Simulated Altitude Research Articles

AUTHOR REPLY

We appreciate and thank the authors for their editorial comments. Dr. Cockett was a consummate academician and teacher, as well as a tireless leader in organized urology. During his career, he studied a wide assortment of urologic problems with space travel, including urolithiasis, spermatogenesis, and voiding function in weightless environments. He identified spermatogenic arrest in primates both in space flight and immobilization. 1 Cockett AT Adey WR Roberts AP Urological considerations in space medicine. Aerosp Med. 1972; 43: 258-262 PubMed Google Scholar Caliber and uroflow did not change in Air Force personnel studied during parabolic flights simulating weightlessness when compared to ground level voiding curves. 2 Cockett AT Bors E. The influence of simulated altitude (18, 000 feet) on uroflowmetry. Urol Int. 1964; 18: 357-361 Crossref PubMed Scopus (4) Google Scholar His forward thinking was evident with his work on “Protective Effects of Hypothermia in Exploration of Space” in 1962, which was most recently cited in 2019. 3 Cockett TK Beehler CC. Protective effects of hypothermia in exploration of space. JAMA. 1962; 182: 977-979 Crossref PubMed Scopus (6) Google Scholar ,4 Nordeen CA Martin SL. Engineering human stasis for long-duration spaceflight. Physiology. 2019; 34: 101-111 Crossref PubMed Scopus (15) Google Scholar

Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans.

Key points High altitude‐induced hypoxia in humans evokes a pattern of breathing known as periodic breathing (PB), in which the regular oscillations corresponding to rhythmic expiration and inspiration are modulated by slow periodic oscillations.The phase coherence between instantaneous heart rate and respiration is shown to increase significantly at the frequency of periodic breathing during acute and sustained normobaric and hypobaric hypoxia.It is also shown that polymorphism in specific genes, NOTCH4 and CAT, is significantly correlated with this coherence, and thus with the incidence of PB.Differences in phase shifts between blood flow signals and respiratory and PB oscillations clearly demonstrate contrasting origins of the mechanisms underlying normal respiration and PB.These novel findings provide a better understanding of both the genetic and the physiological mechanisms responsible for respiratory control during hypoxia at altitude, by linking genetic factors with cardiovascular dynamics, as evaluated by phase coherence. Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by low‐frequency periodic alternation between hyperventilation and apnoea. In hypoxia‐induced PB the dynamics and coherence between heart rate and respiration and their relationship to underlying genetic factors is still poorly understood. The aim of this study was to investigate, through novel usage of time–frequency analysis methods, the dynamics of hypoxia‐induced PB in healthy individuals genotyped for a selection of antioxidative and neurodevelopmental genes. Breathing, ECG and microvascular blood flow were simultaneously monitored for 30 min in 22 healthy males. The same measurements were repeated under normoxic and hypoxic (normobaric (NH) and hypobaric (HH)) conditions, at real and simulated altitudes of up to 3800 m. Wavelet phase coherence and phase difference around the frequency of breathing (approximately 0.3 Hz) and around the frequency of PB (approximately 0.06 Hz) were evaluated. Subjects were genotyped for common functional polymorphisms in antioxidative and neurodevelopmental genes. During hypoxia, PB resulted in increased cardiorespiratory coherence at the PB frequency. This coherence was significantly higher in subjects with NOTCH4 polymorphism, and significantly lower in those with CAT polymorphism (HH only). Study of the phase shifts clearly indicates that the physiological mechanism of PB is different from that of the normal respiratory cycle. The results illustrate the power of time‐evolving oscillatory analysis content in obtaining important insight into high altitude physiology. In particular, it provides further evidence for a genetic predisposition to PB and may partly explain the heterogeneity in the hypoxic response.

Early Postnatal Hypoxia Induces Behavioral Deficits but not Morphological Damage in the Hippocampus in Adolescent Rats

Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes. Subsequently, the rats underwent behavioral testing on PND25 and PND35 using a LABORAS apparatus to assess spontaneous behavior. Hypoxia did not cause any morphological damage in the hippocampus of rats. However, hypoxia on PND7 led to less horizontal locomotor activity both, in males (on PND25) and females (on PND35). Hypoxia on PND9 led to higher rearing in females on PND25. Hypoxic males exhibited higher grooming activity, while females lower grooming activity on PND35 following hypoxia induced on PND7. In females, hypoxia on PND9 resulted in higher grooming activity on PND25. Sex differences in the effect of hypoxia was observed on PND35, when hypoxic males compared to hypoxic females displayed more locomotor, rearing and grooming activity. Our data suggest that hypoxia on PND7 versus PND9 differentially affects locomotion and grooming later in adolescence and these effects are sex-dependent.

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

Hypoxic Training Is Beneficial in Elite Athletes.

There is no doubt that many hypoxic conditions or prolonged exposures to altitude result in “biological costs of hypoxic adaptations that outweigh their benefits” (1), particularly in endurance athletes exposed to a) exercise-induced arterial hypoxemia leading to a larger decrease in VO2max and aerobic endurance; b) increased sympathetic activity and decreased baroreflex sensitivity; and c) increased pulmonary arterial pressure. There is also no doubt that sleeping in moderate altitude (2000-3000 m) as performed by the athletes using either live high-train high (LHTH) or live high-train low (LHTL) methods leads to periodic breathing, intermittent hypoxia (IH) and increase in desaturation periods; e.g. 3% oxygen desaturation index, but to a larger extent in hypobaric hypoxia (HH, real altitude) than in normobaric hypoxia (NH, simulated altitude), as shown at 2250 m (2). The three main questions debated in the present contrasting perspective are however different: 1. Are there any evidences showing if the “counteracting maladaptation” (reported above) outweigh the benefits of the different hypoxic methods at short- or long-term in elite athletes? ; 2. Are there any robust data supporting that hypoxic training is beneficial in elite athletes? ; 3. Contradictory, are there robust data showing that hypoxic training is not beneficial in elite athletes?

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway.

Chronic hypoxia (CH) is characterized by long-term hypoxia that is associated with microvessel proliferation and basal membrane (BM) degradation in tissues. The IL-6/JAK2/STAT3/MMP-9 pathway has been described in a variety of human cancers and plays an essential role in microvessel proliferation and BM degradation. Therefore, this study investigated the role of the IL-6/JAK2/STAT3/MMP-9 pathway in hypoxia-mediated microvessel proliferation and BM degradation in the rat bone marrow. Eighty pathogen-free Sprague Dawley male rats were randomly divided into four groups (20 per group)—control group, CH group (exposed to hypoxia in a hypobaric chamber at a simulated altitude of 5000 m for 28 d), CH + STAT3 inhibitor group (7.5 mg/kg/d), and CH + DMSO group. Microvessel density (MVD) and BM degradation in the bone marrow were determined by immunofluorescence staining and transmission electron microscopy. Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA), and the levels of P-JAK2, P-STAT3, and MMP-9 were assessed by western blot analysis and real-time reverse transcription PCR (RT-PCR). Hypoxia increased serum IL-6 levels, which in turn increased JAK2 and STAT3 phosphorylation, which subsequently upregulated MMP-9. Overexpression of MMP-9 significantly promoted the elevation of MVD and BM degradation. Inhibition of STAT3 using an inhibitor, SH-4-54, significantly downregulated MMP-9 expression and decreased MVD and BM degradation. Surprisingly, STAT3 inhibition also decreased serum IL-6 levels and JAK2 phosphorylation. Our results suggest that the IL-6/JAK2/STAT3/MMP-9 pathway might be related to CH-induced microvessel proliferation and BM degradation in the bone marrow.

Influence of altitude on matching characteristic of electronic-controlled pneumatic two-stage turbocharging system with diesel engine

Two-stage turbocharging technology is a solution to reduce turbo lag and improve the performance of engine and matching characteristics at high altitudes. In the present study, an engine testing system was established to study combustion performance and matching characteristics of a regulated two-stage turbocharging system (R2S) at different simulated altitudes. An equivalent turbocharger concept was put forward aiming to simplify the R2S with three bypass valves, and the total equivalent turbine flow area and equivalent efficiency of the R2S were obtained based on a theoretical study. Intake characteristics, combustion process, torque, power and fuel economy of the diesel engine matched with R2S were analyzed at different altitudes. The results showed that compared with 0 m, intake pressure, maximum combustion pressure, cumulative heat release, heat release rate decreased by 36.5%, 33.6%, 33.5%, 21.6%, −8.9% at 4000 r/min, and decreased by 12.3%, 2.9%, 16.4%, 8.8%, −5.4% at the speed of 2000 r/min at the altitude of 5000 m. The torque, fuel consumption and fuel consumption rate decreased by 10.1%, 5.1% and 5.4% at engine speed of 2000 r/min and by 35.7%, 27.6% and 8.9% at engine speed of 4000 r/min at 5000 m.

Hypoxia induces an increase in intestinal permeability and pulmonary arterial pressures in neonatal Holstein calves despite feeding the flavonoid rutin

The purposes of this study were to determine whether the naturally occurring flavonoid quercetin, as its glucorhamnoside rutin, reduces intestinal permeability and susceptibility to hypoxia-induced pulmonary hypertension in neonatal Holstein calves. A 2 × 2 between-subjects factorial design was conducted using Holstein steers (n = 16). Factors included oxygen level (simulated altitude of 4,572 m vs. 975 m) and quercetin supplementation as its glucorhamnoside rutin (4 g of quercetin per day vs. 0 g per day). Two days after arrival (d 0 of study) the calves were blocked by body mass into treatment groups, and treatments were initiated. Pulmonary arterial pressure, echocardiography, and serum concentrations of orally administered lactulose (0.45 g/kg) and mannitol (0.15 g/kg) were measured on d 12, 13, and 14, respectively. Calves were euthanized on d 15 and pulmonary tissues collected for semiquantitative scoring of histological lesions. Data were analyzed using linear regression, generalized estimating equations, and 2-sample proportion tests. Hypoxia, but not rutin, was found to be associated with intestinal permeability. The lactulose-mannitol ratio was 0.54 ± 0.13 (standard error) in hypoxic calves and 0.02 ± 0.13 in normoxic controls. Hypoxia increased mean pulmonary arterial pressure. Calves fed rutin under hypoxic conditions tended to have a lower mean pulmonary arterial pressure (59 ± 7 mmHg) than control calves (80 ± 7 mmHg) but similar pressures under normoxic conditions. Paradoxically, however, a greater proportion of calves fed rutin had histological evidence of pulmonary arteriolar medial hypertrophy and adventitial hyperplasia than did controls. In conclusion, the findings of this study indicate that hypoxia increased intestinal permeability in neonatal calves. The flavonoid quercetin, as its glucorhamnoside rutin, had no protective effect on intestinal permeability, and, although it tended to reduce the severity of hypoxia-induced pulmonary hypertension, a greater proportion of calves fed rutin had histological lesions consistent with pulmonary arteriolar remodeling.

Cardiorespiratory and Metabolic Responses During Graded Exercise in Normobaric and Hypobaric Hypoxia.

Background: The study investigated submaximal exercise responses during an acute exposure to normobaric hypoxia (NH) versus hypobaric hypoxia (HH) focusing on different exercise intensities. Methods: Eight recreationally trained male subjects (age 23 ± 3 years) performed submaximal cycling exercise at three different intensity levels (100, 150, and 200 W) in NH (simulated altitude 3150 m) and HH (terrestrial high altitude, 3150 m) in a cross-over study design. Cardiorespiratory parameter, blood lactate concentration, and ratings of perceived exertion were determined at each intensity level. Results: Cardiorespiratory parameters, arterial oxygen saturation, and ratings of perceived exertion did not differ between NH and HH except for the higher ventilatory equivalent for oxygen in HH compared to NH (25.9 ± 1.3 vs. 24.6 ± 1.0 at 100 W, 28.0 ± 1.6 vs. 27.1 ± 1.6 at 150 W, 32.1 ± 3.9 vs. 31.3 ± 3.6 at 200 W, p = 0.03). Blood lactate concentration tended to be higher in HH compared to NH (1.8 ± 0.9 mmol/L vs. 1.7 ± 0.8 mmol/L at 100 W, 3.2 ± 1.8 mmol/L vs. 2.8 ± 1.6 mmol/L at 150 W, 6.0 ± 3.1 mmol/L vs. 5.5 ± 3.0 mmol/L at 200 W, p = 0.08) with a significant interaction effect for exercise intensity (p = 0.02). Conclusions: Cycling during acute exposure to NH appears to result in equivalent cardiorespiratory responses to HH. The more pronounced lactate accumulation in HH should be a topic of future research.

<I>ACTN3</I> R577X Polymorphism Impacts Glucose Consumption at Simulated High Altitude

Introduction: High altitude acclimatization is a process that involve several physiological adjustments, which may increase glucose metabolism because of acute hypoxic exposure. Native highlanders like Tibetans show an increased anaerobic glucose metabolism and a higher proportion of type I muscle fiber than lowlanders. Actin filaments are anchored to the Z line of the sarcomere by a protein called alpha-actinin that exist in two isoforms in the muscle (ACTN2 and ACTN3), however ACTN3 is present only in type II fibers, especially in type IIx. Homozygous individuals for a 577X polymorphism in the ACTN3 gene do not express ACTN3 and seem to be more type I muscle fiber than homozygous individuals 577R. The aim of this study was to compare the glucose consumption response of individuals with different ACTN3 genotypes at simulated 4,500 m altitude. Materials & Methods: Twenty-three volunteers spent four hours exposed to a simulated altitude of 4,500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2 and heart rate were analyzed immediately before entering the chamber and at each hour during the exposure. Results: Glucose after four hours of exposure to hypoxia was different between groups, with RX (68.1 ± 11.7 mg/dl) and RR (71.7 ± 14.4 mg/dl) showing a decreased blood glucose compared to XX (88.7 ± 14.1 mg/dl), indicating an increased dependence on glucose metabolism in individuals with at least one R allele after exposure at 4,500 m simulated altitude. Conclusions: We concluded that individuals with at least one R allele of the ACTN3 R577X gene polymorphism consume more glucose than the ones with XX genotype.

The Farley‐Buneman Spectrum in 2‐D and 3‐D Particle‐in‐Cell Simulations

AbstractSince the 1960s, the Farley‐Buneman instability has played an important role in probing the E‐region ionosphere. The intervening years have seen significant progress in the linear theory of this instability, its relation to other instabilities, and some of its observational signatures. However, the saturation mechanism and nonlinear behavior remain open topics because of their role in controlling energy flow in the E‐region plasma. This paper explores the saturated state of the Farley‐Buneman instability in 2‐D and 3‐D kinetic simulations of the high‐latitude ionosphere, at three different simulated altitudes: 107, 110, and 113 km. These simulations show irregularity amplitude growth and saturation in all runs, but irregularity growth takes much longer in 2‐D than in 3‐D. Once the simulations reach saturation, wave power in the meter‐scale regime falls off as a power law below the wavelength of peak growth, but the power law index is larger in 3‐D than in 2‐D. At longer wavelengths, the 3‐D spectrum is much flatter than the 2‐D spectrum. This implies that purely 2‐D simulations of the Farley‐Buneman instability may overestimate irregularity amplitudes at decameter scales and may also underestimate the efficiency of ion Landau damping at the ion mean‐free‐path scale. From a physical perspective, the relatively flat spectra above the wavelength of peak growth in 3‐D simulations imply a wavelength‐independent saturation mechanism across a range of altitudes. Finally, both 2‐D and 3‐D simulations demonstrate the importance of accounting for zeroth‐order ion drift when estimating the flow angle of density irregularities.

Face Mask Effects of CO2, Heart Rate, Respiration Rate, and Oxygen Saturation on Instructor Pilots

The COVID-19 pandemic has required people to take new measures to mitigate the spread of the communicable virus. Guidelines from health organizations, government offices, and universities have been disseminated. Adherence to these guidelines cannot be more critical for flight training. This study explored the effects face masks had on CO 2 , heart rate, respiration rate, and oxygen saturation while wearing a face mask at an oxygen level simulated to 5,000 feet. Thirty-two instructor pilots (IP) volunteered to participate in the study. IPs spent 90 minutes in a normobaric chamber while wearing a cloth face mask or a paper face mask. Participants were measured before entering the chamber, at the 15-minute mark, at the 45-minute mark, at the 90-minute mark, and after exiting the chamber where they briefly removed their mask for a final measurement. No differences were found between type of face mask. Wearing face masks did not present any potential health or safety issues for the IPs. However, IPs did report moderate dislikes (e.g., comfort, issues with fatigue, restriction of movement) of wearing face masks. Although face masks may be a nuisance, it does not appear to create any health or safety issues at a simulated altitude of 5,000 feet.

Evolution and Preservation of Venous Gas Emboli at Alternating High and Moderate Altitude Exposures.

INTRODUCTION: The evolution and preservation of venous gas emboli (VGE), as markers of decompression stress, were investigated during alternating high- and moderate altitude exposures, thus, simulating a fighter aircraft high-altitude flight, interrupted by refueling excursions to lower altitudes.METHODS: Eight men served as subjects during three normoxic simulated altitude exposures: High = 90 min at 24,000 ft; High-Low = three × 30 min at 24,000 ft, interspersed by two 30-min intervals at 15,000 ft; Low = 90 min at 15,000 ft. VGE scores were assessed by cardiac ultrasound, using a 5-grade scale. Respiratory nitrogen exchange was measured continuously using a modified closed-circuit electronic rebreather.RESULTS: Both High and High-Low induced persistent VGE, with no inter-condition difference either at rest [median (range): High: 1 (0-3), High-Low: 2 (0-3)] or during unloaded knee-bends [High: 3 (1-4), High-Low: 3 (0-4)], whereas VGE was considerably less in Low, both at rest [0 (0-1)] and during knee-bends [0 (0-2)]. In High-Low, VGE decreased temporarily during the 15,000-ft excursions, but resumed pre-excursion values upon return to 24,000 ft. During the final descent to ground level, VGE were more persistent following High-Low than High. In both High and Low, nitrogen was continuously washed out at altitude, whereas in High-Low, the washout at 24,000 ft was interrupted by nitrogen uptake at 15,000 ft.DISCUSSION: In normoxic conditions, long-duration flying at a cabin altitude of 24,000 ft is associated with substantial VGE occurrence, which is not abolished by intermittent excursions to a cabin altitude of 15,000 ft.Ånell R, Grönkvist M, Gennser M, Eiken O. Evolution and preservation of venous gas emboli at alternating high and moderate altitude exposures. Aerosp Med Hum Perform. 2020; 91(1):11-17.

EFFECTS OF VARIOUS HYPOBARIC HYPOXIA ON METABOLIC RESPONSE, SKELETAL MUSCLE OXYGENATION, AND EXERCISE PERFORMANCE IN HEALTHY MALES

Objective This study aimed to evaluate the effect of various levels of hypoxia versus normoxia on exercise perfor-mance, measured by metabolic parameters and skeletal muscle oxygenation profiles during graded exercise test (GXT) in healthy men. Methods In this randomized crossover trial, 11 healthy male participants (age 21.5 ± 2.3 years) performed the GXT using a cycle ergometer at sea-level (760 torr) and at various hypobaric hypoxia: 633, 526, and 433 torr, corresponding to simulated altitudes of 1500, 3000, and 4500 m, respectively. The GXT was started at 50 W and increased by 25 W every 2 min until the participants were exhausted. The pedal frequency was set to 60 rpm. Metabolic parameters (heart rate, HR; minute ventilation, VE; carbon dioxide excretion, VCO2; respiratory exchange ratio, RER; peripheral capillary saturation, SpO2; oxygen consumption, VO2; and blood lactate, O2 pulse) and skeletal muscle oxygen profiles (oxygenated hemoglobin and myoglobin, OxyHb; deoxygenated hemoglobin and myoglobin, DeoxyHb; and tissue oxygen saturation, StO2) were measured for every 2 min during the GXT. Exercise performance was evaluated by maximal oxygen con-sumption, peak power, and duration of exercise time obtained through GXT. Results Regarding metabolic parameters, HR (P < 0.05), VE, (P < 0.05), VCO2 (P < 0.05), RER (P < 0.05), and blood lactate (P < 0.05) showed significant increase under hypoxia compared to normoxia. Moreover, the increase was more pronounced as hypoxia became more severe. However, the SPO2 (P < 0.05) and O2 pulse (P < 0.05) presented a significant decrease under hypoxia compared to normoxia. Similarly, the decrease was more pronounced as hypoxia became more severe. VO2 (P > 0.05) did not show significant difference under different environmental conditions. In skeletal muscle oxygen profiles, none of the param-eters showed noticeable changes. Regarding exercise performance, VO2max (P < 0.05) and exercise time (P < 0.05) decreased significantly as hypoxia became more severe, and peak power (P < 0.05) decreased significantly at simulated altitudes of 3000 and 4500 m compared to normoxia. Conclusion A decrease in exercise performance is due to a decrease in metabolic function under various hypoxia compared to normoxia and the decrease was more pronounced as hypoxia became more severe.

Morphological Characteristic of Melanoma B16 Progression in C57BL/6 Mice with High and Low Resistance to Hypoxia.

The features of B16 melanoma progression in male C57BL/6 mice with initially high and low resistance to hypoxia were studied. To assess the resistance to hypoxia, the mice were placed in a low-pressure chamber at a simulated altitude of 10,000 m. One month after testing, B16 melanoma was inoculated to high- and low-resistant animals. In 19 days after melanoma transplantation, the severity of melanoma progression was assessed by morphological and immunofluorescent methods. The expression of vegf-a and hif-1a in the liver of melanomabearing and control mice was evaluated by real-time PCR. Tumor growth progression was more pronounced in low-resistant mice, which was seen from high weight of the primary tumor node, relative necrosis area, proliferation rates (mitotic index and number of Ki-67+ cells), and expression of vegf-a gene in the liver. In high-resistant to hypoxia animals, the number of caspase-3+ cells dying by apoptosis was higher. The data on more rapid melanoma progression in mice with low resistance to hypoxia should be considered during the search of new prognostic markers and methods for therapy of malignant neoplasms.

Physiological demands of quality cardiopulmonary resuscitation performed at simulated 3250 meters high.

To analyse the effect of oxygen fraction reduction (O2 14%, equivalent to 3250m) on Q-CPR and rescuers' physiological demands. A quasi-experimental study was carried out in a sample of 9 Q-CPR proficient health care professionals. Participants, in teams of 2 people, performed 10min CPR on a Laerdal ResusciAnne mannequin (30:2 compression/ventilation ratio and alternating roles between rescuers every 2min) in two simulated settings: T21-CPR at sea level (FiO2 of 21%) and T14 - CPR at 3250m altitude (FiO2 of 14%). Effort self-perception was rated from 0 (no effort) to 10 (maximum demand) points. Quality of chest compressions was good and similar in both conditions (T21 vs T14). However, the percentage of ventilations with adequate tidal volume was lower in altitude than at sea level conditions (35.9±25.2% vs. 54.7±23.2%, p=0.035). The subjective perception of effort was significantly higher at simulated altitude (5±2) than at sea level (3±2) (p=0.038). Maximum heart rate during the tests was similar in both conditions; however, mean oxygen saturation was significantly lower in altitude conditions (90.5±2.5% vs. 99.3±0.5%, p<0.001). Although performing CPR under simulated hypoxic altitude conditions significantly increases the physiological demands and subjective feeling of tiredness compared to sea level CPR, trained rescuers are able to deliver good Q-CPR in such conditions, at least in the first 10min of resuscitation.

Higher Muscle Tissue Oxygenation When Exposed to Hypobaric Hypoxia Than Normobaric Hypoxia

There has been recent debate on the potential difference in physiological response between exposure to simulated altitude (normobaric hypoxia) and terrestrial altitude (hypobaric hypoxia). Purpose: To determine the difference in the physiological response to normobaric and hypobaric hypoxia during exercise. Methods: Eight recreationally active subjects (27 ± 5 y old, 73.1 ± 7.4 kg body weight, 170.6 ± 6.7 cm height, and 19.3 ± 9.2 % body fat) completed incremental cycling exercise to volitional fatigue in three separate environments: normobaric normoxia (NN; 350 m), normobaric hypoxia (NH; simulated 3094 m), and hypobaric hypoxia (HH; 3094 m). Heart rate, blood oxygen saturation, and muscle tissue oxygenation were measured at rest and continuously throughout the exercise trials. Results: Blood oxygen saturation (SpO2) was ~10% higher in NN compared to the two hypoxic conditions (p < 0.001) at rest and all exercise stages, with no difference between NH and HH (p > 0.05). Heart rate was higher at rest in HH (98 ± 13 bpm) compared to NN (83 ± 15 bpm, p = 0.011) and NH (84 ± 14 bpm, p = 0.001) which persisted until 165 watts at which point no difference was observed (p > 0.05). Muscle tissue oxygenation was 17% higher in HH compared to NN and 19% higher than NH throughout exposure (p < 0.05). Conclusion: This data indicates that the hypoxic stress resulting from normobaric and hypobaric hypoxia are not the sameand that hypobaric hypoxia may not result in hypoxia at the level of the tissue.

Acetazolamide does not alter endurance exercise performance at 3,500-m altitude.

Acetazolamide (AZ) is a medication commonly used to prevent acute mountain sickness (AMS) during rapid ascent to high altitude. However, it is unclear whether AZ use impairs exercise performance; previous literature regarding this topic is equivocal. The purpose of this study was to evaluate the impact of AZ on time-trial (TT) performance during a 30-h exposure to hypobaric hypoxia equivalent to 3,500-m altitude. Ten men [sea-level peak oxygen consumption (VO2peak): 50.8 ± 6.5 mL·kg-1·min-1; body fat %: 20.6 ± 5.2%] completed 2 30-h exposures at 3,500 m. In a crossover study design, subjects were given 500 mg/day of either AZ or a placebo. Exercise testing was completed 2 h and 24 h after ascent and consisted of 15-min steady-state treadmill walking at 40%-45% sea-level VO2peak, followed by a 2-mile self-paced treadmill TT. AMS was assessed after ~12 h and 22 h at 3,500 m. The incidence of AMS decreased from 40% with placebo to 0% with AZ. Oxygen saturation was higher (P < 0.05) in AZ versus placebo trials at the end of the TT after 2 h (85 ± 3% vs. 79 ± 3%) and 24 h (86 ± 3% vs. 81 ± 4%). There was no difference in time to complete 2 miles between AZ and PL after 2 h (20.7 ± 3.2 vs. 22.7 ± 5.0 min, P > 0.05) or 24 h (21.5 ± 3.4 vs. 21.1 ± 2.9 min, P > 0.05) of exposure to altitude. Our results suggest that AZ (500 mg/day) does not negatively impact endurance exercise performance at 3,500 m.NEW & NOTEWORTHY To our knowledge, this is the first study to examine the impact of acetazolamide (500 mg/day) versus placebo on self-paced, peak-effort exercise performance using a short-duration exercise test in a hypobaric hypoxic environment with a repeated-measures design. In the present study, acetazolamide did not impact exercise performance after 2-h or 24-h exposure to 3,500-m simulated altitude.

Association between ACTN3 and acute mountain sickness

BackgroundDuring the process of acclimatization, when our organism needs to adjust several metabolic processes in the attempt of establishing a better oxygenation, it is normal that individuals present some symptoms that can lead to the disease of the mountain. However, not everyone presents such symptoms and individuals native of high altitudes regions present genetic differences compared to natives of low altitudes which can generate a better acute adaptation. One of these differences is the higher proportion of type I muscle fibers, which may originate from the R577X polymorphism of the ACTN3 gene. The aim of this study was to compare the response of individuals with different ACTN3 genotypes at simulated 4500 m altitude on the presence of Acute Mountain Sickness (AMS) symptoms. Twenty-three volunteers (RR = 7, RX = 8, XX = 8) spent 4 hours exposed to a simulated altitude of 4500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2, heart rate and the symptoms of AMS were analyzed immediately before entering the chamber and at each hour of exposure. Statistical analysis was performed using IBM SPSS Statistics 21 software.ResultsOur results point to an association between AMS symptoms and the presence of R allele from R577X polymorphism.ConclusionWe conclude that individuals with at least one R allele of the R577X polymorphism seems to be more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms.

Platelet Hyperreactivity in Advanced Age is Governed by the Novel Adaptive Changes in Intraplatelet Antioxidants

While endoplasmic reticulum (ER) stress has been observed in several human diseases, few studies have reported the involvement of ER stress in chronic hypoxia (CH) induced cardiac damage. Hypoxia, such as that prevalent at high altitude (HA), forms the underlying cause of several maladies including cardiovascular diseases. While the role of hypoxia inducible factor-1 (HIF-1α) in the adaptive responses to hypoxia is known, the role of the unfolded protein response (UPR) is only recently being explored in the HA pathophysiologies. The present study investigates the effect of ER stress modulation on CH mediated injury and the cardioprotective action of 4-phenylbutyric acid (PBA) in enhancing survival response under hypoxia. Here, we observed that exposure of rats, for 1, 7 and 14 days CH to a simulated altitude of 7620 m, led to cardiac hypertrophy and significant protein oxidation. This induced the activation of UPR signaling mechanisms, mediated by PERK, IRE1α and ATF6. By 14 days, there was a marked upregulation of apoptosis, evident in increased CHOP and caspase-3/9 activity. PBA reduced CH induced right ventricular enlargement and apoptosis. Further, in contrast to tunicamycin, PBA considerably enhanced hypoxic tolerance. An elevation in the level of antioxidant enzymes, HIF-1α and its regulated proteins (HO-1, GLUT-1) was observed in the PBA administered animals, along with a concomitant suppression of UPR markers. Our study thus emphasizes upon the attenuation of ER stress by PBA as a mechanism to diminish CH induced cardiac injury and boost hypoxic survival, providing an insight into the novel relationship between the HIF-1α and UPR under hypoxia.