ft of simulated altitude (limits of agreement: −1.9–8.6%). Mean differences in SpO2 measurements were smaller at the remaining simulated altitudes, where bias measurements ranged from 0.7% to 0.8%. The Garmin fēnix® also underestimated heart rate, but those discrepancies were minimal (bias measurements at all simulated altitude exposures were < 1.0 bpm). Conclusions: With the exception of readings taken at 12,000 ft of simulated altitude, the Garmin fēnix® exhibits minimal overestimation of SpO2 and minimal underestimation of HR during simulated altitude exposure. These data suggest the Garmin fēnix® watch may be a viable method to monitor SpO2 and HR under most ambient environmental conditions.

The Separate And Combined Effects Of Acute Simulated Altitude And High Ambient Temperature On Cycling Time Trial Performance

Simulated altitude and high ambient temperature independently compromise endurance performance, although there is limited evidence on the combined exposure to both stressors. In addition, the effect of corresponding underlying key mechanisms has yet to be quantified. PURPOSE: To investigate the separate and combined effects of acute simulated altitude and high ambient temperature on time trial (TT) performance, VO2max, the ventilatory threshold (VT) and gross efficiency (GE). METHODS: Ten trained male cyclists performed 4 maximal incremental exercise tests (GXT) and GE-tests, both at sea-level (0 m; 20.93% O2) and simulated altitude (2000 m; 16.3% O2) in high environmental temperature (36.00 ± 1.4°C, 42.58 ± 0.8% RH) and temperate conditions (16.00 ± 0.32°C, 40.20 ± 1.2% RH). The GXT included 3 min at 100 W, followed by 25 W·min-1 until volitional fatigue. GE was determined at 50% of the power attained at VO2max in relative conditions, prior to and following 4000m TT performances. RESULTS: Although average PO was significantly reduced during TT performance at simulated altitude (31 ± 18 W, p<.001, n2p=.795) and high ambient temperature (9 ± 16 W, p=.007, n2p=.570), no significant interaction was found (p=.137). At simulated altitude, VO2max (3.77 ± 2.1 ml·kg-1·min-1, p<.001, n2p=.925), VT (3.39 ± 2.9 ml·kg-1·min-1, p<.001, n2p=.795) and GE (0.72 ± 0.97%, p=.021, n2p=0.555) were significantly reduced compared to sea level. However, VO2max (3.33 ± 3.1 ml·kg-1·min-1, p=.005, n2p=.608) and VT (2.05 ± 3.1 ml·kg-1·min-1, p=.021, n2p=.462) were significantly increased at high ambient temperature, although no effect on GE (p=0.240) was found. CONCLUSION: The reduction in TT performance at acute simulated altitude is associated with a decline in VO2max, VT and GE, likely because a lower SpO2. VO2max and VT are significantly higher at acute high ambient temperature, likely because the metabolic cost of physiological heat stress increases relative exercise intensity at similar absolute PO. GE was unaffected by acute high ambient temperature, likely because heat exposure during the GE-test was too short to increase Tcore. VO2max, VT and GE were not compromised during combined exposure, which corresponds with the absence of a significant interaction effect in endurance performance.

Effects Of Elevation Training Mask In Conjunction With High Intensity Interval Training On Lung Function

A recent training tool, the elevation training mask (ETM) is a commercially available simulated altitude training device with claims to increase lung function and aerobic capacity by incorporating valves to create respiration resistance. Previous studies have resulted in conflicting conclusion regarding the effectiveness of the ETM with respect to lung function. PURPOSE: To compare the effects of the ETM in conjunction with high intensity interval training (HIIT) and HIIT alone (i.e., using mask with no resistance) on lung function. METHODS: Sixteen healthy adults (control group, n=8 & experimental group, n=8) participated in this study. Pre- and post-test consisted of lung function (FEV1 & FVC) using spirometer, time to exhaustion (TTE) using the Bruce protocol on treadmill, and body mass index (BMI). Training was completed on a cycle ergometer on 3 nonconsecutive days per week (MWF), for 4 wks. Participants exercised at 85% of HRmax, using heart rate monitor, with a pedal rate of 100-120 rpm at individually set resistance levels. Each training session consisted of 10 bouts of 30s exercise followed by 30s of active recovery for a total time of 10 min. The respiratory resistance on the ETM for the experimental group was progressively increased from 915.4 m- 2,743.2 m (3,000 ft-9,000 ft.) during wks of training, while the control group used ETM with no resistance. RESULTS: Following training, a significant difference in FVC between the groups was found (F (1, 4) = 7.486, p = 0.016). In addition, no significant (p > 0.05) differences between the groups in FEV1 (experimental: 3.78 ± 0.94L; control: 3.83 ± 0.59L), TTE (experimental: 11:30 ± 1.92min; control: 12:23 ± 1.60min) and BMI (experimental: 23.01 ± 3.24kg/m2; control: 24.25 ± 2.97kg/m2) was noted. However, the experimental group yielded a greater increase in FEV1 compared to the control group (experimental: 3.40%; control: 2.42%). CONCLUSION: In the present study, the ETM resulted in a small increase in FEV1 and significantly improved FVC more than HIIT alone. Using the ETM in conjunction with HIIT may significantly improve lung function compared to HIIT only. When used in conjunction with HIIT, the ETM appears to create sufficient resistance to strengthen the muscles in respiratory ventilation and improve respiratory efficiency.

A Focused Review on the Maximal Exercise Responses in Hypo- and Normobaric Hypoxia: Divergent Oxygen Uptake and Ventilation Responses.

The literature suggests that acute hypobaric (HH) and normobaric (NH) hypoxia exposure elicits different physiological responses. Only limited information is available on whether maximal cardiorespiratory exercise test outcomes, performed on either the treadmill or the cycle ergometer, are affected differently by NH and HH. A focused literature review was performed to identify relevant studies reporting cardiorespiratory responses in well-trained male athletes (individuals with a maximal oxygen uptake, VO2max > 50 mL/min/kg at sea level) to cycling or treadmill running in simulated acute HH or NH. Twenty-one studies were selected. The exercise tests in these studies were performed in HH (n = 90) or NH (n = 151) conditions, on a bicycle ergometer (n = 178) or on a treadmill (n = 63). Altitudes (simulated and terrestrial) varied between 2182 and 5400 m. Analyses (based on weighted group means) revealed that the decline in VO2max per 1000 m gain in altitude was more pronounced in acute NH vs. HH (−7.0 ± 1.4% vs. −5.6 ± 0.9%). Maximal minute ventilation (VEmax) increased in acute HH but decreased in NH with increasing simulated altitude (+1.9 ± 0.9% vs. −1.4 ± 1.8% per 1000 m gain in altitude). Treadmill running in HH caused larger decreases in arterial oxygen saturation and heart rate than ergometer cycling in acute HH, which was not the case in NH. These results indicate distinct differences between maximal cardiorespiratory responses to cycling and treadmill running in acute NH or HH. Such differences should be considered when interpreting exercise test results and/or monitoring athletic training.

Relationships Between Ventilatory And Heart Rate Responses To Hypobaric Hypoxia: Influences Of Acetazolamide

Acetazolamide (AZ) is often used for prevention and/or treatment of acute mountain sickness (AMS), particularly during rapid ascent to altitudes > 3000 m. Although it is known that AZ augments ventilation (VE), it is unclear how this may affect chemoreflex relationships among ventilatory variables and control of heart rate (HR). PURPOSE: The purpose of the study was two-fold: 1), establish the effect of AZ and hypobaric hypoxia (HH) on VE and HR; and 2), estimate the effect of AZ on the chemoreflex relationship between VE and HR. METHODS: After completing familiarization testing at sea level (SL), 10 male volunteers (22 ± 3 yr; height: 176.0 ± 7.1 cm; weight: 77.5 ± 11.5 kg) completed two 30 hr HH exposures (~ 3500 m); one while taking AZ (500 mg/day) and one while taking a placebo, in a single-blind crossover design in random order. Ventilation and gas exchange, including HR, VE, and end-tidal partial pressure of carbon dioxide (PetCO2), were measured three times at rest, once at SL and then at ~2 and 24 hours into exposure to simulated altitude. A linear mixed model with a random intercept per subject was utilized to evaluate the influences of AZ and HH on HR, VE, and PetCO2. RESULTS: VE increased and PetCO2 decreased (p<0.05 for all) with both HH and AZ. HR increased with HH (p<0.001), but there was no further effect of AZ (p=0.15). HR was related to both VE (p=0.009) and PetCO2 (p<0.001) in all subjects. AZ shifted the relationships between HR, VE, and PetCO2, but there was no interaction between AZ and HH (p>0.10 for both). Overall, while AZ augmented VE it did not affect the slope of the relationship between HR and VE, but rather shifted the relationship to lower VE values. CONCLUSION: During exposure to HH, activation of the chemoreflex augments both ventilation and sympathetic outflow to the heart causing increased HR. Our present findings that VE tended to be lower for a given level of HR during AZ trials, suggest that AZ may have an influence to shift the relationship between these two chemoreflex-mediated events. Funded by USAMRMC; author views not official US Army or DOD policy.

Inclusion of resistance routines in a hypoxia training program does not interfere with prevention of acute mountain sickness

ABSTRACT Objectives Acclimatization strategies have been shown to be the best solutions to avoid acute mountain sickness. In this context, we have designed a protocol performed in hypoxia that includes resistance routines in combination with classical endurance training exercises with mountain trekking at mid altitude. Methods Thirty-two volunteers preparing different mountain expeditions participated in the study distributed into two groups. One group trained at 2000 m, while another group trained at 4500–5800 m of simulated altitude in a hypoxic chamber. Acute mountain sickness was monitored by answering the Lake Louise Scale questionnaire during 2 sleeping sessions at 4800 m of simulated altitude at the beginning and at the end of the study. At the same time, oxygen saturation was determined in both groups to monitor physiologic adaptation. Data were also collected from the base camps in each expedition before ascension. Results Acute mountain sickness incidence in the hypoxic group decreased from 100% at the beginning to 12% of individuals at the end of the training period, and it was 25% at the base camps of expeditions. On the other hand, the control group passed from 100% to 88% of individuals at the end of the intervention and 70% at the base camps. At the same time, acute mountain sickness severity was mild in the experimental group compared to moderate-severe in the control group. These data were supported by the oxygen saturation values, indicating adequate adaptation changes for altitude in the hypoxic group. Conclusion The inclusion of resistance workouts in combination with endurance exercises, all performed in hypoxic conditions, does not interfere with an optimal adaptation to altitude and to prevent acute mountain sickness.

Effects of leptin on HPG axis and reproductive function in male rat in simulated altitude of 5500 m hypoxia environment

High altitude hypobaric hypoxia environment impairs male’s reproductive function. Leptin is an adipose tissue-derived hormone which regulates body weight homeostasis. Its receptor (LepR) has been found in all levels of male reproductive axis, indicating that it can affect male reproductive system in a direct or (and) indirect way. However, the role of leptin signaling in hypobaric hypoxia induced male reproductive dysfunction remains to be elucidated. In this study, we investigated the changes of leptin levels in male SD rats in stimulated altitude of 5500 m hypobaric hypoxia environment and their effects on the hypothalamus-pituitary-gonad axis (HPG axis). A hypoxia animal model was established using a hypobaric hypoxia chamber. Rats were divided randomly into 1, 7, 14, 28-day hypoxia group, recovery group (14 days hypoxia+14 days normoxia) and their control groups. Hypoxia groups displayed obvious changes of testicular and epididymis index compared to control groups. The total number of sperm and sperm motility rate decreased dramatically, while sperm deformity rate increased in hypoxia groups. The flow cytometry analysis showed that the percentage of haploid in 1-day, 7-day and 28-day hypoxia groups increased while the proportion of diploid decreased in 14-day and 28-day hypoxia group. TUNEL staining showed that the testis cells apoptosis index (AI) of hypoxia groups increased significantly, and the apoptosis of cells mainly focus on spermatogonia and spermatocytes. The expression of GnRH in hypothalamus decreased dramatically under hypoxia condition, accompanied with the reduction of serum testosterone (T) level in 1-day and 28-day hypoxia groups and free-testosterone level (FT) in 1-day and 14-day hypoxia groups. Importantly, ELISA analysis showed that serum leptin level decreased in 7-day hypoxia groups and acylated-ghrelin, gastrin also changed, accompanying with reduction of LepR in hypothalamus in hypoxia groups. Immunohistochemical staining exhibited increased leptin and LepR in testis under hypobaric hypoxia conditions. Our results suggested that simulated high altitude hypobaric hypoxia environment decreased male reproductive function, depressed HPG axis activity and altered the serum concentration of hormones related to food intake in adult male rats. Additionally, hypobaric hypoxia induced the leptin-LepR expression in adult male rats’ testis, suggesting leptin-LepR signaling may mediate hypoxia-induced impairment in male rats’ reproductive system.

Acute performance and physiological responses to repeated-sprint exercise in a combined hot and hypoxic environment.

We investigated performance, energy metabolism, acid–base balance, and endocrine responses to repeated‐sprint exercise in hot and/or hypoxic environment. In a single‐blind, cross‐over study, 10 male highly trained athletes completed a repeated cycle sprint exercise (3 sets of 3 × 10‐s maximal sprints with 40‐s passive recovery) under four conditions (control [CON; 20℃, 50% rH, FiO2: 20.9%; sea level], hypoxia [HYP; 20℃, 50% rH, FiO2: 14.5%; a simulated altitude of 3,000 m], hot [HOT; 35℃, 50% rH, FiO2: 20.9%; sea level], and hot + hypoxia [HH; 35℃, 50% rH, FiO2: 14.5%; a simulated altitude of 3,000 m]). Changes in power output, muscle and skin temperatures, and respiratory oxygen uptake were measured. Peak (CON: 912 ± 26 W, 95% confidence interval [CI]: 862–962 W, HYP: 915 ± 28 W [CI: 860–970 W], HOT: 937 ± 26 W [CI: 887–987 W], HH: 937 ± 26 W [CI: 886–987 W]) and mean (CON: 808 ± 22 W [CI: 765–851 W], HYP: 810 ± 23 W [CI: 765–855 W], HOT: 825 ± 22 W [CI: 781–868 W], HH: 824 ± 25 W [CI: 776–873 W]) power outputs were significantly greater when exercising in heat conditions (HOT and HH) during the first sprint (p < .05). Heat exposure (HOT and HH) elevated muscle and skin temperatures compared to other conditions (p < .05). Oxygen uptake and arterial oxygen saturation were significantly lower in hypoxic conditions (HYP and HH) versus the other conditions (p < .05). In summary, additional heat stress when sprinting repeatedly in hypoxia improved performance (early during exercise), while maintaining low arterial oxygen saturation.

Analysis of the Honeywell Uncertified Research Engine With Ice Crystal Cloud Ingestion at Simulated Altitudes

Abstract The Honeywell Uncertified Research Engine (HURE), a research version of a turbofan engine that never entered production, was tested in the NASA Propulsion Systems Laboratory (PSL), an altitude test facility at the NASA Glenn Research Center. The PSL is a facility that is equipped with water spray bars capable of producing an ice cloud consisting of ice particles, having a controlled particle diameter and concentration in the airflow. To develop the test matrix of the HURE, the numerical asw analysis of flow and ice particle thermodynamics was performed on the compression system of the turbofan engine to predict operating conditions that could potentially result in a risk of ice accretion due to ice crystal ingestion. The goal of the test matrix was to provide operating conditions such that ice would accrete either in the fan-stator through the inlet guide vane region of the compression system or within the first stator of the high-pressure compressor. The predictive analyses were performed with the mean-line compressor flow modeling code (comdes-melt) which includes an ice particle model. The HURE engine was tested in PSL with the ice cloud over the range of operating conditions of altitude, ambient temperature, simulated flight Mach number, and fan speed with guidance from the analytical predictions. The engine was fitted with video cameras at strategic locations within the engine compression system flow path where ice was predicted to accrete in order to visually confirm ice accretion when it occurred. In addition, traditional compressor instrumentation, such as total pressure and temperature probes, static pressure taps, and metal temperature thermocouples, were installed in targeted areas where the risk of ice accretion was expected. The current research focuses on the analysis of the data that were obtained after testing the HURE engine in PSL with ice crystal ingestion. The computational method (comdes-melt) was enhanced by computing key parameters through the fan-stator at multiple spanwise locations in order to increase the fidelity with the current mean-line method. The Icing Wedge static wet-bulb temperature thresholds were applied for determining the risk of ice accretion in the fan-stator, which is thought to be an adiabatic region. At some operating conditions near the splitter–lip region, other sources of heat (non-adiabatic walls) were suspected to be the cause of accretion, and the Icing Wedge was not applied to predict accretion at that location. A simple order-of-magnitude heat transfer model was implemented into the comdes-melt code to estimate the wall temperature minimum and maximum thresholds that support ice accretion, as observed by video confirmation. The results from this model spanned the range of wall temperatures measured on a previous engine that experienced ice accretion at certain operating conditions. The goal of this study is to show that the computational process developed on earlier engine icing tests can be used to provide an icing risk assessment in adiabatic regions for other engines.

Effects of a Single Power Strength Training Session on Heart Rate Variability When Performed at Different Simulated Altitudes.

Álvarez-Herms, Jesús, Sonia Julià-Sánchez, Hannes Gatterer, Francisco Corbi, Gines Viscor, and Martin Burtscher. Effects of a single power strength training session on heart rate variability when performed at different simulated altitudes. High Alt Med Biol. 21:292-296, 2020. Background: This study assessed heart rate variability (HRV) after a single power strength training session performed at different hypoxic levels. Materials and Methods: Eight physically active subjects (31.1 ± 4.3 years; 177.6 ± 3.0 cm; 70.1 ± 5.2 kg) performed 6 bouts of 15-second continuous maximal jump exercises interspersed by 3 minutes of rest at different altitude levels (total volume of each session: 20 minutes). The normoxic hypoxia levels were FiO2 low altitude: 20.9%; moderate altitude: 16.5%; and high altitude: 13.5%. Results: Average power output during the jumps was similar for all conditions (≅3150 W). Twenty-four hours before (PRE) and 24 hours after (POST) each training session, HRV parameters (R-R, square root of the mean of the sum of differences between intervals [RMSSD], pNN50, and very low frequency, low frequency, and high frequency) were determined without resulting in significant statistical differences, neither from PRE to POST nor between conditions (p > 0.05). Conclusions: This study showed a negligible perturbation of HRV parameters 24 hours after a single power strength session up to a hypoxic level equivalent to 4000 m. Further studies are needed to determine the hypoxia-dependent threshold and intensities of training loads affecting HRV.

Lung Diffusion in a 14-Day Swimming Altitude Training Camp at 1850 Meters.

Swimming exercise at sea level causes a transient decrease in lung diffusing capacity for carbon monoxide (DLCO). The exposure to hypobaric hypoxia can affect lung gas exchange, and hypoxic pulmonary vasoconstriction may elicit pulmonary oedema. The purpose of this study is to evaluate whether there are changes in DLCO during a 14-day altitude training camp (1850 m) in elite swimmers and the acute effects of a combined training session of swimming in moderate hypoxia and 44-min cycling in acute normobaric severe hypoxia (3000 m). Participants were eight international level swimmers (5 females and 3 males; 17–24 years old; 173.5 ± 5.5 cm; 64.4 ± 5.3 kg) with a training volume of 80 km per week. The single-breath method was used to measure the changes in DLCO and functional gas exchange parameters. No changes in DLCO after a 14-day altitude training camp at 1850 m were detected but a decrease in alveolar volume (VA; 7.13 ± 1.61 vs. 6.50 ± 1.59 L; p = 0.005; d = 0.396) and an increase in the transfer coefficient of the lung for carbon monoxide (KCO; 6.23 ± 1.03 vs. 6.83 ± 1.31 mL·min−1·mmHg−1·L−1; p = 0.038; d = 0.509) after the altitude camp were observed. During the acute hypoxia combined session, there were no changes in DLCO after swimming training at 1850 m, but there was a decrease in DLCO after cycling at a simulated altitude of 3000 m (40.6 ± 10.8 vs. 36.8 ± 11.2 mL·min−1·mmHg−1; p = 0.044; d = 0.341). A training camp at moderate altitude did not alter pulmonary diffusing capacity in elite swimmers, although a cycling session at a higher simulated altitude caused a certain degree of impairment of the alveolar–capillary gas exchange.

Effects of Various Hypoxia vs Normoxia on Metabolic and Skeletal Muscle Oxygenation Function during Graded Exercise in Healthy Males

PurposeThe purpose of this study was to investigate the effect of various hypoxia vs. normoxia on metabolic and skeletal muscle oxygenation function during grated exercise and exercise performance.MethodsEleven healthy male participants (21.5 ± 2.3 years) performed graded exercise test (GXT) using cycle ergometer at sea‐level (760 mmHg) and under various hypobaric hypoxia (1,500 m simulated altitude; 634 mmHg, 3,000 m simulated altitude; 528 mmHg and 4,500 m simulated altitude; 433 mmHg) in a random order. GXT starts at 300 kg·m·min−1 (50 watts) and increases by 150 kg·m·min−1 (25 watts) every 2 minutes until exhaustion. The pedal frequency was set at 60 rpm. Metabolic parameters (peripheral capillary oxygen saturation; SPO2, heart rate; HR, minute ventilation; VE, oxygen consumption; VO2, carbon dioxide excretion; VCO2, respiratory exchange ratio; RER, oxygen pulse, and blood lactate) and skeletal muscle oxygen profiles (oxygenated hemoglobin and myoglobin; OxyHb, deoxygenated hemoglobin and myoglobin; DeoxyHb, and tissue oxygen saturation; StO2) were measured every 1 minute during the GXT, and it also evaluated at exercise load of 50, 75, 100, 125, and 150 watts on ergometers under various hypoxia vs. normoxia. Exercise performance was evaluated by maximal oxygen consumption, peak power, and exercise time obtained through GXT.ResultsIn metabolic parameters, HR, VE, VCO2, RER, and blood lactate showed a significant increase in hypoxia compared with normoxia. Also, the increase was more pronounced as the hypoxia became more severe. However, SPO2, VO2, and O2pulse presented a significant decrease in hypoxia compared with normoxia. Also, the decrease was more pronounced as the hypoxia became more severe. In skeletal muscle oxygen profiles, OxyHb showed a significant decrease in 3,000 m and 4,500 m simulated altitude compared with normoxia. In exercise performance, VO2max and peak power were significantly decreased in 3,000 m and 4,500 m simulated altitude compared with normoxia, and exercise time decreased significantly with increasing simulated altitude.ConclusionThese showed a decrease in exercise performance due to a decrease in metabolic parameters and skeletal muscle oxygenation in hypoxia vs. normoxia, and more pronounced as the hypoxia became more severe.Support or Funding Information

Increased Oxygen Hemoglobin Affinity Mitigates Hypobaric Hypoxia‐dependent Spatial Learning Decrements In Sprague‐Dawley Rats

IntroductionHigh altitude (HA) exposure negatively impairs cognitive performance in humans. Mechanisms for cognitive impairment include hypobaric hypoxia itself, sleep disturbance, and/or the effects of acclimation such as hyperventilation and increased red cell mass. GBT1118 (GBT) allosterically modifies Hemoglobin (Hb) and affects an increase in oxygen (O2) affinity. Using Sprague‐Dawley (SD) rats, we examined the effects of GBT1118 on spatial memory decrements observed with simulated altitude exposure.MethodsMale SD rats (N=42) underwent 4 Morris Water Maze (MWM) training sessions twice daily over a two day period, with each session including an initial platform‐acquisition followed by three platform re‐acquisitions. Once animals satisfied the initial training, they underwent MWM testing on the third day where initial and subsequent platform acquisitions were again performed collecting time and distance. On the third experimental day animals were randomized to receive GBT1118 100mg/kg by oral gavage or equal volume of saline (control). Two hours after gavage, animals were placed in a chamber and either remained at sea level (SL) or exposed to a simulated altitude of 24,000 ft. for 4 hr. Chambers were constantly flushed with air to maintain CO2 levels of &lt;0.5%. After the 4hr exposure, the chamber pressure was gradually returned to SL by allowing a pre‐mixed hypoxic gas consisting of 8.5% O2 (balance N2) into the chamber, allowing the altitude equivalent partial pressure of O2 to be maintained during descent. Once SL was reached, the animals were removed and placed into a box flushed with 8.5% O2 and then transported for MWM testing. Animals then immediately underwent MWM as previously described, except that they returned to the hypoxic box between re‐acquisition trials. Animals that were exposed to SL for 4hr were maintained in normal room air throughout testing. After MWM testing completion, the animals were anesthetized and underwent an assessment of O2‐Hb affinity by tail vein blood sample and measuring p50.ResultsO2‐Hb affinity as measured by p50 in animals treated with saline was 42.3 in SL‐exposed animals vs. 48.2 in HA‐exposed animals. GBT significantly decreased p50 to 30.4 in SL‐exposed animals compared to saline controls (p=0.0119), and to 39.1 in HA‐exposed animals compared to saline controls (p=0.0421). Spatial learning was assessed by determining the average distance and latency to the platform during the three reacquisition trials, and comparing between groups the percent change of those values from the pre‐exposure assessment and the post‐exposure assessment. Data show that, compared to SL control animals, exposure to HA significantly increases both distance (p=0.0067) and latency (p=0.0079) to find the platform. While GBT only exhibited a strong trend for mitigation of the effects of HA on distance (p=0.0566), it did significantly reduce latency (p=0.0298) compared to HA‐exposed, saline treated animals. GBT had no effect on distance or latency in SL‐exposed animals.ConclusionIncreasing O2‐Hb affinity with GBT1118 improves spatial learning in rodents exposed to HA.

Pilates Exercise in Hypoxia Increases Vascular Endothelial Function in Professional Pilates Players

PurposeThe purpose of this study was to investigate the pilates exercise in hypoxia increases vascular endothelial function in professional Pilates players.MethodsTen healthy Pilates expert female (age: 26.9 ± 2.7, weight: 50.8 ± 5.2, BMI: 19.3 ± 1.4) completed two different trials on different days, consisting of exercise in normoxia (N trial) and exercise in 3,000 m simulated altitude (526 mmHg) hypobaric hypoxia (H trial). After 30 minutes of exposure in each environment, they performed tubing Pilates exercise for 50 minutes under normoxia and hypoxia. Pilates exercise using tubing were composed of 25 types, each performed for 2 minutes. Pilates motion is configured as follows : roll up &amp; down, biceps, arm circles, teaser, rolling, spine twist, mermaid, cobra, swimming, double kicks, swan, cat, thigh stretching, hug a tree, squat, row, saw, hip pull, hundred, lats pull, leg arc, scissor, helicopter, right side leg pull, left side leg pull. Metabolic parameters (minute ventilation; VE, oxygen uptake; VO2, carbon dioxide excretion; VCO2, respiratory exchange ratio; RER, carbohydrate oxidation; CO, fatty acid oxidation; FAO, energy expenditure; EE) and cardiac function (heart rate; HR, stroke volume; SV, cardiac output; CO, end‐diastolic volume; EDV, end‐systolic volume; ESV, ejection fraction; EF) were measured every minutes during Pilates exercise. The sum of the values measured for 50 minutes was used as the result (exceptionally, RER uses average values). Blood pressure (BP), branchial ankle pulse wave velocity (baPWV) and flow mediated dilation (FMD) in branchial artery were measured as vascular function before and after exercise.ResultsIn metabolic parameters, H trial showed significantly higher VE, VCO2, RER and CO than N trial. However, FAO was lower in H trial than in N trial. VO2 and EE. VO2 and EE presented no significant difference between the two trials. In cardiac function, HR showed a significant increase in H trial compared with N trial, however, the remaining cardiac function parameters did not show significant difference. In vascular function, BP (systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure) and baPWV did not show significant interaction effects between exercise and environment. However, FMD presented a significant interaction effects between exercise and environment. As a result of the post‐hoc, both trial showed a significant increase in FMD via exercise and the increase rate in FMD was significantly higher in H trial (48.5 ± 22.9) than in N trial (34.9 ± 18.3). Also, H trial showed a significantly higher FMD before exercise than N trial.ConclusionOur results suggest that Pilates exercise under moderate hypoxia shows greater metabolic and cardiac response by relatively higher exercise intensity, and it also elicit synergy effect on vascular endothelial function than under normoxia in professional Pilates players.

Tibetan and Han Chinese oxygen transport at 2200 m and simulated 4200 m during peak exercise

Despite lower Hb concentration, Tibetans resident at 4200m exhibit greater exercise capacity than do Han Chinese also resident at 4200m. Whether these adaptations are maintained at intermediate altitude and/or acute hypobaric hypoxia are unknown.Thirty‐seven healthy, non‐smoking subjects, all resident for at least six months at ~2200 m, of Tibetan (NMale = 10; NFemale = 9) or Han Chinese (NMale = 8; NFemale = 10) ancestries were studied at 2200 m and then during acutely simulated altitude (4200 m in a hypobaric chamber). Subjects performed an incremental cycle test to exhaustion. At peak exercise, oxygen consumption (VO2max), cardiac output (QTmax), ventilation (VE), hemoglobin ([Hb]), blood oxygen saturation (SaO2), and arterial blood gases were measured and diffusing capacity in lung (DL) and muscle (DM) were calculated.At peak exercise at 2200 m, Tibetan males had 1.23 g/dL less [Hb] compared to their Han Chinese male counterparts (p = 0.03). Tibetan females had 1.05 g/dL less [Hb] then Han Chinese females, but the result is not statistically significant (p = 0.064)Compared to Han Chinese, Tibetan females tended to have 4.85 and 2.72 mLmin−1Kg−1 higher VO2max at 2200 m and 4200 m (both p = 0.03). For males, Tibetans tended to have 6.90 and 2.78 mLmin−1Kg−1 higher VO2max than Han Chinese. However, the difference in VO2max was not significant in males at 2200 m or 4200 m (p = 0.095, p = 0.306, respectively).Tibetan males, but not females, had a significantly higher lung O2 diffusing capacity (DL) compared to Han Chinese (p = 0.028 for males; p = 0.192 for females). Tibetans also tended to have increased muscle O2 diffusing capacity (DM), but the difference was not statistically significant.Tibetan compared to Han Chinese females exhibited higher VE during maximal exercise at both 2200 m and 4200 m (p &lt; 0.03, p &lt; 0.02, respectively). The differences were not significant in males (p &gt; 0.54 for 2200 m, p &gt; 0.20 for 4200 m).In addition, Tibetans had 0.53 g/dL higher carboxyhemoglobin compared to Han Chinese at 2200 m (p = 0.005) independent of sex. Considering Tibetans had lower [Hb] than Han Chinese, higher CO content might suggest increased red blood cell destruction in Tibetans.In summary, among Tibetans, who exhibit significantly lower [Hb] and elevated COHb, females exhibit increased exercise capacity and ventilation compared to Han Chinese females at 2200m, and similar trends were exhibited in males acutely exposed to simulated 4200 m. Male Tibetans exhibited greater DL than Han Chinese counterparts. Trends were further noted for greater QT and DM in Tibetans, which is consistent with our previous studies of Tibetans residents at 4200 m. Therefore, it is evident that unique traits of high‐altitude adaptation of Tibetans are retained at intermediate altitude. Such differences between hypoxic‐exercise responses of Tibetans and Han Chinese are likely innate and may be attributed to genetics.Table 1

Tibetans and Han Chinese residents at intermediate altitude respond differently to chronic and simulated altitude‐induced hypoxia

It has previously been shown that Tibetans residents at high altitude (&gt; 4000m), have higher resting ventilation, lower heart rate, and higher blood‐oxygen saturation compared to Han Chinese residents at the same altitude. However, the extent to which these findings are due to differences in acclimatization versus innate variation between populations is unclear.Thirty‐seven healthy, non‐smoking subjects, all resident at intermediate altitude (2200m) were studied. The subjects were of Tibetan (NMale = 10; NFemale = 9) and Han Chinese (NMale = 8; NFemale = 10) ancestries between ages of twenty to twenty‐five. The study was carried out under ambient conditions at 2200m and during acutely simulated altitude at 4200m in a hypobaric chamber. For each subject at rest, oxygen consumption (VO2), heart rate (HR), ventilation (VE), hemoglobin concentration ([Hb]), blood oxygen saturation (SaO2), and arterial blood gases were measured at both altitudes.Tibetans males, compared to Han Chinese, tend to have 1.2 g/dl lower [Hb] at 4200 m and 0.89 g/dl lower [Hb] at 2200 m. However, the difference is only significant at 2200 m (p = 0.036), and no difference in [Hb] is found in females.At 2200 m, Tibetan males have significantly lower resting heart rate compared to Han Chinese males (p = 0.0062). At 4200 m, this difference persists: both Tibetan males and females have lower resting heart rates than their Han Chinese counterparts (p = 0.042, p = 0.043).At both 2200 m and 4200 m, Tibetan females tend to have significantly higher VO2 (both p = 0.043), higher VCO2 (p = 0.027, p = 0.033) and higher VE (p = 0.018, p = 0.019) compared to Han Chinese females, suggesting increased ventilation. In males, no differences in VO2 or VCO2 were observed at 2200 m and 4200 m, and Tibetan males tend to have higher VE only at 4200 m, though the result is not statistically significant (p = 0.12).At 2200 m, there is no difference of SaO2 between Tibetans and Han Chinese; all groups have SaO2 well above ninety percent. However, the difference of SaO2 is more pronounced at 4200 m. Both Tibetan males and females have higher SaO2 compared to Han Chinese, although the result is only significant in the males (p = 0.045) and exhibits a trend in females (p = 0.15).In conclusion, Tibetans, whose ancestors lived at ~4200m, retain certain physiological traits when resident at 2200m. These include lower resting [Hb], higher VO2, VCO2 and VE. When acutely exposed to altitude‐induced hypoxia, Tibetans tend to maintain higher resting SaO2 and VO2. Therefore, the differences we found between Tibetans and Han Chinese are likely due more to innate differences, such as genetic and epigenetic programs.Table 1

Systemic Blood Pressure Variation During a 12-Hour Exposure to Normobaric Hypoxia (4500 m).

This study was aimed at evaluating a potential association between blood pressure variation and acute mountain sickness (AMS) during acute exposure to normobaric hypoxia. A total of 77 healthy subjects (43 males, 34 females) were exposed to a simulated altitude of 4500 m for 12 hours. Peripheral oxygen saturation, heart rate, systemic blood pressure, and Lake Louise AMS scores were recorded before and during (30 minutes, 3, 6, 9, and 12 hours) hypoxic exposure. Blood pressure dips were observed at 3-hour mark. However, systolic blood pressure fell more pronounced from baseline during the initial 30 minutes in normobaric hypoxia (-17.5 vs. -11.0 mmHg, p = 0.01) in subjects suffering from AMS (AMS+; n = 56) than in those remaining unaffected from AMS (AMS-; n = 21); values did not differ between groups over the subsequent time course. Our data may suggest a transient autonomic dysfunction resulting in a more pronounced blood pressure drop during initial hypoxic exposure in AMS+ compared with AMS- subjects.

Assessment of portable oxygen concentrators in infants undergoing hypoxic challenge testing. A randomised controlled crossover trial.

Due to reduced PaO2 , aircrafts at cruising altitudes are pressurised to a cabin altitude of 2438m, equivalent to breathing FiO2 0.15. Portable oxygen concentrators (POCs) are approved for onboard oxygen supply with lack of evidence, especially in infants. We assessed POCs (continuous-flow cPOC vs. pulsed-flow pPOC) under simulated altitude conditions performing Hypoxic Challenge Testing (HCT). In a randomised controlled crossover trial, we included patients <1year born prematurely. In incidents of hypoxia (SpO2 ≤85%), oxygen was administered through POC. In patients with a positive hypoxia reversal, HCT was repeated 24hours later. If hypoxia occurred during the second testing, oxygen was given using the alternative POC. We randomised 26 patients; 22 patients received allocated intervention (4 dropped out). Mean gestational age 30.4weeks, mean corrected age 38.2weeks. Both POCs achieved immediate hypoxia reversal in all cases (SpO2 cPOC/pPOC 98%/99.4% (95%CI -2.91, 0.01)) without any adverse events. No significant difference was observed in patients with BPD. Both POCs generated sufficient oxygen to reverse HCT induced hypoxia. Although pPOCs are not recommended in paediatric age, our data suggest their effectiveness even in neonates without any associated adverse events. Future research on pPOCs safety is required to establish recommendations for their use.

Influence of Acetazolamide on Hand Strength and Manual Dexterity During a 30-h Simulated High Altitude Exposure.

High altitude missions pose significant challenges to Warfighter medical readiness and performance. Decreased circulating oxygen levels cause a decrease in exercise performance and can cause debilitating symptoms associated with acute mountain sickness, especially with rapid ascent. Acetazolamide (AZ) is known to minimize symptoms of acute mountain sickness, but it is unknown whether this medication alters hand strength and manual dexterity during altitude exposure. Ten male volunteers (22±4yr, 75.9±13.7kg, 174.9±9.3cm) participated in two separate 30h simulated altitude exposures (496mmHg, equivalent to 3,500m, 20°C, 20% RH) in a hypobaric chamber. Participants were given either a placebo or 250mg of AZ twice daily for 3.5d (2 sea-level [SL] days + the 30h altitude exposure) in a randomized, single-blind, crossover design. During SL and both altitude (ALT) exposures, hand function tests were performed, including hand grip and finger pinch strength tests, as well as the Purdue Pegboard (PP) and magazine loading tests to assess manual dexterity. Paired T tests and two-way repeated measure analysis of variance were used as appropriate to evaluate the effects of AZ and ALT. The value of p<0.05 was accepted for statistical significance. There were no influences of acute ALT exposure or AZ treatment on hand strength (eg, grip strength; SL: 39.2±5.5kg vs. ALT: 41.5±6.9kg, p>0.05) or dexterity (eg, PPassembly; placebo: 35.5±5.3 vs. AZ: 34.3±4.6, p>0.05) in our volunteers. Two dexterity tests (PPsum and magazine loading) showed improvements over time at ALT, regardless of treatment, where scores were improved after 10h of exposure compared to at 1h (eg, magazine loading: 56±12 vs. 48±10, p<0.001). This pattern was not seen in the PPassembly test or any strength measurements. Our results suggest that 500mg/d of AZ does not influence hand strength or manual dexterity during a 30h exposure to 3,500m simulated ALT. Acute ALT exposure (1h) did not influence dexterity or strength, although some measures of dexterity showed improvements as exposure time increased. We conclude that use of AZ to optimize medical readiness at ALT is unlikely to impair the Warfighter's ability to complete mission tasks that depend on hand function.

Effect of pre-term birth on oxidative stress responses to normoxic and hypoxic exercise

Pre-term birth is a major health concern that occurs in approximately 10% of births worldwide. Despite high incidence rate, long-term consequences of pre-term birth remain unclear. Recent evidence suggests that elevated oxidative stress observed in pre-term born infants could persist into adulthood. Given that oxidative stress is known to play an important role in response to physical activity and hypoxia, we investigated whether oxidative stress responses to acute exercise in normoxia and hypoxia may be differently modulated in pre-term vs. full-term born adults. Twenty-two pre-term born and fifteen age-matched full-term born controls performed maximal incremental cycling tests in both normoxia (FiO2: 0.21) and normobaric hypoxia (FiO2: 0.13; simulated altitude of 3800 m) in blinded and randomized manner. Plasma levels of oxidative stress (advanced oxidation protein products [AOPP] and malondialdehyde), antioxidant (ferric reducing antioxidant power, glutathione peroxidase, catalase [CAT] and superoxide dismutase [SOD]) and nitrosative stress markers (nitrotyrosine, nitrite and total nitrite and nitrate [NOx]) were measured before and immediately after each test. AOPP (+24%, P<0.001), CAT (+38%, P<0.001) and SOD (+12%, P=0.018) and NOx (+17%, P=0.024) significantly increased in response to exercise independently of condition and birth status. No difference in response to acute exercise in normoxia was noted between pre-term and full-term born adults in any of measured markers. Hypoxic exposure during exercise resulted in significant increase in AOPP (+45%, P=0.008), CAT (+55%, P=0.019) and a trend for an increase in nitrite/nitrate content (+35%, P=0.107) only in full-term and not pre-term born individuals. These results suggest that prematurely born adult individuals exhibit higher resistance to oxidative stress response to exercise in hypoxia.