Sample records for high altitude hypoxia

  1. Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates.

    PubMed

    Storz, Jay F; Scott, Graham R; Cheviron, Zachary A

    2010-12-15

    High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

  2. Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

    PubMed Central

    Storz, Jay F.; Scott, Graham R.; Cheviron, Zachary A.

    2010-01-01

    High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change. PMID:21112992

  3. AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

    PubMed Central

    D’Alessandro, Angelo; Nemkov, Travis; Sun, Kaiqi; Liu, Hong; Song, Anren; Monte, Andrew A.; Subudhi, Andrew W.; Lovering, Andrew T.; Dvorkin, Daniel; Julian, Colleen G.; Kevil, Christopher G.; Kolluru, Gopi K.; Shiva, Sruthi; Gladwin, Mark T.; Xia, Yang; Hansen, Kirk C.; Roach, Robert C.

    2017-01-01

    Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory. PMID:27646145

  4. Thoracic skeletal morphology and high-altitude hypoxia in Andean prehistory.

    PubMed

    Weinstein, Karen J

    2007-09-01

    Living humans from the highland Andes exhibit antero-posteriorly and medio-laterally enlarged chests in response to high-altitude hypoxia. This study hypothesizes that morphological responses to high-altitude hypoxia should also be evident in pre-Contact Andean groups. Thoracic skeletal morphology in four groups of human skeletons (N = 347) are compared: two groups from coastal regions (Ancón, Peru, n = 79 and Arica, Chile, n = 123) and two groups from high altitudes (San Pedro de Atacama, Chile, n = 102 and Machu Picchu and Cuzco, Peru, n = 43). Osteometric variables that represent proportions of chest width and depth include sternal and clavicular lengths and breadths and rib length, curvature, and area. Each variable was measured relative to body size, transformed into logarithmic indices, and compared across sex-specific groups using ANOVA and Tukey multiple comparison tests. Atacama highlanders have the largest sternal and clavicular proportions and ribs with the greatest area and least amount of curvature, features that suggest an antero-posteriorly deep and mediolaterally wide thoracic skeleton. Ancón lowlanders exhibit proportions indicating narrower and shallower chests. Machu Picchu and Cuzco males cluster with the other highland group in rib curvature and area at the superior levels of the thorax, whereas chest proportions in Machu Picchu and Cuzco females resemble those of lowlanders. The variation in Machu Picchu and Cuzco males and females is interpreted as the result of population migrations. The presence of morphological traits indicative of enlarged chests in some highland individuals suggests that high-altitude hypoxia was an environmental stressor shaping the biology of highland Andean groups during the pre-Contact period. (c) 2007 Wiley-Liss, Inc.

  5. [Effect of high altitude hypoxia on the human EEG].

    PubMed

    Daniiarov, S B; Vilenskaia, E M

    1980-01-01

    The paper presents the results of the comparative study of the EEG at alpine altitudes (Tuya -- Ashu pass, 3200 m) and at low altitudes (City of Frunze, 760 m above the sea level). The dynamics of EEG changes at different stages of adaptation to hypoxia is also traced. The obtained data show that the alpine hypoxia produces a considerable intensification of the excitation processes in the cerebral cortex. Different sensitivity to the oxigen shortage has been found in the frontal-temporal parts of the right and the left hemispheres.

  6. Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics.

    PubMed

    Chicco, Adam J; Le, Catherine H; Gnaiger, Erich; Dreyer, Hans C; Muyskens, Jonathan B; D'Alessandro, Angelo; Nemkov, Travis; Hocker, Austin D; Prenni, Jessica E; Wolfe, Lisa M; Sindt, Nathan M; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

    2018-05-04

    Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia down-regulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose toward pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity in vivo Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Icenogle, M.; Scotto, P.; Robergs, R.; Hinghofer-Szalkay, H.; Roach, R. C.; Leoppky, J. A. (Principal Investigator)

    1997-01-01

    To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

  8. Cerebral blood flow and oxygenation in ovine fetus: responses to superimposed hypoxia at both low and high altitude

    PubMed Central

    Peňa, Jorge Pereyra; Tomimatsu, Takuji; Hatran, Douglas P; McGill, Lisa L; Longo, Lawrence D

    2007-01-01

    For the fetus, although the roles of arterial blood gases are recognized to be critical in the regulation of cerebral blood flow (CBF) and cerebral oxygenation, the relation of CBF, cortical tissue PO2 (t PO2), sagittal sinus PO2, and related indices of cerebral oxygenation to arterial blood gases are not well defined. This is particularly true for that fetus subjected to long-term hypoxia (LTH). In an effort to elucidate these interrelations, we tested the hypothesis that in the fetus acclimatized to high altitude, cerebral oxygenation is not compromised relative to that at low altitude. By use of a laser Doppler flowmeter with a fluorescent O2 probe, in near-term fetal sheep at low altitude (n = 8) and those acclimatized to high altitude hypoxia (3801 m for 90 ± 5 days; n = 6), we measured laser Doppler CBF (LD-CBF), t PO2, and related variables in response to 40 min superimposed hypoxia. At both altitudes, fetal LD-CBF, cerebral O2 delivery, t PO2, and several other variables including sagittal sinus PO2, correlated highly with arterial PO2 (Pa,O2). In response to superimposed hypoxia (Pa,O2 = 11 ± 1 Torr), LD-CBF was significantly blunted at high altitude, as compared with that at low altitude. In the two altitude groups fetal cerebral oxygenation was similar under both control conditions and with superimposed hypoxia, cortical t PO2 decreasing from 8 ± 1 and 6 ± 1 Torr, respectively, to 2 ± 1 Torr. Also, for these conditions sagittal sinus PO2 and [HbO2] values were similar. In response to superimposed hypoxia, cerebral metabolic rate for O2 decreased ∼50% in each group (P < 0.05). For both the fetus at low altitude and that acclimatized to high altitude LTH, we present the first dose–response data on the relation of LD-CBF, cortical t PO2, and sagittal sinus blood gas values to Pa,O2. In addition, despite differences in several variables, the fetus at high altitude showed evidence of successful acclimatization, supporting the hypothesis that such

  9. Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress

    PubMed Central

    2013-01-01

    Background At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function. Methods The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression. Results The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression. Conclusions Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude

  10. Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress.

    PubMed

    Parraguez, Víctor H; Urquieta, Bessie; Pérez, Laura; Castellaro, Giorgio; De los Reyes, Mónica; Torres-Rovira, Laura; Aguado-Martínez, Adriana; Astiz, Susana; González-Bulnes, Antonio

    2013-03-23

    At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function. The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression. The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression. Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude.

  11. Acclimation to hypoxia increases carbohydrate use during exercise in high-altitude deer mice

    PubMed Central

    Lau, Daphne S.; Connaty, Alex D.; Mahalingam, Sajeni; Wall, Nastashya; Cheviron, Zachary A.; Storz, Jay F.; Scott, Graham R.

    2017-01-01

    The low O2 experienced at high altitude is a significant challenge to effective aerobic locomotion, as it requires sustained tissue O2 delivery in addition to the appropriate allocation of metabolic substrates. Here, we tested whether high- and low-altitude deer mice (Peromyscus maniculatus) have evolved different acclimation responses to hypoxia with respect to muscle metabolism and fuel use during submaximal exercise. Using F1 generation high- and low-altitude deer mice that were born and raised in common conditions, we assessed 1) fuel use during exercise, 2) metabolic enzyme activities, and 3) gene expression for key transporters and enzymes in the gastrocnemius. After hypoxia acclimation, highland mice showed a significant increase in carbohydrate oxidation and higher relative reliance on this fuel during exercise at 75% maximal O2 consumption. Compared with lowland mice, highland mice had consistently higher activities of oxidative and fatty acid oxidation enzymes in the gastrocnemius. In contrast, only after hypoxia acclimation did activities of hexokinase increase significantly in the muscle of highland mice to levels greater than lowland mice. Highland mice also responded to acclimation with increases in muscle gene expression for hexokinase 1 and 2 genes, whereas both populations increased mRNA expression for glucose transporters. Changes in skeletal muscle with acclimation suggest that highland mice had an increased capacity for the uptake and oxidation of circulatory glucose. Our results demonstrate that highland mice have evolved a distinct mode of hypoxia acclimation that involves an increase in carbohydrate use during exercise. PMID:28077391

  12. Altitude matters: differences in cardiovascular and respiratory responses to hypoxia in bar-headed geese reared at high and low altitudes.

    PubMed

    Lague, Sabine L; Chua, Beverly; Farrell, Anthony P; Wang, Yuxiang; Milsom, William K

    2016-07-01

    Bar-headed geese (Anser indicus) fly at high altitudes during their migration across the Himalayas and Tibetan plateau. However, we know relatively little about whether rearing at high altitude (i.e. phenotypic plasticity) facilitates this impressive feat because most of what is known about their physiology comes from studies performed at sea level. To provide this information, a comprehensive analysis of metabolic, cardiovascular and ventilatory responses to progressive decreases in the equivalent fractional composition of inspired oxygen (FiO2 : 0.21, 0.12, 0.09, 0.07 and 0.05) was made on bar-headed geese reared at either high altitude (3200 m) or low altitude (0 m) and on barnacle geese (Branta leucopsis), a low-altitude migrating species, reared at low altitude (0 m). Bar-headed geese reared at high altitude exhibited lower metabolic rates and a modestly increased hypoxic ventilatory response compared with low-altitude-reared bar-headed geese. Although the in vivo oxygen equilibrium curves and blood-oxygen carrying capacity did not differ between the two bar-headed goose study groups, the blood-oxygen carrying capacity was higher than that of barnacle geese. Resting cardiac output also did not differ between groups and increased at least twofold during progressive hypoxia, initially as a result of increases in stroke volume. However, cardiac output increased at a higher FiO2  threshold in bar-headed geese raised at high altitude. Thus, bar-headed geese reared at high altitude exhibited a reduced oxygen demand at rest and a modest but significant increase in oxygen uptake and delivery during progressive hypoxia compared with bar-headed geese reared at low altitude. © 2016. Published by The Company of Biologists Ltd.

  13. High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

    PubMed

    Vavricka, Stephan R; Rogler, Gerhard; Biedermann, Luc

    2016-01-01

    The importance of environmental factors in the pathogenesis including their disease-modifying potential are increasingly recognized in inflammatory bowel disease (IBD) patients, largely driven by the perception that the prevalence and incidence of IBD are on the rise within the last few years, especially in non-western countries. One of those factors is believed to be hypoxia. The role of hypoxia as a modifying or even causative factor in the genesis and maintenance of inflammation has been increasingly elucidated in recent years. Hypoxia is believed to be a main inducing factor of inflammation. This has been studied in different animal experiments as well as in humans exposed to hypoxia. In several studies - mainly in mice - animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future. © 2016 S. Karger AG, Basel.

  14. Shared Genetic Signals of Hypoxia Adaptation in Drosophila and in High-Altitude Human Populations

    PubMed Central

    Jha, Aashish R.; Zhou, Dan; Brown, Christopher D.; Kreitman, Martin; Haddad, Gabriel G.; White, Kevin P.

    2016-01-01

    The ability to withstand low oxygen (hypoxia tolerance) is a polygenic and mechanistically conserved trait that has important implications for both human health and evolution. However, little is known about the diversity of genetic mechanisms involved in hypoxia adaptation in evolving populations. We used experimental evolution and whole-genome sequencing in Drosophila melanogaster to investigate the role of natural variation in adaptation to hypoxia. Using a generalized linear mixed model we identified significant allele frequency differences between three independently evolved hypoxia-tolerant populations and normoxic control populations for approximately 3,800 single nucleotide polymorphisms. Around 50% of these variants are clustered in 66 distinct genomic regions. These regions contain genes that are differentially expressed between hypoxia-tolerant and normoxic populations and several of the differentially expressed genes are associated with metabolic processes. Additional genes associated with respiratory and open tracheal system development also show evidence of directional selection. RNAi-mediated knockdown of several candidate genes’ expression significantly enhanced survival in severe hypoxia. Using genomewide single nucleotide polymorphism data from four high-altitude human populations—Sherpas, Tibetans, Ethiopians, and Andeans, we found that several human orthologs of the genes under selection in flies are also likely under positive selection in all four high-altitude human populations. Thus, our results indicate that selection for hypoxia tolerance can act on standing genetic variation in similar genes and pathways present in organisms diverged by hundreds of millions of years. PMID:26576852

  15. High altitude illness

    PubMed

    Hartman-Ksycińska, Anna; Kluz-Zawadzka, Jolanta; Lewandowski, Bogumił

    High-altitude illness is a result of prolonged high-altitude exposure of unacclimatized individuals. The illness is seen in the form of acute mountain sickness (AMS) which if not treated leads to potentially life-threatening high altitude pulmonary oedema and high-altitude cerebral oedema. Medical problems are caused by hypobaric hypoxia stimulating hypoxia-inducible factor (HIF) release. As a result, the central nervous system, circulation and respiratory system function impairment occurs. The most important factor in AMS treatment is acclimatization, withdrawing further ascent and rest or beginning to descent; oxygen supplementation, and pharmacological intervention, and, if available, a portable hyperbaric chamber. Because of the popularity of high-mountain sports and tourism better education of the population at risk is essential.

  16. Brain Food at High Altitude.

    PubMed

    Jain, Vishal

    2016-01-01

    Scenic view at high altitude is a pleasure to the eyes, but it has some shortcoming effects as well. High altitude can be divided into different categories, i.e., high altitude (3000-5000 ft), very high altitude (5000-8000 ft), and extreme altitude (above 8000 ft). Much of the population resides at high altitude, and others go there for tourism. Military personnel are also posted there to defend boundaries. As we ascent to high altitude, partial pressure of oxygen reduces, whereas concentration remains the same; this reduces the availability of oxygen to different body parts. This pathophysiological condition is known as hypobaric hypoxia (HH) which leads to oxidative stress and further causes cognitive dysfunction in some cases. Hypoxia causes neurodegeneration in different brain regions; however, the hippocampus is found to be more prone in comparison to other brain regions. As the hippocampus is affected most, therefore, spatial memory is impaired most during such condition. This chapter will give a brief review of the damaging effect of high altitude on cognition and also throw light on possible herbal interventions at high altitude, which can improve cognitive performance as well as provide protection against the deteriorating effect of hypobaric hypoxia at high altitude.

  17. Acute hypoxia in a simulated high-altitude airdrop scenario due to oxygen system failure.

    PubMed

    Ottestad, William; Hansen, Tor Are; Pradhan, Gaurav; Stepanek, Jan; Høiseth, Lars Øivind; Kåsin, Jan Ivar

    2017-12-01

    High-Altitude High Opening (HAHO) is a military operational procedure in which parachute jumps are performed at high altitude requiring supplemental oxygen, putting personnel at risk of acute hypoxia in the event of oxygen equipment failure. This study was initiated by the Norwegian Army to evaluate potential outcomes during failure of oxygen supply, and to explore physiology during acute severe hypobaric hypoxia. A simulated HAHO without supplemental oxygen was carried out in a hypobaric chamber with decompression to 30,000 ft (9,144 m) and then recompression to ground level with a descent rate of 1,000 ft/min (305 m/min). Nine subjects were studied. Repeated arterial blood gas samples were drawn throughout the entire hypoxic exposure. Additionally, pulse oximetry, cerebral oximetry, and hemodynamic variables were monitored. Desaturation evolved rapidly and the arterial oxygen tensions are among the lowest ever reported in volunteers during acute hypoxia. Pa O 2 decreased from baseline 18.4 (17.3-19.1) kPa, 138.0 (133.5-143.3) mmHg, to a minimum value of 3.3 (2.9-3.7) kPa, 24.8 (21.6-27.8) mmHg, after 180 (60-210) s, [median (range)], N = 9. Hyperventilation with ensuing hypocapnia was associated with both increased arterial oxygen saturation and cerebral oximetry values, and potentially improved tolerance to severe hypoxia. One subject had a sharp drop in heart rate and cardiac index and lost consciousness 4 min into the hypoxic exposure. A simulated high-altitude airdrop scenario without supplemental oxygen results in extreme hypoxemia and may result in loss of consciousness in some individuals. NEW & NOTEWORTHY This is the first study to investigate physiology and clinical outcome of oxygen system failure in a simulated HAHO scenario. The acquired knowledge is of great value to make valid risk-benefit analyses during HAHO training or operations. The arterial oxygen tensions reported in this hypobaric chamber study are among the lowest ever reported during acute

  18. Beneficial Role of Erythrocyte Adenosine A2B Receptor-Mediated AMP-Activated Protein Kinase Activation in High-Altitude Hypoxia.

    PubMed

    Liu, Hong; Zhang, Yujin; Wu, Hongyu; D'Alessandro, Angelo; Yegutkin, Gennady G; Song, Anren; Sun, Kaiqi; Li, Jessica; Cheng, Ning-Yuan; Huang, Aji; Edward Wen, Yuan; Weng, Ting Ting; Luo, Fayong; Nemkov, Travis; Sun, Hong; Kellems, Rodney E; Karmouty-Quintana, Harry; Hansen, Kirk C; Zhao, Bihong; Subudhi, Andrew W; Jameson-Van Houten, Sonja; Julian, Colleen G; Lovering, Andrew T; Eltzschig, Holger K; Blackburn, Michael R; Roach, Robert C; Xia, Yang

    2016-08-02

    High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust to hypoxia may lead to pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation to high altitude may reveal novel therapeutics to counteract the detrimental consequences of hypoxia. Using high-throughput, unbiased metabolomic profiling, we report that the metabolic pathway responsible for production of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric regulator of hemoglobin-O2 binding affinity, was significantly induced in 21 healthy humans within 2 hours of arrival at 5260 m and further increased after 16 days at 5260 m. This finding led us to discover that plasma adenosine concentrations and soluble CD73 activity rapidly increased at high altitude and were associated with elevated erythrocyte 2,3-BPG levels and O2 releasing capacity. Mouse genetic studies demonstrated that elevated CD73 contributed to hypoxia-induced adenosine accumulation and that elevated adenosine-mediated erythrocyte A2B adenosine receptor activation was beneficial by inducing 2,3-BPG production and triggering O2 release to prevent multiple tissue hypoxia, inflammation, and pulmonary vascular leakage. Mechanistically, we demonstrated that erythrocyte AMP-activated protein kinase was activated in humans at high altitude and that AMP-activated protein kinase is a key protein functioning downstream of the A2B adenosine receptor, phosphorylating and activating BPG mutase and thus inducing 2,3-BPG production and O2 release from erythrocytes. Significantly, preclinical studies demonstrated that activation of AMP-activated protein kinase enhanced BPG mutase activation, 2,3-BPG production, and O2 release capacity in CD73-deficient mice, in erythrocyte-specific A2B adenosine receptor knockouts, and in wild-type mice and in turn reduced tissue hypoxia and inflammation. Together, human and mouse studies reveal novel

  19. High-altitude ancestry and hypoxia acclimation have distinct effects on exercise capacity and muscle phenotype in deer mice

    PubMed Central

    Lui, Mikaela A.; Mahalingam, Sajeni; Patel, Paras; Connaty, Alex D.; Ivy, Catherine M.; Cheviron, Zachary A.; Storz, Jay F.; McClelland, Grant B.

    2015-01-01

    The hypoxic and cold environment at high altitudes requires that small mammals sustain high rates of O2 transport for exercise and thermogenesis while facing a diminished O2 availability. We used laboratory-born and -raised deer mice (Peromyscus maniculatus) from highland and lowland populations to determine the interactive effects of ancestry and hypoxia acclimation on exercise performance. Maximal O2 consumption (V̇o2max) during exercise in hypoxia increased after hypoxia acclimation (equivalent to the hypoxia at ∼4,300 m elevation for 6–8 wk) and was consistently greater in highlanders than in lowlanders. V̇o2max during exercise in normoxia was not affected by ancestry or acclimation. Highlanders also had consistently greater capillarity, oxidative fiber density, and maximal activities of oxidative enzymes (cytochrome c oxidase and citrate synthase) in the gastrocnemius muscle, lower lactate dehydrogenase activity in the gastrocnemius, and greater cytochrome c oxidase activity in the diaphragm. Hypoxia acclimation did not affect any of these muscle traits. The unique gastrocnemius phenotype of highlanders was associated with higher mRNA and protein abundances of peroxisome proliferator-activated receptor γ (PPARγ). Vascular endothelial growth factor (VEGFA) transcript abundance was lower in highlanders, and hypoxia acclimation reduced the expression of numerous genes that regulate angiogenesis and energy metabolism, in contrast to the observed population differences in muscle phenotype. Lowlanders exhibited greater increases in blood hemoglobin content, hematocrit, and wet lung mass (but not dry lung mass) than highlanders after hypoxia acclimation. Genotypic adaptation to high altitude, therefore, improves exercise performance in hypoxia by mechanisms that are at least partially distinct from those underlying hypoxia acclimation. PMID:25695288

  20. Effect of acute exposure to moderate altitude on muscle power: hypobaric hypoxia vs. normobaric hypoxia.

    PubMed

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch-Góngora, Juan G; Galilea, Pedro A; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest P(mean) obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to P(max) (∼ 3%) and maximal strength (1 RM) (∼ 6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on P(mean) and P(peak) in the middle-high part of the curve (≥ 60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1 RM, movement velocity and power during the execution of a force-velocity curve in bench press.

  1. Effect of Acute Exposure to Moderate Altitude on Muscle Power: Hypobaric Hypoxia vs. Normobaric Hypoxia

    PubMed Central

    Feriche, Belén; García-Ramos, Amador; Calderón-Soto, Carmen; Drobnic, Franchek; Bonitch- Góngora, Juan G.; Galilea, Pedro A.; Riera, Joan; Padial, Paulino

    2014-01-01

    When ascending to a higher altitude, changes in air density and oxygen levels affect the way in which explosive actions are executed. This study was designed to compare the effects of acute exposure to real or simulated moderate hypoxia on the dynamics of the force-velocity relationship observed in bench press exercise. Twenty-eight combat sports athletes were assigned to two groups and assessed on two separate occasions: G1 (n = 17) in conditions of normoxia (N1) and hypobaric hypoxia (HH) and G2 (n = 11) in conditions of normoxia (N2) and normobaric hypoxia (NH). Individual and complete force-velocity relationships in bench press were determined on each assessment day. For each exercise repetition, we obtained the mean and peak velocity and power shown by the athletes. Maximum power (Pmax) was recorded as the highest Pmean obtained across the complete force-velocity curve. Our findings indicate a significantly higher absolute load linked to Pmax (∼3%) and maximal strength (1RM) (∼6%) in G1 attributable to the climb to altitude (P<0.05). We also observed a stimulating effect of natural hypoxia on Pmean and Ppeak in the middle-high part of the curve (≥60 kg; P<0.01) and a 7.8% mean increase in barbell displacement velocity (P<0.001). No changes in any of the variables examined were observed in G2. According to these data, we can state that acute exposure to natural moderate altitude as opposed to simulated normobaric hypoxia leads to gains in 1RM, movement velocity and power during the execution of a force-velocity curve in bench press. PMID:25474104

  2. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

    PubMed

    Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

    2002-04-01

    Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

  3. The protein level of hypoxia-inducible factor-1alpha is increased in the plateau pika (Ochotona curzoniae) inhabiting high altitudes.

    PubMed

    Li, Hong-Ge; Ren, Yong-Ming; Guo, Song-Chang; Cheng, Long; Wang, De-Peng; Yang, Jie; Chang, Zhi-Jie; Zhao, Xin-Quan

    2009-02-01

    The plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant species living only at 3,000-5,000 m above sea-level on the Qinghai-Tibetan plateau. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates a variety of cellular and systemic adaptations to hypoxia. To investigate how the plateau pika adapts to a high-altitude hypoxic environment at the molecular level, we examined the expression pattern of the HIF-1alpha protein in the pika by Western blot and immunohistochemical analysis. We found that HIF-1alpha protein is expressed at a significantly high level in the pika, which is higher in most tissues (particularly in the lung, liver, spleen and kidney) of the plateau pika than that of mice living at sea-level. Importantly, we found that the protein levels of HIF-1alpha in the lung, liver, spleen and kidney of the pika were increased with increased habitat altitudes. We observed that the plateau pika HIF-1alpha localized to the nucleus of cells by an immunostaining analysis, and enhanced HRE-driven gene expression by luciferase reporter assays. Our study suggests that the HIF-1alpha protein levels are related to the adaptation of the plateau pika to the high-altitude hypoxic environment.

  4. Altitude-related hypoxia: risk assessment and management for passengers on commerical aircraft.

    PubMed

    Mortazavi, Amir; Eisenberg, Mark J; Langleben, David; Ernst, Pierre; Schiff, Renee L

    2003-09-01

    Individuals with pulmonary and cardiac disorders are particularly at risk of developing hypoxemia at altitude. Our objective is to describe the normal and maladaptive physiological responses to altitude-related hypoxia, to review existing methods and guidelines for preflight assessment of air travelers, and to provide recommendations for treatment of hypoxia at altitude. Falling partial pressure of oxygen with altitude results in a number of physiologic adaptations including hyperventilation, pulmonary vasoconstriction, altered ventilation/perfusion matching, and increased sympathetic tone. According to three guideline statements, the arterial pressure of oxygen (PaO2) should be maintained above 50 to 55 mm Hg at all altitudes. General indicators such as oxygen saturation and sea level blood gases may be useful in predicting altitude hypoxia. More specialized techniques for estimation of altitude PaO2, such as regression equations, hypoxia challenge testing, and hypobaric chamber exposure have also been examined. A regression equation using sea level PaO2 and spirometric parameters can be used to estimate PaO2 at altitude. Hypoxia challenge testing, performed by exposing subjects to lower inspired FIO2 at sea level may be more precise. Hypobaric chamber exposure, the gold standard, mimics lower barometric pressure, but is mainly used in research. Oxygen supplementation during air travel is needed for individuals with an estimated PaO2 (8000 ft) below 50 mmHg. There are a number of guidelines for the pre-flight assessment of patients with pulmonary and/or cardiac diseases. However, these data are based on small studies in patients with a limited group of diseases.

  5. Dark Adaptation at High Altitude: An Unexpected Pupillary Response to Chronic Hypoxia in Andean Highlanders.

    PubMed

    Healy, Katherine; Labrique, Alain B; Miranda, J Jaime; Gilman, Robert H; Danz, David; Davila-Roman, Victor G; Huicho, Luis; León-Velarde, Fabiola; Checkley, William

    2016-09-01

    Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO 2 ) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m 2 ) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO 2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO 2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO 2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This

  6. Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds.

    PubMed

    Scott, Graham R; Cadena, Viviana; Tattersall, Glenn J; Milsom, William K

    2008-04-01

    The objectives of this study were to compare the thermoregulatory, metabolic and ventilatory responses to hypoxia of the high altitude bar-headed goose with low altitude waterfowl. All birds were found to reduce body temperature (T(b)) during hypoxia, by up to 1-1.5 degrees C in severe hypoxia. During prolonged hypoxia, T(b) stabilized at a new lower temperature. A regulated increase in heat loss contributed to T(b) depression as reflected by increases in bill surface temperatures (up to 5 degrees C) during hypoxia. Bill warming required peripheral chemoreceptor inputs, since vagotomy abolished this response to hypoxia. T(b) depression could still occur without bill warming, however, because vagotomized birds reduced T(b) as much as intact birds. Compared to both greylag geese and pekin ducks, bar-headed geese required more severe hypoxia to initiate T(b) depression and heat loss from the bill. However, when T(b) depression or bill warming were expressed relative to arterial O(2) concentration (rather than inspired O(2)) all species were similar; this suggests that enhanced O(2) loading, rather than differences in thermoregulatory control centres, reduces T(b) depression during hypoxia in bar-headed geese. Correspondingly, bar-headed geese maintained higher rates of metabolism during severe hypoxia (7% inspired O(2)), but this was only partly due to differences in T(b). Time domains of the hypoxic ventilatory response also appeared to differ between bar-headed geese and low altitude species. Overall, our results suggest that birds can adjust peripheral heat dissipation to facilitate T(b) depression during hypoxia, and that bar-headed geese minimize T(b) and metabolic depression as a result of evolutionary adaptations that enhance O(2) transport.

  7. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia

    PubMed Central

    Sun, Kaiqi; Zhang, Yujin; D'Alessandro, Angelo; Nemkov, Travis; Song, Anren; Wu, Hongyu; Liu, Hong; Adebiyi, Morayo; Huang, Aji; Wen, Yuan E.; Bogdanov, Mikhail V.; Vila, Alejandro; O'Brien, John; Kellems, Rodney E.; Dowhan, William; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Safo, Martin; Hansen, Kirk C.; Roach, Robert C.; Xia, Yang

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity. Mouse genetic studies show that elevated erythrocyte Sphk1-induced S1P protects against tissue hypoxia by inducing O2 release. Mechanistically, we show that intracellular S1P promotes deoxygenated Hb anchoring to the membrane, enhances the release of membrane-bound glycolytic enzymes to the cytosol, induces glycolysis and thus the production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific glycolytic intermediate, which facilitates O2 release. Altogether, we reveal S1P as an intracellular hypoxia-responsive biolipid promoting erythrocyte glycolysis, O2 delivery and thus new therapeutic opportunities to counteract tissue hypoxia. PMID:27417539

  8. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

    PubMed

    Gonzales, Gustavo F

    2011-03-01

    The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

  9. Can High Altitude Influence Cytokines and Sleep?

    PubMed Central

    de Aquino Lemos, Valdir; dos Santos, Ronaldo Vagner Thomatieli; Lira, Fabio Santos; Rodrigues, Bruno; Tufik, Sergio; de Mello, Marco Tulio

    2013-01-01

    The number of persons who relocate to regions of high altitude for work, pleasure, sport, or residence increases every year. It is known that the reduced supply of oxygen (O2) induced by acute or chronic increases in altitude stimulates the body to adapt to new metabolic challenges imposed by hypoxia. Sleep can suffer partial fragmentation because of the exposure to high altitudes, and these changes have been described as one of the responsible factors for the many consequences at high altitudes. We conducted a review of the literature during the period from 1987 to 2012. This work explored the relationships among inflammation, hypoxia and sleep in the period of adaptation and examined a novel mechanism that might explain the harmful effects of altitude on sleep, involving increased Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) production from several tissues and cells, such as leukocytes and cells from skeletal muscle and brain. PMID:23690660

  10. Effect of chronic altitude hypoxia on hematologic and glycolytic parameters.

    PubMed

    Clench, J; Ferrell, R E; Schull, W J

    1982-05-01

    The physiological effect of chronic exposure to altitude hypoxia on the glycolytic intermediates, adenosine triphosphate and 2,3-diphosphoglyceric acid, and the hematologic parameters, hemoglobin, hematocrit, and mean cell hemoglobin concentration, has been examined in an indigenous population, the Aymara, of the Departamento de Arica, Chile. This population normally resides at three altitudes: the coast (0-500 m), the sierra (2,500-3,500 m), and the altiplano (above 4,200 m). After isolation of altitude from other environmental factors (age, sex, body build, ethnicity, smoking, and residential permanence), an increase in 2,3-diphosphoglycerate and a decrease in adenosine triphosphate was observed. Both hemoglobin and hematocrit increased as expected, but mean cell hemoglobin concentration declined. It is proposed that a decline in the activity of a single enzyme, pyruvate kinase, can account for these observed changes and suggests a pivotal role for pyruvate kinase in the physiological adaptation to altitude hypoxia.

  11. Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction

    PubMed Central

    Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600–4,100 m) residents aged 18–25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. PMID:26092986

  12. Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

    PubMed

    Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

    2015-08-15

    Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  13. Transthoracic Electrical Impedance in Cases of High-altitude Hypoxia

    PubMed Central

    Roy, Sujoy B.; Balasubramanian, V.; Khan, M. R.; Kaushik, V. S.; Manchanda, S. C.; Guha, S. K.

    1974-01-01

    Changes in transthoracic electrical impedance (T.E.I.) due to high-altitude hypoxia (3,658 m) have been measured in 20 young, healthy Indian soldiers. They were first studied at sea level (198 m) and then rapidly transported by air to 3,658 m, where they were studied daily from day 1 to day 5 and then on days 8 and 10. The mean (±S.D.) T.E.I. at sea level (34·6±0·6Ω) fell sharply to 29·6±0·8Ω, 30·3±0·9Ω, and 30·5±1·1Ω on days 1, 2, and 3 (P <0·001) and levelled off at 31·5±0·7Ω on day 10, which was comparable to the mean value obtained in 13 persons permanently resident at high altitude (32·2±0·7Ω). Five sea-level residents who had acute mountain sickness (A.M.S.) or high-altitude pulmonary oedema (H.A.P.O.) had a still lower mean value (22·5±1·1Ω). One normal healthy subject who at sea level had a T.E.I. of 34·7Ω developed H.A.P.O. when the T.E.I. fell to 21·1Ω. Ninety minutes after the administration of 80 mg of intravenous frusemide the value increased to 35·5Ω. In another subject with A.M.S. who received 40 mg of frusemide intravenously the T.E.I. rose from 21·9 to 33·2Ω. Since the study was non-invasive the changes in impedance could not be correlated objectively with alterations in either pulmonary blood volume or pulmonary extravascular water space. In the subject, however, with x-ray evidence of H.A.P.O. and a low T.E.I. intravenous frusemide produced a marked rise in T.E.I. together with clearing of the chest x-ray picture within 24 hours, indicating an inverse relationship between impedance and thoracic fluid volume. It is suggested that with further objective verification in man the measurement of T.E.I. may be a potentially promising technique for the early detection of increased pulmonary fluid volume. ImagesFIG. 3FIG. 4 PMID:4416705

  14. High altitude hypoxia as a factor that promotes tibial growth plate development in broiler chickens

    PubMed Central

    Huang, Shucheng; Zhang, Lihong; Rehman, Mujeeb Ur; Iqbal, Muhammad Kashif; Lan, Yanfang; Mehmood, Khalid; Zhang, Hui; Qiu, Gang; Nabi, Fazul; Yao, Wangyuan; Wang, Meng; Li, Jiakui

    2017-01-01

    Tibial dyschondroplasia (TD) is one of the most common problems in the poultry industry and leads to lameness by affecting the proximal growth plate of the tibia. However, due to the unique environmental and geographical conditions of Tibet, no case of TD has been reported in Tibetan chickens (TBCs). The present study was designed to investigate the effect of high altitude hypoxia on blood parameters and tibial growth plate development in chickens using the complete blood count, morphology, and histological examination. The results of this study showed an undesirable impact on the overall performance, body weight, and mortality of Arbor Acres chickens (AACs) exposed to a high altitude hypoxic environment. However, AACs raised under hypoxic conditions showed an elevated number of red blood cells (RBCs) and an increase in hemoglobin and hematocrit values on day 14 compared to the hypobaric normoxia group. Notably, the morphology and histology analyses showed that the size of tibial growth plates in AACs was enlarged and that the blood vessel density was also higher after exposure to the hypoxic environment for 14 days, while no such change was observed in TBCs. Altogether, our results revealed that the hypoxic environment has a potentially new role in increasing the blood vessel density of proximal tibial growth plates to strengthen and enhance the size of the growth plates, which may provide new insights for the therapeutic manipulation of hypoxia in poultry TD. PMID:28282429

  15. High-intensity intermittent exercise increases pulmonary interstitial edema at altitude but not at simulated altitude.

    PubMed

    Edsell, Mark E; Wimalasena, Yashvi H; Malein, William L; Ashdown, Kimberly M; Gallagher, Carla A; Imray, Chris H; Wright, Alex D; Myers, Stephen D

    2014-12-01

    Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders. Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines. After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours. HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  16. Mast cells in the human lung at high altitude

    NASA Astrophysics Data System (ADS)

    Heath, Donald

    1992-12-01

    Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.

  17. A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude

    PubMed Central

    Boos, Christopher John; O’Hara, John Paul; Mellor, Adrian; Hodkinson, Peter David; Tsakirides, Costas; Reeve, Nicola; Gallagher, Liam; Green, Nicholas Donald Charles; Woods, David Richard

    2016-01-01

    Background There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses. Materials and Methods This was a prospective observational study of 14 healthy subjects aged 22–35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA. Results All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise. Conclusions GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function. PMID:27100313

  18. Exhaled volatile organic compounds in individuals with a history of high altitude pulmonary edema and varying hypoxia-induced responses.

    PubMed

    Figueroa, Jennifer A; Mansoor, Jim K; Allen, Roblee P; Davis, Cristina E; Walby, William F; Aksenov, Alexander A; Zhao, Weixiang; Lewis, William R; Schelegle, Edward S

    2015-04-20

    With ascent to altitude, certain individuals are susceptible to high altitude pulmonary edema (HAPE), which in turn can cause disability and even death. The ability to identify individuals at risk of HAPE prior to ascent is poor. The present study examined the profile of volatile organic compounds (VOC) in exhaled breath condensate (EBC) and pulmonary artery systolic pressures (PASP) before and after exposure to normobaric hypoxia (12% O2) in healthy males with and without a history of HAPE (Hx HAPE, n = 5; Control, n = 11). In addition, hypoxic ventilatory response (HVR), and PASP response to normoxic exercise were also measured. Auto-regression/partial least square regression of whole gas chromatography/mass spectrometry (GC/MS) data and binary logistic regression (BLR) of individual GC peaks and physiologic parameters resulted in models that separate individual subjects into their groups with variable success. The result of BLR analysis highlights HVR, PASP response to hypoxia and the amount of benzyl alcohol and dimethylbenzaldehyde dimethyl in expired breath as markers of HAPE history. These findings indicate the utility of EBC VOC analysis to discriminate between individuals with and without a history of HAPE and identified potential novel biomarkers that correlated with physiological responses to hypoxia.

  19. Evolved changes in the intracellular distribution and physiology of muscle mitochondria in high-altitude native deer mice.

    PubMed

    Mahalingam, Sajeni; McClelland, Grant B; Scott, Graham R

    2017-07-15

    Mitochondrial function changes over time at high altitudes, but the potential benefits of these changes for hypoxia resistance remains unclear. We used high-altitude-adapted populations of deer mice, which exhibit enhanced aerobic performance in hypoxia, to examine whether changes in mitochondrial physiology or intracellular distribution in the muscle contribute to hypoxia resistance. Permeabilized muscle fibres from the gastrocnemius muscle had higher respiratory capacities in high-altitude mice than in low-altitude mice. Highlanders also had higher mitochondrial volume densities, due entirely to an enriched abundance of subsarcolemmal mitochondria, such that more mitochondria were situated near the cell membrane and adjacent to capillaries. There were several effects of hypoxia acclimation on mitochondrial function, some of which were population specific, but they differed from the evolved changes in high-altitude natives, which probably provide a better indication of adaptive traits that improve performance and hypoxia resistance at high altitudes. High-altitude natives that have evolved to live in hypoxic environments provide a compelling system to understand how animals can overcome impairments in oxygen availability. We examined whether these include changes in mitochondrial physiology or intracellular distribution that contribute to hypoxia resistance in high-altitude deer mice (Peromyscus maniculatus). Mice from populations native to high and low altitudes were born and raised in captivity, and as adults were acclimated to normoxia or hypobaric hypoxia (equivalent to 4300 m elevation). We found that highlanders had higher respiratory capacities in the gastrocnemius (but not soleus) muscle than lowlanders (assessed using permeabilized fibres with single or multiple inputs to the electron transport system), due in large part to higher mitochondrial volume densities in the gastrocnemius. The latter was attributed to an increased abundance of subsarcolemmal

  20. The autonomic nervous system at high altitude

    PubMed Central

    Drinkhill, Mark J.; Rivera-Chira, Maria

    2007-01-01

    The effects of hypobaric hypoxia in visitors depend not only on the actual elevation but also on the rate of ascent. Sympathetic activity increases and there are increases in blood pressure and heart rate. Pulmonary vasoconstriction leads to pulmonary hypertension, particularly during exercise. The sympathetic excitation results from hypoxia, partly through chemoreceptor reflexes and partly through altered baroreceptor function. High pulmonary arterial pressures may also cause reflex systemic vasoconstriction. Most permanent high altitude dwellers show excellent adaptation although there are differences between populations in the extent of the ventilatory drive and the erythropoiesis. Some altitude dwellers, particularly Andeans, may develop chronic mountain sickness, the most prominent characteristic of which being excessive polycythaemia. Excessive hypoxia due to peripheral chemoreceptor dysfunction has been suggested as a cause. The hyperviscous blood leads to pulmonary hypertension, symptoms of cerebral hypoperfusion, and eventually right heart failure and death. PMID:17264976

  1. Why Are High Altitude Natives So Strong at High Altitude? Nature vs. Nurture: Genetic Factors vs. Growth and Development.

    PubMed

    Brutsaert, Tom

    Among high-altitude natives there is evidence of a general hypoxia tolerance leading to enhanced performance and/or increased capacity in several important domains. These domains likely include an enhanced physical work capacity, an enhanced reproductive capacity, and an ability to resist several common pathologies of chronic high-altitude exposure. The "strength" of the high-altitude native in this regard may have both a developmental and a genetic basis, although there is better evidence for the former (developmental effects) than for the latter. For example, early-life hypoxia exposure clearly results in lung growth and remodeling leading to an increased O2 diffusing capacity in adulthood. Genetic research has yet to reveal a population genetic basis for enhanced capacity in high-altitude natives, but several traits are clearly under genetic control in Andean and Tibetan populations e.g., resting and exercise arterial O2 saturation (SaO2). This chapter reviews the effects of nature and nurture on traits that are relevant to the process of gas exchange, including pulmonary volumes and diffusion capacity, the maximal oxygen consumption (VO2max), the SaO2, and the alveolar-arterial oxygen partial pressure difference (A-aDO2) during exercise.

  2. Can patients with pulmonary hypertension travel to high altitude?

    PubMed

    Luks, Andrew M

    2009-01-01

    With the increasing popularity of adventure travel and mountain activities, it is likely that many high altitude travelers will have underlying medical problems and approach clinicians for advice about ensuring a safe sojourn. Patients with underlying pulmonary hypertension are one group who warrants significant concern during high altitude travel, because ambient hypoxia at high altitude will trigger hypoxic pulmonary vasoconstriction and cause further increases in pulmonary artery (PA) pressure, which may worsen hemodynamics and also predispose to acute altitude illness. After addressing basic information about pulmonary hypertension and pulmonary vascular responses to acute hypoxia, this review discusses the evidence supporting an increased risk for high altitude pulmonary edema in these patients, concerns regarding worsening oxygenation and right-heart function, the degree of underlying pulmonary hypertension necessary to increase risk, and the altitude at which such problems may occur. These patients may be able to travel to high altitude, but they require careful pre-trip assessment, including echocardiography and, when feasible, high altitude simulation testing with echocardiography to assess changes in PA pressure and oxygenation under hypoxic conditions. Those with mean PA pressure > or =35 mm Hg or systolic PA pressure > or =50 mm Hg at baseline should avoid travel to >2000 m; but if such travel is necessary or strongly desired, they should use supplemental oxygen during the sojourn. Patients with milder degrees of pulmonary hypertension may travel to altitudes <3000 m, but should consider prophylactic measures, including pulmonary vasodilators or supplemental oxygen.

  3. Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland

    PubMed Central

    Okumiya, Kiyohito; Sakamoto, Ryota; Ishimoto, Yasuko; Kimura, Yumi; Fukutomi, Eriko; Ishikawa, Motonao; Suwa, Kuniaki; Imai, Hissei; Chen, Wenling; Kato, Emiko; Nakatsuka, Masahiro; Kasahara, Yoriko; Fujisawa, Michiko; Wada, Taizo; Wang, Hongxin; Dai, Qingxiang; Xu, Huining; Qiao, Haisheng; Ge, Ri-Li; Norboo, Tsering; Tsering, Norboo; Kosaka, Yasuyuki; Nose, Mitsuhiro; Yamaguchi, Takayoshi; Tsukihara, Toshihiro; Ando, Kazuo; Inamura, Tetsuya; Takeda, Shinya; Ishine, Masayuki; Otsuka, Kuniaki; Matsubayashi, Kozo

    2016-01-01

    Objectives To clarify the association between glucose intolerance and high altitudes (2900–4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. Design Cross-sectional epidemiological study on Tibetan highlanders. Participants We enrolled 1258 participants aged 40–87 years. The rural population comprised farmers in Domkhar (altitude 2900–3800 m) and nomads in Haiyan (3000–3100 m), Ryuho (4400 m) and Changthang (4300–4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). Main outcome measure Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. Results The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500–4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. Conclusions Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose

  4. 'Ome' on the range: update on high-altitude acclimatization/adaptation and disease.

    PubMed

    Luo, Yongjun; Wang, Yuxiao; Lu, Hongxiang; Gao, Yuqi

    2014-11-01

    The main physiological challenge in high-altitude plateau environments is hypoxia. When people living in a plain environment migrate to the plateau, they face the threat of hypoxia. Most people can acclimatize to high altitudes; the acclimatization process mainly consists of short-term hyperventilation and long-term compensation by increased oxygen uptake, transport, and use due to increased red blood cell mass, myoglobin, and mitochondria. If individuals cannot acclimatize to high altitude, they may suffer from a high-altitude disease, such as acute mountain disease (AMS), high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE) or chronic mountain sickness (CMS). Because some individuals are more susceptible to high altitude diseases than others, the incidence of these high-altitude diseases is variable and cannot be predicted. Studying "omes" using genomics, proteomics, metabolomics, transcriptomics, lipidomics, immunomics, glycomics and RNomics can help us understand the factors that mediate susceptibility to high altitude illnesses. Moreover, analysis of the "omes" using a systems biology approach may provide a greater understanding of high-altitude illness pathogenesis and improve the efficiency of the diagnosis and treatment of high-altitude illnesses in the future. Below, we summarize the current literature regarding the role of "omes" in high-altitude acclimatization/adaptation and disease and discuss key research gaps to better understand the contribution of "omes" to high-altitude illness susceptibility.

  5. Epigenomics and human adaptation to high altitude.

    PubMed

    Julian, Colleen G

    2017-11-01

    Over the past decade, major technological and analytical advancements have propelled efforts toward identifying the molecular mechanisms that govern human adaptation to high altitude. Despite remarkable progress with respect to the identification of adaptive genomic signals that are strongly associated with the "hypoxia-tolerant" physiological characteristics of high-altitude populations, many questions regarding the fundamental biological processes underlying human adaptation remain unanswered. Vital to address these enduring questions will be determining the role of epigenetic processes, or non-sequence-based features of the genome, that are not only critical for the regulation of transcriptional responses to hypoxia but heritable across generations. This review proposes that epigenomic processes are involved in shaping patterns of adaptation to high altitude by influencing adaptive potential and phenotypic variability under conditions of limited oxygen supply. Improved understanding of the interaction between genetic, epigenetic, and environmental factors holds great promise to provide deeper insight into the mechanisms underlying human adaptive potential, and clarify its implications for biomedical research. Copyright © 2017 the American Physiological Society.

  6. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    PubMed Central

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491

  7. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    NASA Astrophysics Data System (ADS)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  8. Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans.

    PubMed

    Crawford, Jacob E; Amaru, Ricardo; Song, Jihyun; Julian, Colleen G; Racimo, Fernando; Cheng, Jade Yu; Guo, Xiuqing; Yao, Jie; Ambale-Venkatesh, Bharath; Lima, João A; Rotter, Jerome I; Stehlik, Josef; Moore, Lorna G; Prchal, Josef T; Nielsen, Rasmus

    2017-11-02

    The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia. In contrast, high-altitude-adapted Quechua- and Aymara-speaking inhabitants of the Andean Altiplano are not protected from high-altitude polycythemia in the same way, yet they exhibit other adaptive features for which the genetic underpinnings remain obscure. Here, we used whole-genome sequencing to scan high-altitude Andeans for signals of selection. The genes showing the strongest evidence of selection-including BRINP3, NOS2, and TBX5-are associated with cardiovascular development and function but are not in the response-to-hypoxia pathway. Using association mapping, we demonstrated that the haplotypes under selection are associated with phenotypic variations related to cardiovascular health. We hypothesize that selection in response to hypoxia in Andeans could have vascular effects and could serve to mitigate the deleterious effects of polycythemia rather than reduce polycythemia itself. Copyright © 2017. Published by Elsevier Inc.

  9. Preacclimatization in hypoxic chambers for high altitude sojourns.

    PubMed

    Küpper, Thomas E A H; Schöffl, Volker

    2010-09-01

    Since hypoxic chambers are more and more available, they are used for preacclimatization to prepare for sojourns at high altitude. Since there are different protocols and the data differ, there is no general consensus about the standard how to perform preacclimatization by simulated altitude. The paper reviews the different types of exposure and focuses on the target groups which may benefit from preacclimatization. Since data about intermittent hypoxia for some hours per day to reduce the incidence of acute mountain sickness differ, it is suggested to perform preacclimatization by sleeping some nights at a simulated altitude which follows the altitude profile of the "gold standard" for high altitude acclimatization.

  10. Transcriptomic analysis provides insight into high-altitude acclimation in domestic goats.

    PubMed

    Tang, Qianzi; Huang, Wenyao; Guan, Jiuqiang; Jin, Long; Che, Tiandong; Fu, Yuhua; Hu, Yaodong; Tian, Shilin; Wang, Dawei; Jiang, Zhi; Li, Xuewei; Li, Mingzhou

    2015-08-10

    Domestic goats are distributed in a wide range of habitats and have acclimated to their local environmental conditions. To investigate the gene expression changes of goats that are induced by high altitude stress, we performed RNA-seq on 27 samples from the three hypoxia-sensitive tissues (heart, lung, and skeletal muscle) in three indigenous populations from distinct altitudes (600 m, 2000 m, and 3000 m). We generated 129Gb of high-quality sequencing data (~4Gb per sample) and catalogued the expression profiles of 12,421 annotated hircine genes in each sample. The analysis showed global similarities and differences of high-altitude transcriptomes among populations and tissues as well as revealed that the heart underwent the most high-altitude induced expression changes. We identified numerous differentially expressed genes that exhibited distinct expression patterns, and nonsynonymous single nucleotide variant-containing genes that were highly differentiated between the high- and low-altitude populations. These genes have known or potential roles in hypoxia response and were enriched in functional gene categories potentially responsible for high-altitude stress. Therefore, they are appealing candidates for further investigation of the gene expression and associated regulatory mechanisms related to high-altitude acclimation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The yak genome and adaptation to life at high altitude.

    PubMed

    Qiu, Qiang; Zhang, Guojie; Ma, Tao; Qian, Wubin; Wang, Junyi; Ye, Zhiqiang; Cao, Changchang; Hu, Quanjun; Kim, Jaebum; Larkin, Denis M; Auvil, Loretta; Capitanu, Boris; Ma, Jian; Lewin, Harris A; Qian, Xiaoju; Lang, Yongshan; Zhou, Ran; Wang, Lizhong; Wang, Kun; Xia, Jinquan; Liao, Shengguang; Pan, Shengkai; Lu, Xu; Hou, Haolong; Wang, Yan; Zang, Xuetao; Yin, Ye; Ma, Hui; Zhang, Jian; Wang, Zhaofeng; Zhang, Yingmei; Zhang, Dawei; Yonezawa, Takahiro; Hasegawa, Masami; Zhong, Yang; Liu, Wenbin; Zhang, Yan; Huang, Zhiyong; Zhang, Shengxiang; Long, Ruijun; Yang, Huanming; Wang, Jian; Lenstra, Johannes A; Cooper, David N; Wu, Yi; Wang, Jun; Shi, Peng; Wang, Jian; Liu, Jianquan

    2012-07-01

    Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

  12. Shilajit: A panacea for high-altitude problems

    PubMed Central

    Meena, Harsahay; Pandey, H. K.; Arya, M. C.; Ahmed, Zakwan

    2010-01-01

    High altitude problems like hypoxia, acute mountain sickness, high altitude cerebral edema, pulmonary edema, insomnia, tiredness, lethargy, lack of appetite, body pain, dementia, and depression may occur when a person or a soldier residing in a lower altitude ascends to high-altitude areas. These problems arise due to low atmospheric pressure, severe cold, high intensity of solar radiation, high wind velocity, and very high fluctuation of day and night temperatures in these regions. These problems may escalate rapidly and may sometimes become life-threatening. Shilajit is a herbomineral drug which is pale-brown to blackish-brown, is composed of a gummy exudate that oozes from the rocks of the Himalayas in the summer months. It contains humus, organic plant materials, and fulvic acid as the main carrier molecules. It actively takes part in the transportation of nutrients into deep tissues and helps to overcome tiredness, lethargy, and chronic fatigue. Shilajit improves the ability to handle high altitudinal stresses and stimulates the immune system. Thus, Shilajit can be given as a supplement to people ascending to high-altitude areas so that it can act as a “health rejuvenator” and help to overcome high-altitude related problems. PMID:20532096

  13. Shilajit: A panacea for high-altitude problems.

    PubMed

    Meena, Harsahay; Pandey, H K; Arya, M C; Ahmed, Zakwan

    2010-01-01

    High altitude problems like hypoxia, acute mountain sickness, high altitude cerebral edema, pulmonary edema, insomnia, tiredness, lethargy, lack of appetite, body pain, dementia, and depression may occur when a person or a soldier residing in a lower altitude ascends to high-altitude areas. These problems arise due to low atmospheric pressure, severe cold, high intensity of solar radiation, high wind velocity, and very high fluctuation of day and night temperatures in these regions. These problems may escalate rapidly and may sometimes become life-threatening. Shilajit is a herbomineral drug which is pale-brown to blackish-brown, is composed of a gummy exudate that oozes from the rocks of the Himalayas in the summer months. It contains humus, organic plant materials, and fulvic acid as the main carrier molecules. It actively takes part in the transportation of nutrients into deep tissues and helps to overcome tiredness, lethargy, and chronic fatigue. Shilajit improves the ability to handle high altitudinal stresses and stimulates the immune system. Thus, Shilajit can be given as a supplement to people ascending to high-altitude areas so that it can act as a "health rejuvenator" and help to overcome high-altitude related problems.

  14. [Neuropsychological modifications at high altitude: from Pamir to Karakorum].

    PubMed

    Nardi, Bernardo; Brandoni, Marco; Capecci, Ilaria; Castellani, Simona; Rupoli, Sara; Bellantuono, Cesario

    2009-01-01

    Neuropsychological modifications and acclimatization processes at over 8000 without auxiliary oxygen were investigated in two climbers, evaluating attentive abilities and matching their performances. During rest in base-camp (4800 m), at other three Resorts - Resort I (5800 m), Resort II (6400 m), Resort III (7200 m) -, and four months after the return at low altitude, were administered: Temporal Orientation Test (TOT), Trail Making Test (TMT), Animal Naming (AN), Verbal Fluency Test (VFT), Arithmetical Judgment Test (AJT), and Drawing Test (DT). Results. At TOT and at AJT, both the climbers demonstrated scores at higher normal levels (Eq = 4) in all the Resorts in which they were performed. They showed an impairment at AN test, especially at Resort III, showing sensitivity of animal naming to hypoxia. At the DT, human figures were reduced in their dimensions and details, as consequence of the tendency to self closure and introversion that occurs at higher altitudes. Neuropsychological functions concerning verbal fluency showed sensitivity to hypoxia, especially at higher altitudes. TMT demonstrated that attentive ability can be preserved if acclimatization is good. Sensitivity to hypoxia and acclimatization processes showed a significant subjective variability. The results of this study show that exposure to high altitude produces some significant neuropsychological changes.

  15. Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

    PubMed

    Longo, Lawrence D; Pearce, William J

    2005-01-01

    During the past several decades, many risk factors for cerebrovascular and cardiovascular disease have been identified. More recently, it has been appreciated that inadequate nutrition and/or other intrauterine factors during fetal development may play an important role in the genesis of these conditions. An additional stress factor that may "program" the fetus for disease later in life is chronic hypoxia. In studies originally designed to examine the function of developing cerebral arterial function in response to long-term hypoxia (LTH), it has become clear that many cellular and subcellular changes may have important implications for later life. Here we review some of the significant alterations in fetal cerebral artery structure and function induced by high-altitude (3,820 m, 12,470 ft) LTH ( approximately 110 days). LTH is associated with augmentation or upregulation of presynaptic functions, including responses to perivascular (i.e., sympathetic) nerve stimulation, and structural maturational changes. In contrast, many postsynaptic functions related to the Ca(2+)-dependent contractile pathway tend to be downregulated, whereas elements of the Ca(2+)-independent contraction pathway are upregulated. The results emphasize the role of high-altitude LTH in modulating many aspects of electromechanical and pharmacomechanical coupling in the developing cerebral vasculature. A complicating factor is that the regulation of cerebrovascular tone by Ca(2+)-dependent and Ca(2+)-independent pathways changes significantly as a function of maturational age. In addition to highlighting independent regulation of various elements of the signal transduction cascade, the studies demonstrate the potential for LTH to program the fetus for cerebrovascular and other disease as an adult.

  16. Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

    PubMed

    Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin

    2016-04-01

    Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Early history of high-altitude physiology.

    PubMed

    West, John B

    2016-02-01

    High-altitude physiology can be said to have begun in 1644 when Torricelli described the first mercury barometer and wrote the immortal words "We live submerged at the bottom of an ocean of the element air." Interestingly, the notion of atmospheric pressure had eluded his teacher, the great Galileo. Blaise Pascal was responsible for describing the fall in pressure with increasing altitude, and Otto von Guericke gave a dramatic demonstration of the enormous force that could be developed by atmospheric pressure. Robert Boyle learned of Guericke's experiment and, with Robert Hooke, constructed the first air pump that allowed small animals to be exposed to a low pressure. Hooke also constructed a small low-pressure chamber and exposed himself to a simulated altitude of about 2400 meters. With the advent of ballooning, humans were rapidly exposed to very low pressures, sometimes with tragic results. For example, the French balloon, Zénith, rose to over 8000 m, and two of the three aeronauts succumbed to the hypoxia. Paul Bert was the first person to clearly state that the deleterious effects of high altitude were caused by the low partial pressure of oxygen (PO2), and later research was accelerated by high-altitude stations and expeditions to high altitude. © 2015 New York Academy of Sciences.

  18. Comparative transcriptomics of 5 high-altitude vertebrates and their low-altitude relatives

    PubMed Central

    Tang, Qianzi; Zhou, Xuming; Jin, Long; Guan, Jiuqiang; Liu, Rui; Li, Jing; Long, Kereng; Tian, Shilin; Che, Tiandong; Hu, Silu; Liang, Yan; Yang, Xuemei; Tao, Xuan; Zhong, Zhijun; Wang, Guosong; Chen, Xiaohui; Li, Diyan; Ma, Jideng; Wang, Xun; Mai, Miaomiao; Jiang, An’an; Luo, Xiaolin; Lv, Xuebin; Gladyshev, Vadim N; Li, Xuewei

    2017-01-01

    Abstract Background Species living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that have examined high-altitude adaptation have identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown. Findings We generated a total of 910 Gb of high-quality RNA-seq data for 180 samples derived from 6 tissues of 5 agriculturally important high-altitude vertebrates (Tibetan chicken, Tibetan pig, Tibetan sheep, Tibetan goat, and yak) and their cross-fertile relatives living in geographically neighboring low-altitude regions. Of these, ∼75% reads could be aligned to their respective reference genomes, and on average ∼60% of annotated protein coding genes in each organism showed FPKM expression values greater than 0.5. We observed a general concordance in topological relationships between the nucleotide alignments and gene expression–based trees. Tissue and species accounted for markedly more variance than altitude based on either the expression or the alternative splicing patterns. Cross-species clustering analyses showed a tissue-dominated pattern of gene expression and a species-dominated pattern for alternative splicing. We also identified numerous differentially expressed genes that could potentially be involved in phenotypic divergence shaped by high-altitude adaptation. Conclusions These data serve as a valuable resource for examining the convergence and divergence of gene expression changes between species as they adapt or acclimatize to high-altitude environments. PMID:29149296

  19. Comparative transcriptomics of 5 high-altitude vertebrates and their low-altitude relatives.

    PubMed

    Tang, Qianzi; Gu, Yiren; Zhou, Xuming; Jin, Long; Guan, Jiuqiang; Liu, Rui; Li, Jing; Long, Kereng; Tian, Shilin; Che, Tiandong; Hu, Silu; Liang, Yan; Yang, Xuemei; Tao, Xuan; Zhong, Zhijun; Wang, Guosong; Chen, Xiaohui; Li, Diyan; Ma, Jideng; Wang, Xun; Mai, Miaomiao; Jiang, An'an; Luo, Xiaolin; Lv, Xuebin; Gladyshev, Vadim N; Li, Xuewei; Li, Mingzhou

    2017-12-01

    Species living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that have examined high-altitude adaptation have identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown. We generated a total of 910 Gb of high-quality RNA-seq data for 180 samples derived from 6 tissues of 5 agriculturally important high-altitude vertebrates (Tibetan chicken, Tibetan pig, Tibetan sheep, Tibetan goat, and yak) and their cross-fertile relatives living in geographically neighboring low-altitude regions. Of these, ∼75% reads could be aligned to their respective reference genomes, and on average ∼60% of annotated protein coding genes in each organism showed FPKM expression values greater than 0.5. We observed a general concordance in topological relationships between the nucleotide alignments and gene expression-based trees. Tissue and species accounted for markedly more variance than altitude based on either the expression or the alternative splicing patterns. Cross-species clustering analyses showed a tissue-dominated pattern of gene expression and a species-dominated pattern for alternative splicing. We also identified numerous differentially expressed genes that could potentially be involved in phenotypic divergence shaped by high-altitude adaptation. These data serve as a valuable resource for examining the convergence and divergence of gene expression changes between species as they adapt or acclimatize to high-altitude environments. © The Authors 2017. Published by Oxford University Press.

  20. The effects of energy beverages in counteracting the symptoms of mild hypoxia at legal general aviation altitudes

    NASA Astrophysics Data System (ADS)

    Bull, Daniel Mark

    The purpose of this thesis was to conduct preliminary research, in the form of a pilot study, concerning the natural effects of hypoxia compared to the effects of hypoxia experienced after the consumption of an energy beverage. The study evaluated the effects of hypoxia on FAA certificated pilots at a simulated legal general aviation altitude, utilizing the normobaric High Altitude Lab (HAL) located at Embry Riddle Aeronautical University, Daytona Beach, Florida. The researcher tested 11 subjects, who completed three simulated flight tasks within the HAL using the Frasca International Mentor Advanced Aviation Training Device (AATD). The flight tasks were completed after consuming Red BullRTM, MonsterRTM , or a placebo beverage. The researcher derived three test variables from core outputs of the AATD: lateral deviations from the glide slope, vertical deviations from the localizer, and airspeed deviations from the target speed of 100 knots. A repeated-measures ANOVA was carried out to determine effects of the beverages on the test variables. While results were non-significant, the researcher concluded that further research should be conducted with a larger sample.

  1. Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

    PubMed Central

    2009-01-01

    High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude. PMID:20038496

  2. Mechanisms of Memory Dysfunction during High Altitude Hypoxia Training in Military Aircrew.

    PubMed

    Nation, Daniel A; Bondi, Mark W; Gayles, Ellis; Delis, Dean C

    2017-01-01

    Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1-10).

  3. Physiological effects of intermittent hypoxia.

    PubMed

    Powell, F L; Garcia, N

    2000-01-01

    Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

  4. Heat shock response and mammal adaptation to high elevation (hypoxia).

    PubMed

    Wang, Xiaolin; Xu, Cunshuan; Wang, Xiujie; Wang, Dongjie; Wang, Qingshang; Zhang, Baochen

    2006-10-01

    The mammal's high elevation (hypoxia) adaptation was studied by using the immunological and the molecular biological methods to understand the significance of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal heat shock response. (1) From high elevation to low elevation (natural hypoxia): Western blot and conventional RT-PCR and real-time fluorescence quota PCR were adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural expression of brain tissue of Hsp70 gene was determined in the cardiac muscle tissue among the different elevation mammals (yak). (2) From low elevation to high elevation (hypoxia induction): The mammals (domestic rabbits) from the low elevation were sent directly to the areas with different high elevations like 2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before being slaughtered and the genetic inductive expression of the brain tissue of Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at different elevations possessed their heat shock response gene. Hsp70 of the high elevation mammal rose abruptly under stress and might be induced to come into being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process of heat shock response is suitable to maintain the cells' normal physiological functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m above sea level is the best condition for the heat shock response, and it starts to reduce when the altitude is over 6000 m above sea level. The Hsp70 production quantity and the cell hypoxia bearing capacity have their direct ratio.

  5. Yak response to high-altitude hypoxic stress by altering mRNA expression and DNA methylation of hypoxia-inducible factors.

    PubMed

    Xiong, Xianrong; Fu, Mei; Lan, Daoliang; Li, Jian; Zi, Xiangdong; Zhong, Jincheng

    2015-01-01

    Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators, which play crucial roles in tumor angiogenesis and mammalian development, and regulate the transcription of genes involved in oxygen homeostasis in response to hypoxia. However, information on HIF-1α and HIF-2α in yak (Bos grunniens) is scarce. The complete coding region of yak HIF-2α was cloned, its mRNA expression in several tissues were determined, and the expression levels were compared with those of closely related low-altitude cattle (Bos taurus), and the methylation status of promoter regions were analyzed to better understand the roles of HIF-1α and HIF-2α in domesticated yak. The yak HIF-2α cDNA was cloned and sequenced in the present work reveals the evolutionary conservation through multiple sequence alignment, although 15 bases changed, resulting in 8 amino acid substitutions in the translated proteins in cattle. The tissue-specific expression results showed that HIF-1α is ubiquitously expressed, whereas HIF-2α expression is limited to endothelial tissues (kidney, heart, lung, spleen, and liver) and blood in yak. Both HIF-1α and HIF-2α expressions were higher in yak tissues than in cattle. The HIF-1α expression level is much higher in yak than cattle in these organs, except for the lung (P < 0.05), but the HIF-2α gene is significantly different in the heart, spleen, and kidney (P < 0.05). Furthermore, the methylation levels in the 5' flanking regulatory regions of HIF-1α and HIF-2α in yak kidney were significantly decreased than cattle counterparts (P < 0.05). Identifying these genes and the comparison of different expressions facilitates the understanding of the biological high-altitude hypoxic stress response mechanism and may assist current medical research to understand hypoxia-related diseases.

  6. Population variation revealed high-altitude adaptation of Tibetan mastiffs.

    PubMed

    Li, Yan; Wu, Dong-Dong; Boyko, Adam R; Wang, Guo-Dong; Wu, Shi-Fang; Irwin, David M; Zhang, Ya-Ping

    2014-05-01

    With the assistance of their human companions, dogs have dispersed into new environments during the expansion of human civilization. Tibetan Mastiff (TM), a native of the Tibetan Plateau, was derived from the domesticated Chinese native dog and, like Tibetans, has adapted to the extreme environment of high altitude. Here, we genotyped genome-wide single-nucleotide polymorphisms (SNPs) from 32 TMs and compared them with SNPs from 20 Chinese native dogs and 14 gray wolves (Canis lupus). We identified 16 genes with signals of positive selection in the TM, with 12 of these candidate genes associated with functions that have roles in adaptation to high-altitude adaptation, such as EPAS1, SIRT7, PLXNA4, and MAFG that have roles in responses to hypoxia. This study provides important information on the genetic diversity of the TM and potential mechanisms for adaptation to hypoxia.

  7. Impact of extreme exercise at high altitude on oxidative stress in humans.

    PubMed

    Quindry, John; Dumke, Charles; Slivka, Dustin; Ruby, Brent

    2016-09-15

    Exercise and oxidative stress research continues to grow as a physiological subdiscipline. The influence of high altitude on exercise and oxidative stress is among the recent topics of intense study in this area. Early findings indicate that exercise at high altitude has an independent influence on free radical generation and the resultant oxidative stress. This review provides a detailed summary of oxidative stress biochemistry as gleaned mainly from studies of humans exercising at high altitude. Understanding of the human response to exercise at altitude is largely derived from field-based research at altitudes above 3000 m in addition to laboratory studies which employ normobaric hypoxia. The implications of oxidative stress incurred during high altitude exercise appear to be a transient increase in oxidative damage followed by redox-sensitive adaptations in multiple tissues. These outcomes are consistent for lowland natives, high altitude acclimated sojourners and highland natives, although the latter group exhibits a more robust adaptive response. To date there is no evidence that altitude-induced oxidative stress is deleterious to normal training or recovery scenarios. Limited evidence suggests that deleterious outcomes related to oxidative stress are limited to instances where individuals are exposed to extreme elevations for extended durations. However, confirmation of this tentative conclusion requires further investigation. More applicably, altitude-induced hypoxia may have an independent influence on redox-sensitive adaptive responses to exercise and exercise recovery. If correct, these findings may hold important implications for athletes, mountaineers, and soldiers working at high altitude. These points are raised within the confines of published research on the topic of oxidative stress during exercise at altitude. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  8. Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice

    PubMed Central

    Stobdan, Tsering; Zhou, Dan; Ao-Ieong, Eilleen; Ortiz, Daniel; Ronen, Roy; Hartley, Iain; Gan, Zhuohui; McCulloch, Andrew D.; Bafna, Vineet; Cabrales, Pedro; Haddad, Gabriel G.

    2015-01-01

    To better understand human adaptation to stress, and in particular to hypoxia, we took advantage of one of nature’s experiments at high altitude (HA) and studied Ethiopians, a population that is well-adapted to HA hypoxic stress. Using whole-genome sequencing, we discovered that EDNRB (Endothelin receptor type B) is a candidate gene involved in HA adaptation. To test whether EDNRB plays a critical role in hypoxia tolerance and adaptation, we generated EdnrB knockout mice and found that when EdnrB−/+ heterozygote mice are treated with lower levels of oxygen (O2), they tolerate various levels of hypoxia (even extreme hypoxia, e.g., 5% O2) very well. For example, they maintain ejection fraction, cardiac contractility, and cardiac output in severe hypoxia. Furthermore, O2 delivery to vital organs was significantly higher and blood lactate was lower in EdnrB−/+ compared with wild type in hypoxia. Tissue hypoxia in brain, heart, and kidney was lower in EdnrB−/+ mice as well. These data demonstrate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Transcriptomic profiling of left ventricles revealed three specific genes [natriuretic peptide type A (Nppa), sarcolipin (Sln), and myosin light polypeptide 4 (Myl4)] that were oppositely expressed (q < 0.05) between EdnrB−/+ and wild type. Functions related to these gene networks were consistent with a better cardiac contractility and performance. We conclude that EDNRB plays a key role in hypoxia tolerance and that a lower level of EDNRB contributes, at least in part, to HA adaptation in humans. PMID:26240367

  9. Right ventricular morphology and function in chronic obstructive pulmonary disease patients living at high altitude.

    PubMed

    Güvenç, Tolga Sinan; Erer, Hatice Betül; Kul, Seref; Perinçek, Gökhan; Ilhan, Sami; Sayar, Nurten; Yıldırım, Binnaz Zeynep; Doğan, Coşkun; Karabağ, Yavuz; Balcı, Bahattin; Eren, Mehmet

    2013-01-01

    Pulmonary vasculature is affected in patients with chronic pulmonary obstructive disease (COPD). As a result of increased pulmonary resistance, right ventricular morphology and function are altered in COPD patients. High altitude and related hypoxia causes pulmonary vasoconstriction, thereby affecting the right ventricle. We aimed to investigate the combined effects of COPD and altitude-related chronic hypoxia on right ventricular morphology and function. Forty COPD patients living at high altitude (1768 m) and 41 COPD patients living at sea level were enrolled in the study. All participants were diagnosed as COPD by a pulmonary diseases specialist depending on symptoms, radiologic findings and pulmonary function test results. Detailed two-dimensional echocardiography was performed by a cardiologist at both study locations. Oxygen saturation and mean pulmonary artery pressure were higher in the high altitude group. Right ventricular end diastolic diameter, end systolic diameter, height and end systolic area were significantly higher in the high altitude group compared to the sea level group. Parameters of systolic function, including tricuspid annular systolic excursion, systolic velocity of tricuspid annulus and right ventricular isovolumic acceleration were similar between groups, while fractional area change was significantly higher in the sea level groups compared to the high altitude group. Indices of diastolic function and myocardial performance index were similar between groups. An increase in mean pulmonary artery pressure and right ventricular dimensions are observed in COPD patients living at high altitude. Despite this increase, systolic and diastolic functions of the right ventricle, as well as global right ventricular performance are similar in COPD patients living at high altitude and sea level. Altitude-related adaptation to chronic hypoxia could explain these findings. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic

  10. A strategy for oxygen conditioning at high altitude: comparison with air conditioning.

    PubMed

    West, John B

    2015-09-15

    Large numbers of people live or work at high altitude, and many visit to trek or ski. The inevitable hypoxia impairs physical working capacity, and at higher altitudes there is also cognitive impairment. Twenty years ago oxygen enrichment of room air was introduced to reduce the hypoxia, and this is now used in dormitories, hotels, mines, and telescopes. However, recent advances in technology now allow large amounts of oxygen to be obtained from air or cryogenic oxygen sources. As a result it is now feasible to oxygenate large buildings and even institutions such as hospitals. An analogy can be drawn between air conditioning that has improved the living and working conditions of millions of people who live in hot climates and oxygen conditioning that can do the same at high altitude. Oxygen conditioning is similar to air conditioning except that instead of cooling the air, the oxygen concentration is raised, thus reducing the equivalent altitude. Oxygen conditioning on a large scale could transform living and working conditions at high altitude, where it could be valuable in homes, hospitals, schools, dormitories, company headquarters, banks, and legislative settings. Copyright © 2015 the American Physiological Society.

  11. Pulmonary vascular disease in a rabbit a high altitude

    NASA Astrophysics Data System (ADS)

    Heath, Donald; Williams, David; Rios-Datenz, Jaime; Gosney, John

    1990-03-01

    A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.

  12. Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude

    PubMed Central

    Coppel, Jonny; Court, Jo; van der Kaaij, Jildou; Vercueil, Andre; Feelisch, Martin; Levett, Denny; Mythen, Monty; Grocott, Michael P.; Martin, Daniel

    2017-01-01

    Anecdotal reports suggest that Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, despite exhibiting lower arterial oxygen content than acclimatized lowlanders. This study tested the hypothesis that Sherpas exposed to hypobaric hypoxia on ascent to 5,300 m develop increased microcirculatory blood flow as a means of maintaining tissue oxygen delivery. Incident dark-field imaging was used to obtain images of the sublingual microcirculation from 64 Sherpas and 69 lowlanders. Serial measurements were obtained from participants undertaking an ascent from baseline testing (35 m or 1,300 m) to Everest base camp (5,300 m) and following subsequent descent in Kathmandu (1,300 m). Microcirculatory flow index and heterogeneity index were used to provide indexes of microcirculatory flow, while capillary density was assessed using small vessel density. Sherpas demonstrated significantly greater microcirculatory blood flow at Everest base camp, but not at baseline testing or on return in Kathmandu, than lowlanders. Additionally, blood flow exhibited greater homogeneity at 5,300 and 1,300 m (descent) in Sherpas than lowlanders. Sublingual small vessel density was not different between the two cohorts at baseline testing or at 1,300 m; however, at 5,300 m, capillary density was up to 30% greater in Sherpas. These data suggest that Sherpas can maintain a significantly greater microcirculatory flow per unit time and flow per unit volume of tissue at high altitude than lowlanders. These findings support the notion that peripheral vascular factors at the microcirculatory level may be important in the process of adaptation to hypoxia. NEW & NOTEWORTHY Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, yet the physiological mechanisms underlying this tolerance remain unknown. In our prospective study, conducted on healthy volunteers ascending to Everest base camp (5,300 m), we demonstrated that Sherpas have a higher

  13. Analysis of high-altitude de-acclimatization syndrome after exposure to high altitudes: a cluster-randomized controlled trial.

    PubMed

    He, Binfeng; Wang, Jianchun; Qian, Guisheng; Hu, Mingdong; Qu, Xinming; Wei, Zhenghua; Li, Jin; Chen, Yan; Chen, Huaping; Zhou, Qiquan; Wang, Guansong

    2013-01-01

    The syndrome of high-altitude de-acclimatization commonly takes place after long-term exposure to high altitudes upon return to low altitudes. The syndrome severely affects the returnee's quality of life. However, little attention has been paid to careful characterization of the syndrome and their underlying mechanisms. Male subjects from Chongqing (n = 67, 180 m) and Kunming (n = 70, 1800 m) visited a high-altitude area (3650 m) about 6 months and then returned to low-altitude. After they came back, all subjects were evaluated for high-altitude de-acclimatization syndrome on the 3(rd), 50(th), and 100(th). Symptom scores, routine blood and blood gas tests, and myocardial zymograms assay were used for observation their syndrome. The results showed that the incidence and severity of symptoms had decreased markedly on the 50(th) and 100(th) days, compared with the 3(rd) day. The symptom scores and incidence of different symptoms were lower among subjects returning to Kunming than among those returning to Chongqing. On the 3(rd) day, RBC, Hb, Hct, CK, CK-MB, and LDH values were significantly lower than values recorded at high altitudes, but they were higher than baseline values. On the 50(th) day, these values were not different from baseline values, but LDH levels did not return to baseline until the 100(th) day. These data show that, subjects who suffered high-altitude de-acclimatization syndrome, the recovery fully processes takes a long time (≥ 100(th) days). The appearance of the syndrome is found to be related to the changes in RBC, Hb, Hct, CK, CK-MB, and LDH levels, which should be caused by reoxygenation after hypoxia.

  14. Impact of extreme exercise at high altitude on oxidative stress in humans

    PubMed Central

    Dumke, Charles; Slivka, Dustin; Ruby, Brent

    2015-01-01

    Abstract Exercise and oxidative stress research continues to grow as a physiological subdiscipline. The influence of high altitude on exercise and oxidative stress is among the recent topics of intense study in this area. Early findings indicate that exercise at high altitude has an independent influence on free radical generation and the resultant oxidative stress. This review provides a detailed summary of oxidative stress biochemistry as gleaned mainly from studies of humans exercising at high altitude. Understanding of the human response to exercise at altitude is largely derived from field‐based research at altitudes above 3000 m in addition to laboratory studies which employ normobaric hypoxia. The implications of oxidative stress incurred during high altitude exercise appear to be a transient increase in oxidative damage followed by redox‐sensitive adaptations in multiple tissues. These outcomes are consistent for lowland natives, high altitude acclimated sojourners and highland natives, although the latter group exhibits a more robust adaptive response. To date there is no evidence that altitude‐induced oxidative stress is deleterious to normal training or recovery scenarios. Limited evidence suggests that deleterious outcomes related to oxidative stress are limited to instances where individuals are exposed to extreme elevations for extended durations. However, confirmation of this tentative conclusion requires further investigation. More applicably, altitude‐induced hypoxia may have an independent influence on redox‐sensitive adaptive responses to exercise and exercise recovery. If correct, these findings may hold important implications for athletes, mountaineers, and soldiers working at high altitude. These points are raised within the confines of published research on the topic of oxidative stress during exercise at altitude. PMID:26453842

  15. High altitude cognitive performance and COPD interaction

    PubMed Central

    Kourtidou-Papadeli, C; Papadelis, C; Koutsonikolas, D; Boutzioukas, S; Styliadis, C; Guiba-Tziampiri, O

    2008-01-01

    Introduction: Thousands of people work and perform everyday in high altitude environment, either as pilots, or shift workers, or mountaineers. The problem is that most of the accidents in this environment have been attributed to human error. The objective of this study was to assess complex cognitive performance as it interacts with respiratory insufficiency at altitudes of 8000 feet and identify the potential effect of hypoxia on safe performance. Methods: Twenty subjects participated in the study, divided in two groups: Group I with mild asymptomatic chronic obstructive pulmonary disease (COPD), and Group II with normal respiratory function. Altitude was simulated at 8000 ft. using gas mixtures. Results: Individuals with mild COPD experienced notable hypoxemia with significant performance decrements and increased number of errors at cabin altitude, compared to normal subjects, whereas their blood pressure significantly increased. PMID:19048098

  16. Impaired dynamic cerebral autoregulation at extreme high altitude even after acclimatization.

    PubMed

    Iwasaki, Ken-ichi; Zhang, Rong; Zuckerman, Julie H; Ogawa, Yojiro; Hansen, Lærke H; Levine, Benjamin David

    2011-01-01

    Cerebral blood flow (CBF) increases and dynamic cerebral autoregulation is impaired by acute hypoxia. We hypothesized that progressive hypocapnia with restoration of arterial oxygen content after altitude acclimatization would normalize CBF and dynamic cerebral autoregulation. To test this hypothesis, dynamic cerebral autoregulation was examined by spectral and transfer function analyses between arterial pressure and CBF velocity variabilities in 11 healthy members of the Danish High-Altitude Research Expedition during normoxia and acute hypoxia (10.5% O(2)) at sea level, and after acclimatization (for over 1 month at 5,260 m at Chacaltaya, Bolivia). Arterial pressure and CBF velocity in the middle cerebral artery (transcranial Doppler), were recorded on a beat-by-beat basis. Steady-state CBF velocity increased during acute hypoxia, but normalized after acclimatization with partial restoration of SaO(2) (acute, 78% ± 2%; chronic, 89% ± 1%) and progression of hypocapnia (end-tidal carbon dioxide: acute, 34 ± 2 mm Hg; chronic, 21 ± 1 mm Hg). Coherence (0.40 ± 0.05 Units at normoxia) and transfer function gain (0.77 ± 0.13 cm/s per mm Hg at normoxia) increased, and phase (0.86 ± 0.15 radians at normoxia) decreased significantly in the very-low-frequency range during acute hypoxia (gain, 141% ± 24%; coherence, 136% ± 29%; phase, -25% ± 22%), which persisted after acclimatization (gain, 136% ± 36%; coherence, 131% ± 50%; phase, -42% ± 13%), together indicating impaired dynamic cerebral autoregulation in this frequency range. The similarity between both acute and chronic conditions suggests that dynamic cerebral autoregulation is impaired by hypoxia even after successful acclimatization to an extreme high altitude.

  17. Can patients with coronary heart disease go to high altitude?

    PubMed

    Dehnert, Christoph; Bärtsch, Peter

    2010-01-01

    Tourism to high altitude is very popular and includes elderly people with both manifest and subclinical coronary heart disease (CHD). Thus, risk assessment regarding high altitude exposure of patients with CHD is of increasing interest, and individual recommendations are expected despite the lack of sufficient scientific evidence. The major factor increasing cardiac stress is hypoxia. At rest and for a given external workload, myocardial oxygen demand is increased at altitude, particularly in nonacclimatized individuals, and there is some evidence that blood-flow reserve is reduced in atherosclerotic coronary arteries even in the absence of severe stenosis. Despite a possible imbalance between oxygen demand and oxygen delivery, studies on selected patients have shown that exposure and exercise at altitudes of 3000 to 3500 m is generally safe for patients with stable CHD and sufficient work capacity. During the first days at altitude, patients with stable angina may develop symptoms of myocardial ischemia at slightly lower heart rate x  blood-pressure products. Adverse cardiac events, however, such as unstable angina coronary syndromes, do not occur more frequently compared with sea level except for those who are unaccustomed to exercise. Therefore, training should start before going to altitude, and the altitude-related decrease in exercise capacity should be considered. Travel to 3500 m should be avoided unless patients have stable disease, preserved left ventricular function without residual capacity, and above-normal exercise capacity. CHD patients should avoid travel to elevations above 4500 m owing to severe hypoxia at these altitudes. The risk assessment of CHD patients at altitude should always consider a possible absence of medical support and that cardiovascular events may turn into disaster.

  18. High altitude hypoxia, a mask and a Street. Donation of an aviation BLB oxygen mask apparatus from World War 2.

    PubMed

    Cooper, M G; Street, N E

    2017-03-01

    The history of hypoxia prevention is closely inter-related with high altitude mountain and aviation physiology. One pioneering attempt to overcome low inspired oxygen partial pressures in aviation was the BLB mask-named after the three designers-Walter M Boothby, W Randolph Lovelace II and Arthur H Bulbulian. This mask and its variations originated just prior to World War 2 when aircraft were able to fly higher than 10,000 feet and pilot hypoxia affecting performance was an increasing problem. We give a brief description of the mask and its designers and discuss the donation of a model used by the British War Office in October 1940 and donated to the Harry Daly Museum at the Australian Society of Anaesthetists by the family of Dr Fred Street. Dr Street was a pioneering paediatric surgeon in Australia and served as a doctor in the Middle East and New Guinea in World War 2. He received the Military Cross.

  19. Sustained sympathetic activity in altitude acclimatizing lowlanders and high-altitude natives.

    PubMed

    Lundby, C; Calbet, J; van Hall, G; Saltin, B; Sander, M

    2018-03-01

    Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute chemoreflex-mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O 2 ) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high-altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude-induced sympathetic activity, which is sustained in well-acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Elevated Suicide Rates at High Altitude: Sociodemographic and Health Issues May Be to Blame

    ERIC Educational Resources Information Center

    Betz, Marian E.; Valley, Morgan A.; Lowenstein, Steven R.; Hedegaard, Holly; Thomas, Deborah; Stallones, Lorann; Honigman, Benjamin

    2011-01-01

    Suicide rates are higher at high altitudes; some hypothesize that hypoxia is the cause. We examined 8,871 suicides recorded in 2006 in 15 states by the National Violent Death Reporting System, with the victim's home county altitude determined from the National Elevation Dataset through FIPS code matching. We grouped cases by altitude (low less…

  1. High-Altitude-Induced alterations in Gut-Immune Axis: A review.

    PubMed

    Khanna, Kunjan; Mishra, K P; Ganju, Lilly; Kumar, Bhuvnesh; Singh, Shashi Bala

    2018-03-04

    High-altitude sojourn above 8000 ft is increasing day by day either for pilgrimage, mountaineering, holidaying or for strategic reasons. In India, soldiers are deployed to these high mountains for their duty or pilgrims visit to the holy places, which are located at very high altitude. A large population also resides permanently in high altitude regions. Every year thousands of pilgrims visit Holy cave of Shri Amarnath ji, which is above 15 000 ft. The poor acclimatization to high altitude may cause alteration in immunity. The low oxygen partial pressure may cause alterations in gut microbiota, which may cause changes in gut immunity. Effect of high altitude on gut-associated mucosal system is new area of research. Many studies have been carried out to understand the physiology and immunology behind the high-altitude-induced gut problems. Few interventions have also been discovered to circumvent the problems caused due to high-altitude conditions. In this review, we have discussed the effects of high-altitude-induced changes in gut immunity particularly peyer's patches, NK cells and inflammatory cytokines, secretary immunoglobulins and gut microbiota. The published articles from PubMed and Google scholar from year 1975 to 2017 on high-altitude hypoxia and gut immunity are cited in this review.

  2. Analysis of High-Altitude De-Acclimatization Syndrome after Exposure to High Altitudes: A Cluster-Randomized Controlled Trial

    PubMed Central

    Hu, Mingdong; Qu, Xinming; Wei, Zhenghua; Li, Jin; Chen, Yan; Chen, Huaping; Zhou, Qiquan; Wang, Guansong

    2013-01-01

    The syndrome of high-altitude de-acclimatization commonly takes place after long-term exposure to high altitudes upon return to low altitudes. The syndrome severely affects the returnee's quality of life. However, little attention has been paid to careful characterization of the syndrome and their underlying mechanisms. Male subjects from Chongqing (n = 67, 180 m) and Kunming (n = 70, 1800 m) visited a high-altitude area (3650 m) about 6 months and then returned to low-altitude. After they came back, all subjects were evaluated for high-altitude de-acclimatization syndrome on the 3rd, 50th, and 100th. Symptom scores, routine blood and blood gas tests, and myocardial zymograms assay were used for observation their syndrome. The results showed that the incidence and severity of symptoms had decreased markedly on the 50th and 100th days, compared with the 3rd day. The symptom scores and incidence of different symptoms were lower among subjects returning to Kunming than among those returning to Chongqing. On the 3rd day, RBC, Hb, Hct, CK, CK-MB, and LDH values were significantly lower than values recorded at high altitudes, but they were higher than baseline values. On the 50th day, these values were not different from baseline values, but LDH levels did not return to baseline until the 100th day. These data show that, subjects who suffered high-altitude de-acclimatization syndrome, the recovery fully processes takes a long time (≥100th days). The appearance of the syndrome is found to be related to the changes in RBC, Hb, Hct, CK, CK-MB, and LDH levels, which should be caused by reoxygenation after hypoxia. PMID:23650508

  3. High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment

    PubMed Central

    Taylor, Andrew T.

    2011-01-01

    High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler. PMID:23908794

  4. Exposure to Hypoxia at High Altitude (5380 m) for 1 Year Induces Reversible Effects on Semen Quality and Serum Reproductive Hormone Levels in Young Male Adults.

    PubMed

    He, Jiang; Cui, Jianhua; Wang, Rui; Gao, Liang; Gao, Xiaokang; Yang, Liu; Zhang, Qiong; Cao, Jinjun; Yu, Wuzhong

    2015-09-01

    This study investigated the effect of hypoxia at high altitude on the semen quality and the serum reproductive hormone levels in male adults. A total of 52 male soldiers were enrolled in this cohort study. They were exposed to hypoxia at high altitude (5380 m) for 12 months when undergoing a service. After exposure, they were followed up for 6 months. The samples of semen and peripheral blood were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12 months of exposure (M12), and 6 months after exposure (M18). The semen quality was assessed with computer-assisted analysis system, and the serum levels of reproductive hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA. Compared with those at M0, total sperm count, sperm density, motility, survival rate, and serum levels of LH, PRL and testosterone were significantly decreased, whereas the liquefaction time was significantly prolonged and serum FSH level was significantly increased at M6 (p<0.05). At M12, total sperm count and sperm density increased, whereas sperm motility, survival rate, and the liquefaction time further decreased. Sperm velocities, progression ratios, and lateral head displacements were also decreased. Serum FSH level decreased while serum LH, PRL, and testosterone levels increased. Compared with those at M6, the changes in these detected parameters of semen and hormone at M12 were significant (p<0.05). At M18, all these detected parameters except testosterone level returned to levels comparable to those before exposure. In conclusion, hypoxia at high altitude causes adverse effects on semen quality and reproductive hormones, and these effects are reversible.

  5. Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders

    PubMed Central

    Holm, Lars; Haslund, Mads Lyhne; Robach, Paul; van Hall, Gerrit; Calbet, Jose A. L.; Saltin, Bengt; Lundby, Carsten

    2010-01-01

    As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often reported. The underlying mechanism has been suggested to involve a decrease in protein synthesis in order to conserve O2. With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-13C-leucine in nine healthy male subjects at sea level and subsequently at high-altitude (4559 m) after 7–9 days of acclimatization. Physical activity levels and food and energy intake were controlled prior to the two experimental conditions with the aim to standardize these confounding factors. Blood samples and expired breath samples were collected hourly during the 4 hour trial and vastus lateralis muscle biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted state. Myofibrillar protein synthesis rate was doubled; 0.041±0.018 at sea-level to 0.080±0.018%⋅hr−1 (p<0.05) when acclimatized to high altitude. The sarcoplasmic protein synthesis rate was in contrast unaffected by altitude exposure; 0.052±0.019 at sea-level to 0.059±0.010%⋅hr−1 (p>0.05). Trends to increments in whole body protein kinetics were seen: Degradation rate elevated from 2.51±0.21 at sea level to 2.73±0.13 µmol⋅kg−1⋅min−1 (p = 0.05) at high altitude and synthesis rate similar; 2.24±0.20 at sea level and 2.43±0.13 µmol⋅kg−1⋅min−1 (p>0.05) at altitude. We conclude that whole body amino acid flux is increased due to an elevated protein turnover rate. Resting skeletal muscle myocontractile protein synthesis rate was concomitantly elevated by high-altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was unaffected by hypoxia. These changed responses may lead to divergent adaptation over the course of prolonged exposure. PMID:21187972

  6. Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-Dose Ultraviolet Radiation in High-Altitude Environments

    PubMed Central

    Zhang, Qian; Gou, Wenyu; Wang, Xiaotong; Zhang, Yawen; Ma, Jun; Zhang, Hongliang; Zhang, Ying; Zhang, Hao

    2016-01-01

    Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of nonsynonymous single nucleotide polymorphisms between highland and lowland populations was analyzed using chi-square test, which showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development and adaptations to hypoxia and intense radiation. RNA sequencing revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Several candidate genes involved in the development of cardiorespiratory system (FGFR1, CTGF, ADAM9, JPH2, SATB1, BMP4, LOX, LPR, ANGPTL4, and HYAL1), inflammation and immune responses (AIRE, MYO1F, ZAP70, DDX60, CCL19, CD47, JSC, and FAS), DNA repair, and responses to radiation (VCP, ASH2L, and FANCG) were identified to play key roles in the adaptation to high-altitude conditions. Our data provide new insights into the unique adaptations of highland animals to extreme environments. PMID:26907498

  7. Impaired dynamic cerebral autoregulation at extreme high altitude even after acclimatization

    PubMed Central

    Iwasaki, Ken-ichi; Zhang, Rong; Zuckerman, Julie H; Ogawa, Yojiro; Hansen, Lærke H; Levine, Benjamin David

    2011-01-01

    Cerebral blood flow (CBF) increases and dynamic cerebral autoregulation is impaired by acute hypoxia. We hypothesized that progressive hypocapnia with restoration of arterial oxygen content after altitude acclimatization would normalize CBF and dynamic cerebral autoregulation. To test this hypothesis, dynamic cerebral autoregulation was examined by spectral and transfer function analyses between arterial pressure and CBF velocity variabilities in 11 healthy members of the Danish High-Altitude Research Expedition during normoxia and acute hypoxia (10.5% O2) at sea level, and after acclimatization (for over 1 month at 5,260 m at Chacaltaya, Bolivia). Arterial pressure and CBF velocity in the middle cerebral artery (transcranial Doppler), were recorded on a beat-by-beat basis. Steady-state CBF velocity increased during acute hypoxia, but normalized after acclimatization with partial restoration of SaO2 (acute, 78%±2% chronic, 89%±1%) and progression of hypocapnia (end-tidal carbon dioxide: acute, 34±2 mm Hg; chronic, 21±1 mm Hg). Coherence (0.40±0.05 Units at normoxia) and transfer function gain (0.77±0.13 cm/s per mm Hg at normoxia) increased, and phase (0.86±0.15 radians at normoxia) decreased significantly in the very-low-frequency range during acute hypoxia (gain, 141%±24% coherence, 136%±29% phase, −25%±22%), which persisted after acclimatization (gain, 136%±36% coherence, 131%±50% phase, −42%±13%), together indicating impaired dynamic cerebral autoregulation in this frequency range. The similarity between both acute and chronic conditions suggests that dynamic cerebral autoregulation is impaired by hypoxia even after successful acclimatization to an extreme high altitude. PMID:20571521

  8. Nasal variation in relation to high-altitude adaptations among Tibetans and Andeans.

    PubMed

    Butaric, Lauren N; Klocke, Ross P

    2018-05-01

    High-altitude (>2500 m) populations face several pressures, including hypoxia and cold-dry air, resulting in greater respiratory demand to obtain more oxygen and condition inspired air. While cardiovascular and pulmonary adaptations to high-altitude hypoxia have been extensively studied, adaptations of upper-respiratory structures, e.g., nasal cavity, remain untested. This study investigates whether nasal morphology presents adaptations to hypoxic (larger noses) and/or cold-dry (tall/narrow noses) conditions among high-altitude samples. CT scans of two high- and four low-altitude samples from diverse climates were collected (n = 130): high-altitude Tibetans and Peruvians; low-altitude Peruvians, Southern Chinese (temperate), Mongolian-Buriats (cold-dry), and Southeast Asians (hot-wet). Facial and nasal distances were calculated from 3D landmarks placed on digitally-modeled crania. Temperature, precipitation, and barometric pressure data were also obtained. Principal components analysis and analyses of variance primarily indicate size-related differences among the cold-dry (Mongolian-Buriats) and hot-wet (Southeast Asians) adapted groups. Two-block partial least squares (PLS) analysis show weak relationships between size-standardized nasal dimensions and environmental variables. However, among PLS1 (85.90% of covariance), Tibetans display relatively larger nasal cavities related to lower temperatures and barometric pressure; regression analyses also indicate high-altitude Tibetans possess relatively larger internal nasal breadths and heights for their facial size. Overall, nasal differences relate to climate among the cold-dry and hot-wet groups. Specific nasal adaptations were not identified among either Peruvian group, perhaps due to their relatively recent migration history and population structure. However, high-altitude Tibetans seem to exhibit a compromise in nasal morphology, serving in increased oxygen uptake, and air-conditioning processes. © 2018

  9. High-altitude haematology: Quechua-Aymara comparisons.

    PubMed

    Arnaud, J; Quilici, J C; Rivière, G

    1981-01-01

    Haematological studies have been carried out at various altitudes between 450 m and 4800 m, on two separate human groups (Quechuas and Aymaras) living in South America. Changes in the haematological parameters do not develop linearly in relation to the attitude. Th impact of chronic hypoxia on erythropoiesis is greater above 3000 m. The haemogram varies quantitatively and not qualitatively (mean corpuscular volume and mean haemoglobin concentration remain constant). The haematological study also reveals the greater adaptability to high altitude of the Aymaras, an adaptability characterized by an increase in red cell count and concentration and a decrease in red cell volume. The adaptative phenomena observed in the Quechuas are reversible, whereas they persist in the Aymaras when they migrate to the lowlands (450 m).

  10. [Effects of simulated hypoxia on dielectric properties of mouse erythrocytes].

    PubMed

    Ma, Qing; Tang, Zhi-Yuan; Wang, Qin-Wen; Zhao, Xin

    2008-02-01

    To explore the influence of simulated altitude hypoxia on dielectric properties of mouse erythrocytes. Experimental animals were divided into the plain control group(control) and simulated altitude hypoxia group (altitude). The AC impedance of mouse erythrocytes was measured with the Agilent 4294A impedance analyzer, the influence of simulated altitude hypoxia on dielectric properties of mouse erythrocytes was observed by cell dielectric spectroscopy, Cole-Cole plots, loss factor spectrum, loss tangent spectrum, and curve fitting analysis of Cole-Cole equation. After mice were exposed to hypoxia at simulated 5000 m altitude for 4 weeks, permittivity at low frequency (epsilonl) and dielectric increment (deltaepsilon) increased 57% and 59% than that of control group respectively, conductivity at low frequency (kappal) and conductivity at high frequency (kappah) reduced 49% and 11% than that of control group respectively. The simulated altitude hypoxia could arise to increase dielectric capability and depress conductive performance on mouse erythrocytes.

  11. Genome-Wide Expression Analysis Suggests Hypoxia-Triggered Hyper-Coagulation Leading to Venous Thrombosis at High Altitude.

    PubMed

    Jha, Prabhash Kumar; Sahu, Anita; Prabhakar, Amit; Tyagi, Tarun; Chatterjee, Tathagata; Arvind, Prathima; Nair, Jiny; Gupta, Neha; Kumari, Babita; Nair, Velu; Bajaj, Nitin; Shanker, Jayashree; Sharma, Manish; Kumar, Bhuvnesh; Ashraf, Mohammad Zahid

    2018-06-04

    Venous thromboembolism (VTE), a multi-factorial disease, is the third most common cardiovascular disease. Established genetic and acquired risk factors are responsible for the onset of VTE. High altitude (HA) also poses as an additional risk factor, predisposing individuals to VTE; however, its molecular mechanism remains elusive. This study aimed to identify genes/pathways associated with the pathophysiology of deep vein thrombosis (DVT) at HA. Gene expression profiling of DVT patients, who developed the disease, either at sea level or at HA-DVT locations, resulted in differential expression of 378 and 875 genes, respectively. Gene expression profiles were subjected to bioinformatic analysis, followed by technical and biological validation of selected genes using quantitative reverse transcription-polymerase chain reaction. Both gene ontology and pathway analysis showed enrichment of genes involved in haemostasis and platelet activation in HA-DVT patients with the most relevant pathway being 'response to hypoxia'. Thus, given the environmental condition the differential expression of hypoxia-responsive genes (angiogenin, ribonuclease, RNase A family, 5; early growth response 1; lamin A; matrix metallopeptidase 14 [membrane-inserted]; neurofibromin 1; PDZ and LIM domain 1; procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1; solute carrier family 6 [neurotransmitter transporter, serotonin], member 4; solute carrier family 9 [sodium/hydrogen exchanger], member 1; and TEK tyrosine kinase, endothelial) in HA-DVT could be a determining factor to understand the pathophysiology of DVT at HA. Schattauer GmbH Stuttgart.

  12. The Genetic Architecture of Adaptations to High Altitude in Ethiopia

    PubMed Central

    Alkorta-Aranburu, Gorka; Beall, Cynthia M.; Witonsky, David B.; Gebremedhin, Amha; Pritchard, Jonathan K.; Di Rienzo, Anna

    2012-01-01

    Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo. PMID:23236293

  13. Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-Dose Ultraviolet Radiation in High-Altitude Environments.

    PubMed

    Zhang, Qian; Gou, Wenyu; Wang, Xiaotong; Zhang, Yawen; Ma, Jun; Zhang, Hongliang; Zhang, Ying; Zhang, Hao

    2016-02-23

    Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of nonsynonymous single nucleotide polymorphisms between highland and lowland populations was analyzed using chi-square test, which showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development and adaptations to hypoxia and intense radiation. RNA sequencing revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Several candidate genes involved in the development of cardiorespiratory system (FGFR1, CTGF, ADAM9, JPH2, SATB1, BMP4, LOX, LPR, ANGPTL4, and HYAL1), inflammation and immune responses (AIRE, MYO1F, ZAP70, DDX60, CCL19, CD47, JSC, and FAS), DNA repair, and responses to radiation (VCP, ASH2L, and FANCG) were identified to play key roles in the adaptation to high-altitude conditions. Our data provide new insights into the unique adaptations of highland animals to extreme environments. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Seven Passive 1-h Hypoxia Exposures Do Not Prevent AMS in Susceptible Individuals.

    PubMed

    Faulhaber, Martin; Pocecco, Elena; Gatterer, Hannes; Niedermeier, Martin; Huth, Maike; Dünnwald, Tobias; Menz, Verena; Bernardi, Luciano; Burtscher, Martin

    2016-12-01

    The present study evaluated the effects of a preacclimatization program comprising seven passive 1-h exposures to 4500-m normobaric hypoxia on the prevalence and severity of acute mountain sickness (AMS) during a subsequent exposure to real high altitude in persons susceptible to AMS. The project was designed as a randomized controlled trial including 32 healthy female and male participants with known susceptibility to AMS symptoms. After baseline measurements, participants were randomly assigned to the hypoxia or the control group to receive the preacclimatization program (seven passive 1-h exposures within 7 d to normobaric hypoxia or sham hypoxia). After completing preacclimatization, participants were transported (bus, cog railway) to real high altitude (3650 m, Mönchsjoch Hut, Switzerland) and stayed there for 45 h (two nights). Symptoms of AMS and physiological responses were determined repeatedly. AMS incidence and severity did not significantly differ between groups during the high-altitude exposure. In total, 59% of the hypoxia and 67% of the control group suffered from AMS at one or more time points during the high-altitude exposure. Hypoxic and hypercapnic ventilatory responses were not affected by the preacclimatization program. Resting ventilation at high altitude tended to be higher (P = 0.06) in the hypoxia group compared with the control group. No significant between-group differences were detected for heart rate variability, arterial oxygen saturation, and hematological and ventilatory parameters during the high-altitude exposure. Preacclimatization using seven passive 1-h exposures to normobaric hypoxia corresponding to 4500 m did not prevent AMS development during a subsequent high-altitude exposure in AMS-susceptible persons.

  15. Serum irisin and myostatin levels after 2 weeks of high-altitude climbing.

    PubMed

    Śliwicka, Ewa; Cisoń, Tomasz; Kasprzak, Zbigniew; Nowak, Alicja; Pilaczyńska-Szcześniak, Łucja

    2017-01-01

    Exposure to high-altitude hypoxia causes physiological and metabolic adaptive changes by disturbing homeostasis. Hypoxia-related changes in skeletal muscle affect the closely interconnected energy and regeneration processes. The balance between protein synthesis and degradation in the skeletal muscle is regulated by several molecules such as myostatin, cytokines, vitamin D, and irisin. This study investigates changes in irisin and myostatin levels in male climbers after a 2-week high-altitude expedition, and their association with 25(OH)D and indices of inflammatory processes. The study was performed in 8 men aged between 23 and 31 years, who participated in a 2-week climbing expedition in the Alps. The measurements of body composition and serum concentrations of irisin, myostatin, 25(OH)D, interleukin-6, myoglobin, high-sensitivity C-reactive protein, osteoprotegerin, and high-sensitivity soluble receptor activator of NF-κB ligand (sRANKL) were performed before and after expedition. A 2-week exposure to hypobaric hypoxia caused significant decrease in body mass, body mass index (BMI), free fat mass and irisin, 25-Hydroxyvitamin D levels. On the other hand, significant increase in the levels of myoglobin, high-sensitivity C-reactive protein, interleukin-6, and osteoprotegerin were noted. The observed correlations of irisin with 25(OH)D levels, as well as myostatin levels with inflammatory markers and the OPG/RANKL ratio indicate that these myokines may be involved in the energy-related processes and skeletal muscle regeneration in response to 2-week exposure to hypobaric hypoxia.

  16. Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

    PubMed Central

    Hebbel, R P; Eaton, J W; Kronenberg, R S; Zanjani, E D; Moore, L G; Berger, E M

    1978-01-01

    To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude. PMID:29054

  17. The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives

    PubMed Central

    van Hall, G; Lundby, C; Araoz, M; Calbet, J A L; Sander, M; Saltin, B

    2009-01-01

    Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high-altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22–31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26–37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea-level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High-altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown. PMID:19139048

  18. Pulmonary vascular remodelling in a high-altitude Aymara Indian

    NASA Astrophysics Data System (ADS)

    Heath, Donald; Williams, David

    1991-12-01

    A histological study of the pulmonary vasculature in a young male high-altitude Aymara Indian revealed four aspects of interest. There was muscularization of the terminal portion of the pulmonary arterial tree to involve pulmonary arterioles as small as 15 μm in diameter, thus forming a basis for the slightly increased pulmonary vascular resistance of native highlanders. Intimal longitudinal muscle was found in pulmonary arteries and arterioles and thought to be due to chronic alveolar hypoxia. Inner muscular tubes similar to those found in chronic obstructive lung disease were present. Pulmonary veins and venules also showed intimal muscularization suggesting that alveolar hypoxia affects vascular smooth muscle cells per se irrespective of their situation. The nature of the remodelling in a pulmonary blood vessel depends on a combination of hypoxia and haemodynamics.

  19. Insulin secretion at high altitude in man

    NASA Astrophysics Data System (ADS)

    Sawhney, R. C.; Malhotra, A. S.; Singh, T.; Rai, R. M.; Sinha, K. C.

    1986-09-01

    The effect of hypoxia on circulatory levels of insulin, its response to oral glucose administration (100 g) and changes in circadian rhythms of glucose as well as insulin were evaluated in euglycemic males at sea level (SL, 220 m) during their stay at high altitude (3500 m, SJ) and in high altitude natives (HAN). Basal glucose levels were not altered at high altitude but the rise in glucose (δ glucose) after glucose load was significantly higher in SJ and HAN (p<0.01) as compared to SL values. An increase (p<0.01) both in basal as well as glucose induced rise in insulin secretion (δ insulin) was observed at HA. The rise in insulin in SJ was significantly higher (p<0.01) than in HAN. This elevation in glucose and insulin levels was also evident at different times of the day. The circadian rhythmicity of glucose as well as insulin was altered by the altitude stress. The findings of the study show a rise in insulin level at HA but the hyperglycemia in the face of hyper-insulinism require the presumption of a simultaneous and dispropotionate rise of insulin antagonistic hormones upsetting the effect of insulin on glucose metabolism.

  20. Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

    PubMed

    Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

    2005-07-01

    Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

  1. The Andean Adaptive Toolkit to Counteract High Altitude Maladaptation: Genome-Wide and Phenotypic Analysis of the Collas

    PubMed Central

    Eichstaedt, Christina A.; Antão, Tiago; Pagani, Luca; Cardona, Alexia; Kivisild, Toomas; Mormina, Maru

    2014-01-01

    During their migrations out of Africa, humans successfully colonised and adapted to a wide range of habitats, including extreme high altitude environments, where reduced atmospheric oxygen (hypoxia) imposes a number of physiological challenges. This study evaluates genetic and phenotypic variation in the Colla population living in the Argentinean Andes above 3500 m and compares it to the nearby lowland Wichí group in an attempt to pinpoint evolutionary mechanisms underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25 individuals from each population. In genome-wide scans of extended haplotype homozygosity Collas showed the strongest signal around VEGFB, which plays an essential role in the ischemic heart, and ELTD1, another gene crucial for heart development and prevention of cardiac hypertrophy. Moreover, pathway enrichment analysis showed an overrepresentation of pathways associated with cardiac morphology. Taken together, these findings suggest that Colla highlanders may have evolved a toolkit of adaptative mechanisms resulting in cardiac reinforcement, most likely to counteract the adverse effects of the permanently increased haematocrit and associated shear forces that characterise the Andean response to hypoxia. Regulation of cerebral vascular flow also appears to be part of the adaptive response in Collas. These findings are not only relevant to understand the evolution of hypoxia protection in high altitude populations but may also suggest new avenues for medical research into conditions where hypoxia constitutes a detrimental factor. PMID:24686296

  2. Is hypoxia training good for muscles and exercise performance?

    PubMed

    Vogt, Michael; Hoppeler, Hans

    2010-01-01

    Altitude training has become very popular among athletes as a means to further increase exercise performance at sea level or to acclimatize to competition at altitude. Several approaches have evolved during the last few decades, with "live high-train low" and "live low-train high" being the most popular. This review focuses on functional, muscular, and practical aspects derived from extensive research on the "live low-train high" approach. According to this, subjects train in hypoxia but remain under normoxia for the rest of the time. It has been reasoned that exercising in hypoxia could increase the training stimulus. Hypoxia training studies published in the past have varied considerably in altitude (2300-5700 m) and training duration (10 days to 8 weeks) and the fitness of the subjects. The evidence from muscle structural, biochemical, and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available performance capacity data such as maximal oxygen uptake (Vo(2)max) and (maximal) power output, hypoxia as a supplement to training is not consistently found to be advantageous for performance at sea level. Stronger evidence exists for benefits of hypoxic training on performance at altitude. "Live low-train high" may thus be considered when altitude acclimatization is not an option. In addition, the complex pattern of gene expression adaptations induced by supplemental training in hypoxia, but not normoxia, suggest that muscle tissue specifically responds to hypoxia. Whether and to what degree these gene expression changes translate into significant changes in protein concentrations that are ultimately responsible for observable structural or functional phenotypes remains open. It is conceivable that the global functional markers such as Vo(2)max and (maximal) power output are too coarse to detect more subtle changes that might still be functionally relevant, at least to high-level athletes.

  3. The Use of Dexamethasone in Support of High-Altitude Ground Operations and Physical Performance: Review of the Literature

    DTIC Science & Technology

    2014-12-01

    rates vary dramatically, the physiological effect of hypobaric high-altitude hypoxia ( HHH ) is ubiquitous.1,2 Symptoms of less severe cases of HHH ...nausea, headache, and peripheral edema.3-6 More severe cases of HHH may result in acute mountain sickness (AMS), high-altitude pulmonary edema

  4. Stunting and the Prediction of Lung Volumes Among Tibetan Children and Adolescents at High Altitude.

    PubMed

    Weitz, Charles A; Garruto, Ralph M

    2015-12-01

    This study examines the extent to which stunting (height-for-age Z-scores ≤ -2) compromises the use of low altitude prediction equations to gauge the general increase in lung volumes during growth among high altitude populations. The forced vital capacity (FVC) and forced expiratory volume (FEV1) of 208 stunted and 365 non-stunted high-altitude Tibetan children and adolescents between the ages of 6 and 20 years are predicted using the Third National Health and Nutrition Examination Survey (NHANESIII) and the Global Lung Function Initiative (GLF) equations, and compared to observed lung volumes. Stunted Tibetan children show smaller positive deviations from both NHANESIII and GLF prediction equations at most ages than non-stunted children. Deviations from predictions do not correspond to differences in body proportions (sitting heights and chest circumferences relative to stature) between stunted and non-stunted children; but appear compatible with the effects of retarded growth and lung maturation that are likely to exist among stunted children. These results indicate that, before low altitude standards can be used to evaluate the effects of hypoxia, or before high altitude populations can be compared to any other group, it is necessary to assess the relative proportion of stunted children in the samples. If the proportion of stunted children in a high altitude population differs significantly from the proportion in the comparison group, lung function comparisons are unlikely to yield an accurate assessment of the hypoxia effect. The best solution to this problem is to (1) use stature and lung function standards based on the same low altitude population; and (2) assess the hypoxic effect by comparing observed and predicted values among high altitude children whose statures are most like those of children on whom the low altitude spirometric standard is based-preferably high altitude children with HAZ-scores ≥ -1.

  5. Comparison of live high: train low altitude and intermittent hypoxic exposure.

    PubMed

    Humberstone-Gough, Clare E; Saunders, Philo U; Bonetti, Darrell L; Stephens, Shaun; Bullock, Nicola; Anson, Judith M; Gore, Christopher J

    2013-01-01

    Live High:Train Low (LHTL) altitude training is a popular ergogenic aid amongst athletes. An alternative hypoxia protocol, acute (60-90 min daily) Intermittent Hypoxic Exposure (IHE), has shown potential for improving athletic performance. The aim of this study was to compare directly the effects of LHTL and IHE on the running and blood characteristics of elite triathletes. Changes in total haemoglobin mass (Hbmass), maximal oxygen consumption (VO2max), velocity at VO2max (vVO2max), time to exhaustion (TTE), running economy, maximal blood lactate concentration ([La]) and 3 mM [La] running speed were compared following 17 days of LHTL (240 h of hypoxia), IHE (10.2 h of hypoxia) or Placebo treatment in 24 Australian National Team triathletes (7 female, 17 male). There was a clear 3.2 ± 4.8% (mean ± 90% confidence limits) increase in Hbmass following LHTL compared with Placebo, whereas the corresponding change of -1.4 ± 4.5% in IHE was unclear. Following LHTL, running economy was 2.8 ± 4.4% improved compared to IHE and 3mM [La] running speed was 4.4 ± 4.5% improved compared to Placebo. After IHE, there were no beneficial changes in running economy or 3mM [La] running speed compared to Placebo. There were no clear changes in VO2max, vVO2max and TTE following either method of hypoxia. The clear difference in Hbmass response between LHTL and IHE indicated that the dose of hypoxia in IHE was insufficient to induce accelerated erythropoiesis. Improved running economy and 3mM [La] running speed following LHTL suggested that this method of hypoxic exposure may enhance performance at submaximal running speeds. Overall, there was no evidence to support the use of IHE in elite triathletes. Key PointsDespite a clear 3.2% increase in haemoglobin mass following 17 days of Live High: Train Low altitude training, no change in maximal aerobic capacity was observed.There were positive changes in running economy and the lactate-speed relationship at submaximal running speeds

  6. Stunting and the Prediction of Lung Volumes Among Tibetan Children and Adolescents at High Altitude

    PubMed Central

    Garruto, Ralph M.

    2015-01-01

    Abstract Weitz, Charles A., and Ralph M. Garruto. Stunting and the prediction of lung volumes among Tibetan children and adolescents at high altitude. High Alt Biol Med 16:306–317, 2015.—This study examines the extent to which stunting (height-for-age Z-scores ≤ −2) compromises the use of low altitude prediction equations to gauge the general increase in lung volumes during growth among high altitude populations. The forced vital capacity (FVC) and forced expiratory volume (FEV1) of 208 stunted and 365 non-stunted high-altitude Tibetan children and adolescents between the ages of 6 and 20 years are predicted using the Third National Health and Nutrition Examination Survey (NHANESIII) and the Global Lung Function Initiative (GLF) equations, and compared to observed lung volumes. Stunted Tibetan children show smaller positive deviations from both NHANESIII and GLF prediction equations at most ages than non-stunted children. Deviations from predictions do not correspond to differences in body proportions (sitting heights and chest circumferences relative to stature) between stunted and non-stunted children; but appear compatible with the effects of retarded growth and lung maturation that are likely to exist among stunted children. These results indicate that, before low altitude standards can be used to evaluate the effects of hypoxia, or before high altitude populations can be compared to any other group, it is necessary to assess the relative proportion of stunted children in the samples. If the proportion of stunted children in a high altitude population differs significantly from the proportion in the comparison group, lung function comparisons are unlikely to yield an accurate assessment of the hypoxia effect. The best solution to this problem is to (1) use stature and lung function standards based on the same low altitude population; and (2) assess the hypoxic effect by comparing observed and predicted values among high altitude children whose

  7. Short-term responses of the kidney to high altitude in mountain climbers

    PubMed Central

    Goldfarb-Rumyantzev, Alexander S.; Alper, Seth L.

    2014-01-01

    In high-altitude climbers, the kidneys play a crucial role in acclimatization and in mountain sickness syndromes [acute mountain sickness (AMS), high-altitude cerebral edema, high-altitude pulmonary edema] through their roles in regulating body fluids, electrolyte and acid–base homeostasis. Here, we discuss renal responses to several high-altitude-related stresses, including changes in systemic volume status, renal plasma flow and clearance, and altered acid–base and electrolyte status. Volume regulation is considered central both to high-altitude adaptation and to maladaptive development of mountain sickness. The rapid and powerful diuretic response to the hypobaric hypoxic stimulus of altitude integrates decreased circulating concentrations of antidiuretic hormone, renin and aldosterone, increased levels of natriuretic hormones, plasma and urinary epinephrine, norepinephrine, endothelin and urinary adrenomedullin, with increased insensible fluid losses and reduced fluid intake. The ventilatory and hormonal responses to hypoxia may predict susceptibility to AMS, also likely influenced by multiple genetic factors. The timing of altitude increases and adaptation also modifies the body's physiologic responses to altitude. While hypovolemia develops as part of the diuretic response to altitude, coincident vascular leak and extravascular fluid accumulation lead to syndromes of high-altitude sickness. Pharmacological interventions, such as diuretics, calcium blockers, steroids, phosphodiesterase inhibitors and β-agonists, may potentially be helpful in preventing or attenuating these syndromes. PMID:23525530

  8. High altitude memory impairment is due to neuronal apoptosis in hippocampus, cortex and striatum.

    PubMed

    Maiti, Panchanan; Singh, Shashi B; Mallick, Birendranath; Muthuraju, Sangu; Ilavazhagan, Govindasami

    2008-12-01

    Cognitive and neuropsychological functions have been impaired at high altitude and the effects depend on altitude and duration of stay. However, the neurobiological mechanism of this impairment is poorly understood especially exposure to different duration. Aim of the present study was to investigate the changes of behavior, biochemistry and morphology after exposure to different duration of hypobaric hypoxia. The rats were exposed continuously to a simulated high altitude of 6100m for 3, 7, 14 and 21 days in an animal decompression chamber. Spatial reference memory was tested by Morris water maze. The oxidative stress markers like free radicals, NO, lipid peroxidation, LDH activity and antioxidant systems like GSH, GSSG, GPx, GR, SOD were estimated from cortex, hippocampus and striatum. The morphological changes, neurodegeneration, DNA fragmentation and mode of cell death have also been studied. It was observed that the spatial reference memory was significantly affected after exposure to hypobaric hypoxia. Increased oxidative stress markers along with decreased effectiveness of antioxidant system were also observed in hypoxia-exposed animals. Further pyknotic, shrunken, tangle-like neurons were observed in all these regions after hypoxia and neurodegeneration, DNA fragmentation and apoptosis were also observed in all the three regions. But after 21 days of exposure, the spatial memory was improved along with improvement of antioxidant activities. Our result suggests that the apoptotic death may be involved in HA-induced memory impairment and after 7 days of exposure the effect was more pronounced but after 21 days of exposure recovery was observed.

  9. ZFP580, a Novel Zinc-Finger Transcription Factor, Is Involved in Cardioprotection of Intermittent High-Altitude Hypoxia against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Zhang, Wen-cheng; Wang, Tian-hui; Mai, Xia; Liu, Hong-tao; Xu, Rui-cheng

    2014-01-01

    Background ZFP580 is a novel C2H2 type zinc-finger transcription factor recently identified by our laboratory. We previously showed that ZFP580 may be involved in cell survival and growth. The aim of this study was to elucidate whether ZFP580 is involved in the cardioprotective effects of intermittent high-altitude (IHA) hypoxia against myocardial ischemia-reperfusion (I/R) injury. Methods and Results After rats were subjected to myocardial ischemia for 30 min followed by reperfusion, ZFP580 expression in the left ventricle was measured. ZFP580 protein expression was found to be up-regulated within 1 h and decreased at 2 h after reperfusion. Comparing normoxic and IHA hypoxia-adapted rats (5000 m, 6 h day−1, 6 weeks) following I/R injury (30 min ischemia and 2 h reperfusion), we found that adaptation to IHA hypoxia attenuated infarct size and plasma leakage of lactate dehydrogenase and creatine kinase-MB. In addition, ZFP580 expression in the myocardium was up-regulated by IHA hypoxia. Consistent with this result, ZFP580 expression was found to be significantly increased in cultured H9c2 myocardial cells in the hypoxic preconditioning group compared with those in the control group following simulated I/R injury (3 h simulated ischemic hypoxia and 2 h reoxygenation). To determine the role of ZFP580 in apoptosis, lentivirus-mediated gene transfection was performed in H9c2 cells 72 h prior to simulated I/R exposure. The results showed that ZFP580 overexpression significantly inhibited I/R-induced apoptosis and caspase-3 activation. H9c2 cells were pretreated with or without PD98059, an inhibitor of ERK1/2 phosphorylation, and Western blot results showed that PD98059 (10 µM) markedly suppressed I/R-induced up-regulation of ZFP580 expression. Conclusions Our findings demonstrate that the cardioprotective effect of IHA hypoxia against I/R injury is mediated via ZFP580, a downstream target of ERK1/2 signaling with anti-apoptotic roles in myocardial cells. PMID:24722354

  10. Altitude and endurance training.

    PubMed

    Rusko, Heikki K; Tikkanen, Heikki O; Peltonen, Juha E

    2004-10-01

    The benefits of living and training at altitude (HiHi) for an improved altitude performance of athletes are clear, but controlled studies for an improved sea-level performance are controversial. The reasons for not having a positive effect of HiHi include: (1) the acclimatization effect may have been insufficient for elite athletes to stimulate an increase in red cell mass/haemoglobin mass because of too low an altitude (< 2000-2200 m) and/or too short an altitude training period (<3-4 weeks); (2) the training effect at altitude may have been compromised due to insufficient training stimuli for enhancing the function of the neuromuscular and cardiovascular systems; and (3) enhanced stress with possible overtraining symptoms and an increased frequency of infections. Moreover, the effects of hypoxia in the brain may influence both training intensity and physiological responses during training at altitude. Thus, interrupting hypoxic exposure by training in normoxia may be a key factor in avoiding or minimizing the noxious effects that are known to occur in chronic hypoxia. When comparing HiHi and HiLo (living high and training low), it is obvious that both can induce a positive acclimatization effect and increase the oxygen transport capacity of blood, at least in 'responders', if certain prerequisites are met. The minimum dose to attain a haematological acclimatization effect is > 12 h a day for at least 3 weeks at an altitude or simulated altitude of 2100-2500 m. Exposure to hypoxia appears to have some positive transfer effects on subsequent training in normoxia during and after HiLo. The increased oxygen transport capacity of blood allows training at higher intensity during and after HiLo in subsequent normoxia, thereby increasing the potential to improve some neuromuscular and cardiovascular determinants of endurance performance. The effects of hypoxic training and intermittent short-term severe hypoxia at rest are not yet clear and they require further study.

  11. Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema.

    PubMed

    Eldridge, Marlowe W; Braun, Ruedi K; Yoneda, Ken Y; Walby, William F

    2006-03-01

    Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonuniform hypoxic pulmonary vasoconstriction could add significantly to augment the mechanical stress on the pulmonary microcirculation. We postulated that intense exercise at altitude would result in an augmented permeability edema. We recruited eight endurance athletes and examined their bronchoalveolar lavage fluid (BALF) for red blood cells (RBCs), protein, inflammatory cells, and soluble mediators at 2 and 26 h after intense exercise under normoxic and hypoxic conditions. After heavy exercise, under all conditions, the athletes developed a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. We found that exercise at altitude (3,810 m) caused significantly greater leakage of RBCs [9.2 (SD 3.1)x10(4) cells/ml] into the alveolar space than that seen with normoxic exercise [5.4 (SD 1.2)x10(4) cells/ml]. At altitude, the 26-h postexercise BALF revealed significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. Interestingly, the BALF profiles following exercise at altitude are similar to that of early high-altitude pulmonary edema. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.

  12. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial.

    PubMed

    Ghofrani, Hossein A; Reichenberger, Frank; Kohstall, Markus G; Mrosek, Eike H; Seeger, Timon; Olschewski, Horst; Seeger, Werner; Grimminger, Friedrich

    2004-08-03

    Alveolar hypoxia causes pulmonary hypertension and enhanced right ventricular afterload, which may impair exercise tolerance. The phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. To investigate the effects of sildenafil on exercise capacity under conditions of hypoxic pulmonary hypertension. Randomized, double-blind, placebo-controlled crossover study. University Hospital Giessen, Giessen, Germany, and the base camp on Mount Everest. 14 healthy mountaineers and trekkers. Systolic pulmonary artery pressure, cardiac output, and peripheral arterial oxygen saturation at rest and during assessment of maximum exercise capacity on cycle ergometry 1) while breathing a hypoxic gas mixture with 10% fraction of inspired oxygen at low altitude (Giessen) and 2) at high altitude (the Mount Everest base camp). Oral sildenafil, 50 mg, or placebo. At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% (95% CI, 66.5% to 77.5%) at rest and 60.8% (CI, 56.0% to 64.5%) at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg (CI, 26.0 to 35.0 mm Hg) at rest to 42.9 mm Hg (CI, 35.6 to 53.5 mm Hg) during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (P = 0.005) and reduced systolic pulmonary artery pressure at rest (P < 0.001) and during exercise (P = 0.031). Of note, sildenafil increased maximum workload (172.5 W [CI, 147.5 to 200.0 W]) vs. 130.6 W [CI, 108.8 to 150.0 W]); P < 0.001) and maximum cardiac output (P < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (P = 0.003) and during exercise (P = 0.021) and increased maximum workload (P = 0.002) and cardiac output (P = 0.015). At high altitude, sildenafil exacerbated existing headache

  13. High Altitude Pulmonary Hypertension: Role of K+ and Ca2+ Channels

    PubMed Central

    Remillard, Carmelle V.; Yuan, Jason X.-J.

    2006-01-01

    Global alveolar hypoxia, as experienced at high-altitude living, has a serious impact on vascular physiology, particular on the pulmonary vasculature. The effects of sustained hypoxia on pulmonary arteries include sustained vasoconstriction and enhanced medial hypertrophy. As the major component of the vascular media, pulmonary artery smooth muscle cells (PASMC) are the main effectors of the physiological response(s) induced during or following hypoxic exposure. Endothelial cells, on the other hand, can sense humoral and haemodynamic changes incurred by hypoxia, triggering their production of vasoactive and mitogenic factors that then alter PASMC function and growth. Transmembrane ion flux through channels in the plasma membrane not only modulates excitation-contraction coupling in PASMC, but also regulates cell volume, apoptosis, and proliferation. In this review, we examine the roles of K+ and Ca2+ channels in the pulmonary vasoconstriction and vascular remodeling observed during chronic hypoxia-induced pulmonary hypertension. PMID:16060848

  14. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751; Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissuesmore » that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes.

  15. Acute hypoxia and related symptoms on mild exertion at simulated altitudes below 3048 m.

    PubMed

    Smith, Adrian M

    2007-10-01

    Helicopter aircrew have reported features of hypoxia below 3048 m (10,000 ft). The aim of this study was to examine the effect of physical activity below 3048 m on the development of hypoxia. Six subjects exercised at 30 W and 60 W for 4 min at sea level, 610 m, 2134 m, and 2743 m (2000 ft, 7000 ft, and 9000 ft). There was an abrupt decrease in Spo2 once physical activity was commenced. This was small at sea level (1%) and 610 m (2.2%), however, the Spo2 fell by 4.3% at 2134 m and 5.5% at 2743 m (to Spo2 88.1% and 85.7%, respectively). Spo2 returned to near-resting values within 3 min of stopping exercise. Symptoms of hypoxia were reported significantly more frequently during activity than rest at each of the altitudes. Helicopter aircrew should be aware that physical activity as low as 2134 m can produce hypoxemia and symptoms of hypoxia similar to that which would normally be expected in a person resting at approximately 3658-4572 m (12,000-15,000 ft).

  16. Chronic intermittent high altitude exposure, occupation, and body mass index in workers of mining industry.

    PubMed

    Esenamanova, Marina K; Kochkorova, Firuza A; Tsivinskaya, Tatyana A; Vinnikov, Denis; Aikimbaev, Kairgeldy

    2014-09-01

    The obesity and overweight rates in population exposed to chronic intermittent exposure to high altitudes are not well studied. The aim of the retrospective study was to evaluate whether there are differences in body mass index in different occupation groups working in intermittent shifts at mining industry at high altitude: 3800-4500 meters above sea level. Our study demonstrated that obesity and overweight are common in workers of high altitude mining industry exposed to chronic intermittent hypoxia. The obesity rate was lowest among miners as compared to blue- and white-collar employees (9.5% vs. 15.6% and 14.7%, p=0.013). Obesity and overweight were associated with older age, higher rates of increased blood pressure (8.79% and 5.72% vs. 1.92%), cholesterol (45.8% and 45.6% vs. 32.8%) and glucose (4.3% and 1.26% vs. 0.57%) levels as compared to normal body mass index category (p<0.0001 for all). There were differences in patterns of cholesterol and glucose levels in men and women employees according to occupation type. In conclusion, obesity and overweight rates are prevalent and associated with increase in blood pressure, cholesterol, and glucose levels in workers of mining industry exposed to intermittent high-altitude hypoxia. Therefore, assessment and monitoring of body mass index seems to be essential in those who live and work at high altitudes to supply the correct nutrition, modify risk factors, and prevent related disorders.

  17. Comparative analysis of the microRNA transcriptome between yak and cattle provides insight into high-altitude adaptation.

    PubMed

    Guan, Jiuqiang; Long, Keren; Ma, Jideng; Zhang, Jinwei; He, Dafang; Jin, Long; Tang, Qianzi; Jiang, Anan; Wang, Xun; Hu, Yaodong; Tian, Shilin; Jiang, Zhi; Li, Mingzhou; Luo, Xiaolin

    2017-01-01

    Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species. The further analysis revealed that both tissues showed relatively high correlation coefficient between yak and cattle, but a greater differentiation was present in lung than heart between the two species. In addition, miRNAs with significantly differentiated patterns of expression in two tissues exhibited co-operation effect in high altitude adaptation based on miRNA family and cluster. Functional analysis revealed that differentially expressed miRNAs were enriched in hypoxia-related pathways, such as the HIF-1α signaling pathway, the insulin signaling pathway, the PI3K-Akt signaling pathway, nucleotide excision repair, cell cycle, apoptosis and fatty acid metabolism, which indicated the important roles of miRNAs in high altitude adaptation. These results suggested the diverse degrees of miRNA transcriptome variation in different tissues between yak and cattle, and suggested extensive roles of miRNAs in high altitude adaptation.

  18. Comparative analysis of the microRNA transcriptome between yak and cattle provides insight into high-altitude adaptation

    PubMed Central

    Zhang, Jinwei; He, Dafang; Jin, Long; Tang, Qianzi; Jiang, Anan; Wang, Xun; Hu, Yaodong; Tian, Shilin; Jiang, Zhi

    2017-01-01

    Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species. The further analysis revealed that both tissues showed relatively high correlation coefficient between yak and cattle, but a greater differentiation was present in lung than heart between the two species. In addition, miRNAs with significantly differentiated patterns of expression in two tissues exhibited co-operation effect in high altitude adaptation based on miRNA family and cluster. Functional analysis revealed that differentially expressed miRNAs were enriched in hypoxia-related pathways, such as the HIF-1α signaling pathway, the insulin signaling pathway, the PI3K-Akt signaling pathway, nucleotide excision repair, cell cycle, apoptosis and fatty acid metabolism, which indicated the important roles of miRNAs in high altitude adaptation. These results suggested the diverse degrees of miRNA transcriptome variation in different tissues between yak and cattle, and suggested extensive roles of miRNAs in high altitude adaptation. PMID:29109913

  19. Long-Term Intermittent Exposure to High Altitude Elevates Asymmetric Dimethylarginine in First Exposed Young Adults.

    PubMed

    Lüneburg, Nicole; Siques, Patricia; Brito, Julio; De La Cruz, Juan José; León-Velarde, Fabiola; Hannemann, Juliane; Ibanez, Cristian; Böger, Rainer H

    2017-09-01

    Lüneburg, Nicole, Patricia Siques, Julio Brito, Juan José De La Cruz, Fabiola León-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Böger. Long-term intermittent exposure to high altitude elevates asymmetric dimethylarginine in first exposed young adults. High Alt Med Biol. 18:226-233, 2017.-Hypoxia-induced dysregulation of pulmonary and cerebral circulation may be related to an impaired nitric oxide (NO) pathway. We investigated the effect of chronic intermittent hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA) and assessed their associations with acclimatization in male draftees (n = 72) undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased from 1.14 ± 0.04 to 1.95 ± 0.09 μmol/L (mean ± SE) and from 0.22 ± 0.07 to 0.39 ± 0.03 μmol/L, respectively, (p < 0.001 for both) after 3 months, whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in CH (3.48 ± 0.07, 0.53 ± 0.08 μmol/L; p < 0.001) as compared with CIH. In both CIH and CH, ADMA correlated with hematocrit (r 2  = 0.07, p < 0.05; r 2  = 0.26; p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L-NMMA, are elevated in hypoxia. This may contribute to impaired NO production at altitude and may also be predictive of altitude-associated health impairment.

  20. Long-Term Intermittent Exposure to High Altitude Elevates Asymmetric Dimethylarginine in First Exposed Young Adults

    PubMed Central

    Siques, Patricia; Brito, Julio; De La Cruz, Juan José; León-Velarde, Fabiola; Hannemann, Juliane; Ibanez, Cristian; Böger, Rainer H.

    2017-01-01

    Abstract Lüneburg, Nicole, Patricia Siques, Julio Brito, Juan José De La Cruz, Fabiola León-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Böger. Long-term intermittent exposure to high altitude elevates asymmetric dimethylarginine in first exposed young adults. High Alt Med Biol. 18:226–233, 2017.—Hypoxia-induced dysregulation of pulmonary and cerebral circulation may be related to an impaired nitric oxide (NO) pathway. We investigated the effect of chronic intermittent hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA) and assessed their associations with acclimatization in male draftees (n = 72) undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased from 1.14 ± 0.04 to 1.95 ± 0.09 μmol/L (mean ± SE) and from 0.22 ± 0.07 to 0.39 ± 0.03 μmol/L, respectively, (p < 0.001 for both) after 3 months, whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in CH (3.48 ± 0.07, 0.53 ± 0.08 μmol/L; p < 0.001) as compared with CIH. In both CIH and CH, ADMA correlated with hematocrit (r2 = 0.07, p < 0.05; r2 = 0.26; p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L-NMMA, are elevated in hypoxia. This may contribute to impaired NO production at altitude and may also be predictive of altitude-associated health impairment. PMID:28453332

  1. Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs

    PubMed Central

    Terry, Michael H.; Merritt, Travis A.; Papamatheakis, Demosthenes G.; Blood, Quintin; Ross, Jonathon M.; Power, Gordon G.; Longo, Lawrence D.; Wilson, Sean M.

    2013-01-01

    Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca2+ entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin. PMID:23152110

  2. Physiological Adjustments and Circulating MicroRNA Reprogramming Are Involved in Early Acclimatization to High Altitude in Chinese Han Males

    PubMed Central

    Liu, Bao; Huang, He; Wang, Shou-Xian; Wu, Gang; Xu, Gang; Sun, Bing-Da; Zhang, Er-Long; Gao, Yu-Qi

    2016-01-01

    Background: Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization could help understand the beneficial body responses to high altitude hypoxia as well as the altered biological events in un-acclimatized individuals. This study assessed physiological adjustments and circulating microRNA (cmiRNA) profiles in individuals exposed to high altitude, aiming to explore altitude acclimatization in humans. Methods: Ninety volunteers were enrolled in this study. Among them, 22 individuals provided samples for microRNA arrays; 68 additional individuals constituted the validation set. Un-acclimatized individuals were identified by the Lake Louise Scoring System. Thirty-three phenotypes were recorded pre- and post-exposure to high altitude, including stress hormones, lipid profiles, hematological indices, myocardial enzyme spectrum, and liver and kidney function related enzymes. CmiRNA expression profiles were assessed using miRCURYTM LNA Array (v.18.0) screening, with data validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, associations of plasma microRNA expression with physiological adjustments were evaluated. The biological relevance of the main differentially expressed cmiRNAs was explored by bioinformatics prediction. Results: Nineteen of the 33 phenotypes were significantly altered during early altitude acclimatization, including hematological indices, lipid profiles, and stress hormones; meanwhile, 86 cmiRNAs (79 up-regulated and 7 down-regulated) showed differential expression with statistical significance. Among them, 32 and 25 microRNAs were strongly correlated with low-density lipoprotein-cholesterol and total cholesterol elevations, respectively. In addition, 22 microRNAs were closely correlated

  3. Abundance of Plasma Antioxidant Proteins Confers Tolerance to Acute Hypobaric Hypoxia Exposure

    PubMed Central

    Padhy, Gayatri; Sethy, Niroj Kumar; Ganju, Lilly

    2013-01-01

    Abstract Padhy, Gayatri, Niroj Kumar Sethy, Lilly Ganju, and Kalpana Bhargava. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure. High Alt Med Biol 14:289–297, 2013—Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies. PMID:24067188

  4. AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

    PubMed

    Subudhi, Andrew W; Bourdillon, Nicolas; Bucher, Jenna; Davis, Christopher; Elliott, Jonathan E; Eutermoster, Morgan; Evero, Oghenero; Fan, Jui-Lin; Jameson-Van Houten, Sonja; Julian, Colleen G; Kark, Jonathan; Kark, Sherri; Kayser, Bengt; Kern, Julia P; Kim, See Eun; Lathan, Corinna; Laurie, Steven S; Lovering, Andrew T; Paterson, Ryan; Polaner, David M; Ryan, Benjamin J; Spira, James L; Tsao, Jack W; Wachsmuth, Nadine B; Roach, Robert C

    2014-01-01

    An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

  5. AltitudeOmics: The Integrative Physiology of Human Acclimatization to Hypobaric Hypoxia and Its Retention upon Reascent

    PubMed Central

    Subudhi, Andrew W.; Bourdillon, Nicolas; Bucher, Jenna; Davis, Christopher; Elliott, Jonathan E.; Eutermoster, Morgan; Evero, Oghenero; Fan, Jui-Lin; Houten, Sonja Jameson-Van; Julian, Colleen G.; Kark, Jonathan; Kark, Sherri; Kayser, Bengt; Kern, Julia P.; Kim, See Eun; Lathan, Corinna; Laurie, Steven S.; Lovering, Andrew T.; Paterson, Ryan; Polaner, David M.; Ryan, Benjamin J.; Spira, James L.; Tsao, Jack W.; Wachsmuth, Nadine B.; Roach, Robert C.

    2014-01-01

    An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention. PMID:24658407

  6. Effect of high altitude on sensitivity to the taste of phenylthiocarbamide

    NASA Astrophysics Data System (ADS)

    Singh, S. B.; Chatterjee, A.; Panjwani, U.; Yadav, D. K.; Selvamurthy, W.; Sharma, K. N.

    Sensitivity to the taste of phenylthiocarbamide (PTC) was studied using the Harris-Kalmus method in healthy human volunteers at sea level and then subsequently at an altitude of 3500 m over a period of 3 weeks, after which they were brought back to sea level. Blood sugar, insulin and blood cortisol levels were estimated weekly. The results indicated that, out of 51 subjects studied, 26 (55%) were PTC tasters at sea level. Eight of those unable to taste PTC at sea level tested as tasters at high altitude, and 2 of them reverted to being non-tasters on return to sea level. In the blood, an increase in cortisol and blood insulin levels was seen without any significant change in sugar levels. All the changes recorded at high altitude tended to return to basal values after re-induction to sea level. The study suggests that high-altitude hypoxia in some way, possibly involving changes in hormonal profile among other factors, causes an alteration in sensitivity to the taste of PTC, resulting in some of the individuals shifting to lower PTC sensitivity.

  7. High-altitude adaptation of Tibetan chicken from MT-COI and ATP-6 perspective.

    PubMed

    Zhao, Xiaoling; Wu, Nan; Zhu, Qing; Gaur, Uma; Gu, Ting; Li, Diyan

    2016-09-01

    The problem of hypoxia adaptation in high altitudes is an unsolved brainteaser in the field of life sciences. As one of the best chicken breeds with adaptability to highland environment, the Tibetan chicken, is genetically different from lowland chicken breeds. In order to gain a better understanding of the mechanism of hypoxic adaptability in high altitude, in the present study, we focused on the MT-COI together with ATP-6 gene to explore the regulatory mechanisms for hypoxia adaptability in Tibet chicken. Here, we sequenced MT-COI of 29 Tibetan chickens and 30 Chinese domestic chickens and ATP-6 gene of 28 Tibetan chickens and 29 Chinese domestic chickens. In MT-COI gene, 9 single nucleotide polymorphisms (SNPs) were detected though none of these was a missense mutation, confirming the fact that MT-COI gene is a largely conservative sequence. In ATP-6 gene, 6 single nucleotide polymorphisms (SNPs) were detected and we found a missense mutation (m.9441G > A) in the ATP-6 gene of Tibetan chicken resulting in an amino acid substitution. Due to the critical role of ATP-6 gene in the proton translocation and energy metabolism, we speculated the possibility of this mutation playing an important role in easier energy conversion and metabolism in Tibetan chickens than Chinese domestic chickens so as to better adapt to the harsh environment of the high-altitude areas. The Median-joining profile also suggested that haplotype Ha2 has the ancestral position to the other haplotypes and has significant relationship with high-altitude adaptation in ATP-6 gene. Therefore, we considered that the polymorphism (m.9441G > A) in the ATP-6 gene may affect the specific functions of ATP-6 enzyme relating to high-altitude adaptation of Tibetan chicken and MT-COI gene is a largely conservative sequence.

  8. Human nutrition in cold and high terrestrial altitudes

    NASA Astrophysics Data System (ADS)

    Srivastava, K. K.; Kumar, Ratan

    1992-03-01

    The calorie and nutritional requirements for a man working in an alien hostile environment of cold regions and high altitude are described and compared to those of normal requirements. Carbohydrates, fats and vitamins fulfilling the caloric and nutritional requirements are generally available in adequate amounts except under conditions of appetite loss. However, the proteins and amino acids should be provided in such a way as to meet the altered behavioral and metabolic requirements. Work in extreme cold requires fulfilling enhanced calorie needs. In high mountainous regions, cold combined with hypoxia produced loss of appetite and necessitated designing of special foods.

  9. High Resolution ECG for Evaluation of Heart Function During Exposure to Subacute Hypobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, Petra; Finderle, Zarko; Schlegel, Todd T.; Princi, Tanja; Starc, Vito

    2010-01-01

    High altitude climbing presents a wide spectrum of health risks, including exposure to hypobaric hypoxia. Risks are also typically exacerbated by the difficulty in appropriately monitoring for early signs of organ dysfunction in remote areas. We investigated whether high resolution advanced ECG analysis might be helpful as a non-invasive and easy-to-use tool (e.g., instead of Doppler echocardiography) for evaluating early signs of heart overload in hypobaric hypoxia. Nine non-acclimatized healthy trained alpine rescuers (age 43.7 plus or minus 7.3 years) climbed in four days to the altitude of 4,200 m on Mount Ararat. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position on different days but at the same time of day at four different altitudes: 400 m (reference altitude), 1,700 m, 3,200 m and 4,200 m. Changes in conventional and advanced resting ECG parameters, including in beat-to-beat QT and RR variability, waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG was estimated by calculation of the regression coefficients in independent linear regression models. A p-value of less than 0.05 was adopted as statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with trends k = -96 ms/1000 m with p = 0.000 and k = -9 ms/1000 m with p = 0.001, respectively. Significant changes were found in P-wave amplitude, which nearly doubled from the lowest to the highest altitude (k = 41.6 microvolt/1000 m with p = 0.000), and nearly significant changes in P-wave duration (k = 2.9 ms/1000 m with p = 0.059). Changes were less significant or non-significant in other studied parameters including those of waveform complexity, signal-averaged, high-frequency and spatial/spatiotemporal ECG. High resolution ECG analysis, particularly of the P wave, shows promise as a tool for monitoring early changes in heart function

  10. Oxygen transport of hemoglobin in high-altitude animals (Camelidae).

    PubMed

    Reynafarje, C; Faura, J; Villavicencio, D; Curaca, A; Reynafarje, B; Oyola, L; Contreras, L; Vallenas, E; Faura, A

    1975-05-01

    To clarify the mechanisms by which high-altitude Camelidae can adapt to hypoxia, the study of some blood characteristics were carried out in apacas and llamas. The results show that there is a peculiar dissociation curve of hemoglobin in alpacas which permits great affinity of hemoglobin for oxygen at lung level and the release of oxygen at the tissue level with a facility similar to that in man. Fetal hemoglobin was found high in adult alpacas (55 percent). Electrophoretic studies of hemoglobin showed that this pigment has two components, both of which have a very low mobility. Lactic dehydrogenase was found six times higher than in humans. RBC glucose-6-phosphate dehydrogenase was two times higher than in man living at the same altitude. Myoglobin was found to be higher than in man living at altitude. Alpacas have erythrocytes in which the amount of 2,3-DPG is approximately the same as in man. RBC are more resistent to hypotonic solutions than humans. The amount of lactic dehydrogenase, myoglobin, and glucose-6-phosphate dehydrogenase dimishes when alpacas are bought down to sea level.

  11. Growth trends among male Bods of Ladakh--a high altitude population.

    PubMed

    Malik, S L; Singh, I P

    1978-02-01

    A random sample of 274 native male Bods of Ladakh ranging in age from 11 to 19 years, living in Leh (Ladakh) at mean altitude of 3,514 metres, was studied. The pattern of growth of this sample was compared with the sea level Indians. The results indicate that: (1) The so called adolescent spurt is not well defined among Bod highlanders. (2) Bods grow faster than plain dwelling Indians and are taller and heavier at the age of 19 years. (3) The highlanders exhibit greater chest circumference than the lowland norms. This finding, similar to those among Andean natives, supports high altitude hypoxia's role in human growth and morphology.

  12. Autonomic Cardiovascular Responses in Acclimatized Lowlanders on Prolonged Stay at High Altitude: A Longitudinal Follow Up Study

    PubMed Central

    Dhar, Priyanka; Sharma, Vijay K.; Hota, Kalpana B.; Das, Saroj K.; Hota, Sunil K.; Srivastava, Ravi B.; Singh, Shashi B.

    2014-01-01

    Acute exposure to hypobaric hypoxia at high altitude is reported to cause sympathetic dominance that may contribute to the pathophysiology of high altitude illnesses. The effect of prolonged stay at high altitude on autonomic functions, however, remains to be explored. Thus, the present study aimed at investigating the effect of high altitude on autonomic neural control of cardiovascular responses by monitoring heart rate variability (HRV) during chronic hypobaric hypoxia. Baseline electrocardiography (ECG) data was acquired from the volunteers at mean sea level (MSL) (<250 m) in Rajasthan. Following induction of the study population to high altitude (4500–4800 m) in Ladakh region, ECG data was acquired from the volunteers after 6 months (ALL 6) and 18 months of induction (ALL 18). Out of 159 volunteers who underwent complete investigation during acquisition of baseline data, we have only included the data of 104 volunteers who constantly stayed at high altitude for 18 months to complete the final follow up after 18 months. HRV parameters, physiological indices and biochemical changes in serum were investigated. Our results show sympathetic hyperactivation along with compromise in parasympathetic activity in ALL 6 and ALL 18 when compared to baseline data. Reduction of sympathetic activity and increased parasympathetic response was however observed in ALL 18 when compared to ALL 6. Our findings suggest that autonomic response is regulated by two distinct mechanisms in the ALL 6 and ALL 18. While the autonomic alterations in the ALL 6 group could be attributed to increased sympathetic activity resulting from increased plasma catecholamine concentration, the sympathetic activity in ALL 18 group is associated with increased concentration of serum coronary risk factors and elevated homocysteine. These findings have important clinical implications in assessment of susceptibility to cardio-vascular risks in acclimatized lowlanders staying for prolonged duration at high

  13. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  14. Effects of altitude-related hypoxia on aircrews in aircraft with unpressurized cabins.

    PubMed

    Nishi, Shuji

    2011-01-01

    Generally, hypoxia at less than 10,000 ft (3,048 m) has no apparent effect on aircrews. Nevertheless, several hypoxic incidents have been reported in flights below 10,000 ft. A recently introduced pulse oximeter using finger probes allows accurate monitoring of oxygen saturation (SPO2) in the aeromedical environment. Using such a pulse oximeter, in-flight SPO2 levels were evaluated in aircrew in unpressurized aircraft. In addition, career in-flight hypoxic experiences were surveyed. In-flight SPO2 was measured in aircrews operating UH-60J helicopters at up to 13,000 ft, and 338 aircrew members operating unpressurized cabin aircraft were surveyed concerning possible in-flight hypoxic experiences. In aircrews operating UH-60J helicopters, SPO2 decreased significantly at altitudes over 5,000 ft, most markedly at 13,000 ft (vs. ground level). The survey identified three aircrew members with experiences suggesting hypoxemia at below 5,000 ft. Careful attention should be paid to the possibility of hypoxia in aircrews operating unpressurized cabin aircraft.

  15. Different gene expressions between cattle and yak provide insights into high-altitude adaptation.

    PubMed

    Wang, K; Yang, Y; Wang, L; Ma, T; Shang, H; Ding, L; Han, J; Qiu, Q

    2016-02-01

    DNA sequence variation has been widely reported as the genetic basis for adaptation, in both humans and other animals, to the hypoxic environment experienced at high altitudes. However, little is known about the patterns of gene expression underlying such hypoxic adaptations. In this study, we examined the differences in the transcriptomes of four organs (heart, kidney, liver and lung) between yak and cattle, a pair of closely related species distributed at high and low altitudes respectively. Of the four organs examined, heart shows the greatest differentiation between the two species in terms of gene expression profiles. Detailed analyses demonstrated that some genes associated with the oxygen supply system and the defense systems that respond to threats of hypoxia are differentially expressed. In addition, genes with significantly differentiated patterns of expression in all organs exhibited an unexpected uniformity of regulation along with an elevated frequency of nonsynonymous substitutions. This co-evolution of protein sequences and gene expression patterns is likely to be correlated with the optimization of the yak metabolic system to resist hypoxia. © 2015 Stichting International Foundation for Animal Genetics.

  16. Sleep Disordered Breathing During Live High-Train Low in Normobaric Versus Hypobaric Hypoxia.

    PubMed

    Saugy, Jonas J; Schmitt, Laurent; Fallet, Sibylle; Faiss, Raphael; Vesin, Jean-Marc; Bertschi, Mattia; Heinzer, Raphaël; Millet, Grégoire P

    2016-09-01

    Saugy, Jonas J., Laurent Schmitt, Sibylle Fallet, Raphael Faiss, Jean-Marc Vesin, Mattia Bertschi, Raphaël Heinzer, and Grégoire P. Millet. Sleep disordered breathing during live high-train low in normobaric versus hypobaric hypoxia. High Alt Med Biol. 17:233-238, 2016.-The present study aimed to compare sleep disordered breathing during live high-train low (LHTL) altitude camp using normobaric hypoxia (NH) and hypobaric hypoxia (HH). Sixteen highly trained triathletes completed two 18-day LHTL camps in a crossover designed study. They trained at 1100-1200 m while they slept either in NH at a simulated altitude of 2250 m or in HH. Breathing frequency and oxygen saturation (SpO 2 ) were recorded continuously during all nights and oxygen desaturation index (ODI 3%) calculated. Breathing frequency was lower for NH than HH during the camps (14.6 ± 3.1 breath × min -1 vs. 17.2 ± 3.4 breath × min -1 , p < 0.001). SpO 2 was lower for HH than NH (90.8 ± 0.3 vs. 91.9 ± 0.2, p < 0.001) and ODI 3% was higher for HH than NH (15.1 ± 3.5 vs. 9.9 ± 1.6, p < 0.001). Sleep in moderate HH is more altered than in NH during a LHTL camp.

  17. Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors

    PubMed Central

    Brito, Julio; Siques, Patricia; López, Rosario; Romero, Raul; León-Velarde, Fabiola; Flores, Karen; Lüneburg, Nicole; Hannemann, Juliane; Böger, Rainer H.

    2018-01-01

    Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400–4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5–29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3–5 points, including cephalea; moderate was LLS of 6–10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18–66.39); p < 0.05) and insulin (OR: 1.11 (1.02–1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and

  18. Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors.

    PubMed

    Brito, Julio; Siques, Patricia; López, Rosario; Romero, Raul; León-Velarde, Fabiola; Flores, Karen; Lüneburg, Nicole; Hannemann, Juliane; Böger, Rainer H

    2018-01-01

    Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400-4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5-29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3-5 points, including cephalea; moderate was LLS of 6-10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18-66.39); p < 0.05) and insulin (OR: 1.11 (1.02-1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel

  19. Tracking performance with two breathing oxygen concentrations after high altitude rapid decompression

    NASA Technical Reports Server (NTRS)

    Nesthus, Thomas E.; Schiflett, Samuel G.; Oakley, Carolyn J.

    1992-01-01

    Current military aircraft Liquid Oxygen (LOX) systems supply 99.5 pct. gaseous Aviator's Breathing Oxygen (ABO) to aircrew. Newer Molecular Sieve Oxygen Generation Systems (MSOGS) supply breathing gas concentration of 93 to 95 pct. O2. The margin is compared of hypoxia protection afforded by ABO and MSOGS breathing gas after a 5 psi differential rapid decompression (RD) in a hypobaric research chamber. The barometric pressures equivalent to the altitudes of 46000, 52000, 56000, and 60000 ft were achieved from respective base altitudes in 1 to 1.5 s decompressions. During each exposure, subjects remained at the simulated peak altitude breathing either 100 or 94 pct. O2 with positive pressure for 60 s, followed by a rapid descent to 40000 ft. Subjects used the Tactical Life Support System (TLSS) for high altitude protection. Subcritical tracking task performance on the Performance Evaluation Device (PED) provided psychomotor test measures. Overall tracking task performance results showed no differences between the MSOGS breathing O2 concentration of 94 pct. and ABO. Significance RMS error differences were found between the ground level and base altitude trials compared to peak altitude trials. The high positive breathing pressures occurring at the peak altitudes explained the differences.

  20. Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano.

    PubMed

    Herrera, Emilio A; Rojas, Rodrigo T; Krause, Bernardo J; Ebensperger, Germán; Reyes, Roberto V; Giussani, Dino A; Parer, Julian T; Llanos, Aníbal J

    2016-03-01

    High-altitude hypoxia causes intrauterine growth restriction and cardiovascular programming. However, adult humans and animals that have evolved at altitude show certain protection against the effects of chronic hypoxia. Whether the highland fetus shows similar protection against high altitude gestation is unclear. We tested the hypothesis that high-altitude fetal sheep have evolved cardiovascular compensatory mechanisms to withstand chronic hypoxia that are different from lowland sheep. We studied seven high-altitude (HA; 3600 m) and eight low-altitude (LA; 520 m) pregnant sheep at ∼90% gestation. Pregnant ewes and fetuses were instrumented for cardiovascular investigation. A three-period experimental protocol was performed in vivo: 30 min of basal, 1 h of acute superimposed hypoxia (∼10% O2) and 30 min of recovery. Further, we determined ex vivo fetal cerebral and femoral arterial function. HA pregnancy led to chronic fetal hypoxia, growth restriction and altered cardiovascular function. During acute superimposed hypoxia, LA fetuses redistributed blood flow favouring the brain, heart and adrenals, whereas HA fetuses showed a blunted cardiovascular response. Importantly, HA fetuses have a marked reduction in umbilical blood flow versus LA. Isolated cerebral arteries from HA fetuses showed a higher contractile capacity but a diminished response to catecholamines. In contrast, femoral arteries from HA fetuses showed decreased contractile capacity and increased adrenergic contractility. The blunting of the cardiovascular responses to hypoxia in fetuses raised in the Alto Andino may indicate a change in control strategy triggered by chronic hypoxia, switching towards compensatory mechanisms that are more cost-effective in terms of oxygen uptake. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  1. Changing Patterns of Neuropsychological Functioning in Children Living at High Altitude above and below 4000 M: A Report from the Bolivian Children Living at Altitude (BoCLA) Study

    ERIC Educational Resources Information Center

    Virues-Ortega, Javier; Bucks, Romola; Kirkham, Fenella J.; Baldeweg, Torsten; Baya-Botti, Ana; Hogan, Alexandra M.

    2011-01-01

    The brain is highly sensitive to environmental hypoxia. Little is known, however, about the neuropsychological effects of high altitude residence in the developing brain. We recently described only minor changes in processing speed in native Bolivian children and adolescents living at approximately 3700 m. However, evidence for loss of cerebral…

  2. Changes in sleep quality of athletes under normobaric hypoxia equivalent to 2,000-m altitude: a polysomnographic study.

    PubMed

    Hoshikawa, Masako; Uchida, Sunao; Sugo, Takayuki; Kumai, Yasuko; Hanai, Yoshiteru; Kawahara, Takashi

    2007-12-01

    This study evaluated the sleep quality of athletes in normobaric hypoxia at a simulated altitude of 2,000 m. Eight male athletes slept in normoxic condition (NC) and hypoxic conditions equivalent to those at 2,000-m altitude (HC). Polysomnographic recordings of sleep included the electroencephalogram (EEG), electrooculogram, chin surface electromyogram, and electrocardiogram. Thoracic and abdominal motion, nasal and oral airflow, and arterial blood oxygen saturation (Sa(O(2))) were also recorded. Standard visual sleep stage scoring and fast Fourier transformation analyses of the EEG were performed on 30-s epochs. Subjective sleepiness and urinary catecholamines were also monitored. Mean Sa(O(2)) decreased and respiratory disturbances increased with HC. The increase in respiratory disturbances was significant, but the increase was small and subclinical. The duration of slow-wave sleep (stage 3 and 4) and total delta power (<3 Hz) of the all-night non-rapid eye movement sleep EEG decreased for HC compared with NC. Subjective sleepiness and amounts of urinary catecholamines did not differ between the conditions. These results indicate that acute exposure to normobaric hypoxia equivalent to that at 2,000-m altitude decreased slow-wave sleep in athletes, but it did not change subjective sleepiness or amounts of urinary catecholamines.

  3. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia

    PubMed Central

    Hansen, Jim; Sander, Mikael

    2003-01-01

    Acute exposure to hypoxia causes chemoreflex activation of the sympathetic nervous system. During acclimatization to high altitude hypoxia, arterial oxygen content recovers, but it is unknown to what degree sympathetic activation is maintained or normalized during prolonged exposure to hypoxia. We therefore measured sympathetic nerve activity directly by peroneal microneurography in eight healthy volunteers (24 ± 2 years of age) after 4 weeks at an altitude of 5260 m (Chacaltaya, Bolivian Andes) and at sea level (Copenhagen). The subjects acclimatized well to altitude, but in every subject sympathetic nerve activity was highly elevated at altitude vs. sea level (48 ± 5 vs. 16 ± 3 bursts min−1, respectively, P < 0.05), coinciding with increased mean arterial blood pressure (87 ± 3 vs. 77 ± 2 mmHg, respectively, P < 0.05). To examine the underlying mechanisms, we administered oxygen (to eliminate chemoreflex activation) and saline (to reduce cardiopulmonary baroreflex deactivation). These interventions had minor effects on sympathetic activity (48 ± 5 vs. 38 ± 4 bursts min−1, control vs. oxygen + saline, respectively, P < 0.05). Moreover, sympathetic activity was still markedly elevated (37 ± 5 bursts min−1) when subjects were re-studied under normobaric, normoxic and hypervolaemic conditions 3 days after return to sea level. In conclusion, acclimatization to high altitude hypoxia is accompanied by a striking and long-lasting sympathetic overactivity. Surprisingly, chemoreflex activation by hypoxia and baroreflex deactivation by dehydration together could account for only a small part of this response, leaving the major underlying mechanisms unexplained. PMID:12563015

  4. Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude.

    PubMed

    Zhang, Juanling; Zhu, Junbo; Yao, Xingchen; Duan, Yabin; Zhou, Xuejiao; Yang, Meng; Li, Xiangyang

    2016-01-01

    To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 h after study drug administration. Lidocaine hydrochloride in plasma was determined by RP-HPLC. Pharmacokinetics parameters of lidocaine hydrochloride showed that there were no significant difference between the native Han and Tibetan volunteers, but the t(1/2) was 29.8 and 29.8% higher in 2 groups, respectively, than in the LA group. To study related mechanism, the effects of exposure to chronic high-altitude hypoxia (CHH) on the activity and expression of CYP3A1 were examined in rats. Rats were divided into LA, chronic moderate altitude hypoxia, and CHH groups. CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP3A1 in vivo. This study found significant changes in the disposition of lidocaine hydrochloride in native healthy Tibetan and Han Chinese subjects living at a high altitude in comparison to healthy Han Chinese subjects living at LA, it might be due to significant decreases in the activity and protein and mRNA expression of CYP3A4 under CHH condition. © 2016 S. Karger AG, Basel.

  5. Concepts in hypoxia reborn

    PubMed Central

    2010-01-01

    The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies. PMID:20727228

  6. Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude.

    PubMed

    Caravita, Sergio; Faini, Andrea; Baratto, Claudia; Bilo, Grzegorz; Macarlupu, Josè Luis; Lang, Morin; Revera, Miriam; Lombardi, Carolina; Villafuerte, Francisco C; Agostoni, Piergiuseppe; Parati, Gianfranco

    2018-06-09

    Acute exposure to high-altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. Fifty-five subjects with mild hypertension, double-blindly randomized to placebo or to a fixed-dose combination of an angiotensin-receptor blocker (telmisartan 80 mg) and a calcium-channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High-altitude exposure caused both an 8 mm Hg upward shift ( P <0.01) and a 0.4 mm Hg/mL/kg per minute steepening ( P <0.05) of the systolic blood pressure/oxygen consumption relationship during exercise, independent of treatment. Telmisartan/nifedipine did not modify blood pressure reactivity to exercise (blood pressure/oxygen consumption slope), but downward shifted ( P <0.001) the relationship between systolic blood pressure and oxygen consumption by 26 mm Hg, both at sea level and at altitude. Muscle oxygen delivery was not influenced by altitude exposure but was higher on telmisartan/nifedipine than on placebo ( P <0.01). In hypertensive subjects exposed to high altitude, we observed a hypoxia-driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Evaluating the Risks of High Altitude Travel in Chronic Liver Disease Patients.

    PubMed

    Luks, Andrew M; Swenson, Erik R

    2015-06-01

    Luks, Andrew M., and Erik R. Swenson. Clinician's Corner: Evaluating the risks of high altitude travel in chronic liver disease patients. High Alt Med Biol 16:80-88, 2015.--With improvements in the quality of health care, people with chronic medical conditions are experiencing better quality of life and increasingly participating in a wider array of activities, including travel to high altitude. Whenever people with chronic diseases travel to this environment, it is important to consider whether the physiologic responses to hypobaric hypoxia will interact with the underlying medical condition such that the risk of acute altitude illness is increased or the medical condition itself may worsen. This review considers these questions as they pertain to patients with chronic liver disease. While the limited available evidence suggests there is no evidence of liver injury or dysfunction in normal individuals traveling as high as 5000 m, there is reason to suspect that two groups of cirrhosis patients are at increased risk for problems, hepatopulmonary syndrome patients, who are at risk for severe hypoxemia following ascent, and portopulmonary hypertension patients who may be at risk for high altitude pulmonary edema and acute right ventricular dysfunction. While liver transplant patients may tolerate high altitude exposure without difficulty, no information is available regarding the risks of long-term residence at altitude with chronic liver disease. All travelers with cirrhosis require careful pre-travel evaluation to identify conditions that might predispose to problems at altitude and develop risk mitigation strategies for these issues. Patients also require detailed counseling about recognition, prevention, and treatment of acute altitude illness and may require different medication regimens to prevent or treat altitude illness than used in healthy individuals.

  8. A new approach to very-high-altitude land travel: the train to Lhasa, Tibet.

    PubMed

    West, John B

    2008-12-16

    The train from Golmud in Qinghai Province, China, to Lhasa, Tibet, travels for more than 14 hours at an average altitude of 4500 m, the highest point being 5072 m (16,600 ft). Therefore, passengers are potentially exposed to very severe sustained hypoxia. The enterprising solution is to increase the oxygen concentration of the air in the train from 21% to between 24% and 25% by the use of oxygen generators in each passenger car. By increasing the oxygen concentration to 25%, the equivalent altitude is reduced by about 1200 m. The engineering challenge of oxygenating the whole train is immense but has been successfully accomplished. This is an extraordinary innovation in high-altitude transportation.

  9. Evidence for involvement of uncoupling proteins in cerebral mitochondrial oxidative phosphorylation deficiency of rats exposed to 5,000 m high altitude.

    PubMed

    Xu, Yu; Liu, Yuliang; Xia, Chen; Gao, Pan; Liu, Jun-Ze

    2013-02-01

    The present study aimed to investigate the change of proton leak and discuss the role of cerebral uncoupling proteins (UCPs) and its regulatory molecules non-esterified fatty acid (NEFA) in high altitude mitochondrial oxidative phosphorylation deficiency. The model group animals were exposed to acute high altitude hypoxia, and the mitochondrial respiration, protein leak, UCPs abundance/activity and cerebral NEFA concentration were measured. We found that in the model group, cerebral mitochondrial oxidative phosphorylation was severely impaired with decreased ST3 respiration rate and ATP pool. Proton leak kinetics curves demonstrated an increase in proton leak; GTP binding assay pointed out that total cerebral UCPs activity significantly increased; Q-PCR and western blot showed upregulated expression of UCP4 and UCP5. Moreover, cerebral NEFA concentration increased. In conclusion, UCPs mediated proton leak is closely related to cerebral mitochondria oxidative phosphorylation deficiency during acute high altitude hypoxia and NEFA is involved in this signaling pathway.

  10. Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.

    PubMed

    Mariggiò, Maria A; Falone, Stefano; Morabito, Caterina; Guarnieri, Simone; Mirabilio, Alessandro; Pilla, Raffaele; Bucciarelli, Tonino; Verratti, Vittore; Amicarelli, Fernanda

    2010-01-01

    Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

  11. Fit for high altitude: are hypoxic challenge tests useful?

    PubMed

    Matthys, Heinrich

    2011-02-28

    Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or

  12. Simulated altitude exposure assessment by hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Calin, Mihaela Antonina; Macovei, Adrian; Miclos, Sorin; Parasca, Sorin Viorel; Savastru, Roxana; Hristea, Razvan

    2017-05-01

    Testing the human body's reaction to hypoxia (including the one generated by high altitude) is important in aeronautic medicine. This paper presents a method of monitoring blood oxygenation during experimental hypoxia using hyperspectral imaging (HSI) and a spectral unmixing model based on a modified Beer-Lambert law. A total of 20 healthy volunteers (males) aged 25 to 60 years were included in this study. A line-scan HSI system was used to acquire images of the faces of the subjects. The method generated oxyhemoglobin and deoxyhemoglobin distribution maps from the foreheads of the subjects at 5 and 10 min of hypoxia and after recovery in a high oxygen breathing mixture. The method also generated oxygen saturation maps that were validated using pulse oximetry. An interesting pattern of desaturation on the forehead was discovered during the study, showing one of the advantages of using HSI for skin oxygenation monitoring in hypoxic conditions. This could bring new insight into the physiological response to high altitude and may become a step forward in air crew testing.

  13. Simulated altitude exposure assessment by hyperspectral imaging.

    PubMed

    Calin, Mihaela Antonina; Macovei, Adrian; Miclos, Sorin; Parasca, Sorin Viorel; Savastru, Roxana; Hristea, Razvan

    2017-05-01

    Testing the human body’s reaction to hypoxia (including the one generated by high altitude) is important in aeronautic medicine. This paper presents a method of monitoring blood oxygenation during experimental hypoxia using hyperspectral imaging (HSI) and a spectral unmixing model based on a modified Beer–Lambert law. A total of 20 healthy volunteers (males) aged 25 to 60 years were included in this study. A line-scan HSI system was used to acquire images of the faces of the subjects. The method generated oxyhemoglobin and deoxyhemoglobin distribution maps from the foreheads of the subjects at 5 and 10 min of hypoxia and after recovery in a high oxygen breathing mixture. The method also generated oxygen saturation maps that were validated using pulse oximetry. An interesting pattern of desaturation on the forehead was discovered during the study, showing one of the advantages of using HSI for skin oxygenation monitoring in hypoxic conditions. This could bring new insight into the physiological response to high altitude and may become a step forward in air crew testing.

  14. Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

    PubMed Central

    Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R.; Powell, Frank L.

    2016-01-01

    Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease. PMID:26726885

  15. Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.

    PubMed

    Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R; Powell, Frank L

    2016-01-01

    Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.

  16. Changing patterns of neuropsychological functioning in children living at high altitude above and below 4000 m: a report from the Bolivian Children Living at Altitude (BoCLA) study.

    PubMed

    Virués-Ortega, Javier; Bucks, Romola; Kirkham, Fenella J; Baldeweg, Torsten; Baya-Botti, Ana; Hogan, Alexandra M

    2011-09-01

    The brain is highly sensitive to environmental hypoxia. Little is known, however, about the neuropsychological effects of high altitude residence in the developing brain. We recently described only minor changes in processing speed in native Bolivian children and adolescents living at approximately 3700 m. However, evidence for loss of cerebral autoregulation above this altitude (4000 m) suggests a potential threshold of hypoxia severity over which neuropsychological functioning may be compromised. We conducted physiological and neuropsychological assessments in 62 Bolivian children and adolescents living at La Paz (∼3700 m) and El Alto (∼4100 m) in order to address this issue. Groups were equivalent in terms of age, gender, social class, schooling, parental education and genetic admixture. Apart from percentage of hemoglobin saturated with oxygen in arterial blood (%SpO(2)), participants did not differ in their basal cardiac and cerebrovascular performance as explored by heart rate, mean arterial pressure, end-tidal carbon dioxide, and cerebral blood flow velocity at the basilar, anterior, middle and posterior cerebral arteries. A comprehensive neuropsychological assessment was administered, including tests of executive functions, attention, memory and psychomotor performance. Participants living at extreme altitude showed lower levels of performance in all executive tests (Cohen effect size = -0.91), whereas all other domains remained unaffected by altitude of residence. These results are compatible with earlier physiological evidence of a transitional zone for cerebral autoregulation at an altitude of 4000 m. We now show that above this threshold, the developing brain is apparently increasingly vulnerable to neuropsychological deficit. © 2011 Blackwell Publishing Ltd.

  17. Chronic Hypoxia Accentuates Dysanaptic Lung Growth.

    PubMed

    Llapur, Conrado J; Martínez, Myriam R; Grassino, Pedro T; Stok, Ana; Altieri, Héctor H; Bonilla, Federico; Caram, María M; Krowchuk, Natasha M; Kirby, Miranda; Coxson, Harvey O; Tepper, Robert S

    2016-08-01

    Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways.

  18. Teaching the Physiology of Adaptation to Hypoxic Stress with the Aid of a Classic Paper on High Altitude by Houston and Riley

    ERIC Educational Resources Information Center

    Tansey, Etain A.

    2008-01-01

    Many pathological conditions exist where tissues exhibit hypoxia or low oxygen tension. Hypoxic hypoxia arises when there is a reduction in the amount of oxygen entering the blood and occurs in healthy people at high altitude. In 1946, research sponsored by the United States Navy led to the collection and subsequent publication of masses of data…

  19. Metabolic basis to Sherpa altitude adaptation

    PubMed Central

    Horscroft, James A.; Kotwica, Aleksandra O.; Laner, Verena; West, James A.; Hennis, Philip J.; Levett, Denny Z. H.; Howard, David J.; Fernandez, Bernadette O.; Burgess, Sarah L.; Ament, Zsuzsanna; Gilbert-Kawai, Edward T.; Vercueil, André; Landis, Blaine D.; Mythen, Monty G.; Branco, Cristina; Feelisch, Martin; Montgomery, Hugh E.; Griffin, Julian L.; Grocott, Michael P. W.; Gnaiger, Erich; Martin, Daniel S.; Murray, Andrew J.

    2017-01-01

    The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature. PMID:28533386

  20. Hypoxia-Related Hormonal Appetite Modulation in Humans during Rest and Exercise: Mini Review

    PubMed Central

    Debevec, Tadej

    2017-01-01

    Obesity is associated with numerous chronic ailments and represents one of the major health and economic issues in the modernized societies. Accordingly, there is an obvious need for novel treatment approaches. Recently, based on the reports of reduced appetite and subsequent weight loss following high-altitude sojourns, exposure to hypoxia has been proposed as a viable weight-reduction strategy. While altitude-related appetite modulation is complex and not entirely clear, hypoxia-induced alterations in hormonal appetite modulation might be among the key underlying mechanisms. The present paper summarizes the up-to-date research on hypoxia/altitude-induced changes in the gut and adipose tissue derived peptides related to appetite regulation. Orexigenic hormone ghrelin and anorexigenic peptides leptin, glucagon-like peptide-1, peptide YY, and cholecystokinin have to-date been investigated as potential modulators of hypoxia-driven appetite alterations. Current evidence suggests that hypoxia can, especially acutely, lead to decreased appetite, most probably via reduction of acylated ghrelin concentration. Hypoxia-related short and long-term changes in other hormonal markers are more unclear although hypoxia seems to importantly modulate leptin levels, especially following prolonged hypoxic exposures. Limited evidence also suggests that different activity levels during exposures to hypoxia do not additively affect hormonal appetite markers. Although very few studies have been performed in obese/overweight individuals, the available data indicate that hypoxia/altitude exposures do not seem to differentially affect appetite regulation via hormonal pathways in this cohort. Given the lack of experimental data, future well-controlled acute and prolonged studies are warranted to expand our understanding of hypoxia-induced hormonal appetite modulation and its kinetics in health and disease. PMID:28611686

  1. Athletes at High Altitude

    PubMed Central

    Khodaee, Morteza; Grothe, Heather L.; Seyfert, Jonathan H.; VanBaak, Karin

    2016-01-01

    Context: Athletes at different skill levels perform strenuous physical activity at high altitude for a variety of reasons. Multiple team and endurance events are held at high altitude and may place athletes at increased risk for developing acute high altitude illness (AHAI). Training at high altitude has been a routine part of preparation for some of the high level athletes for a long time. There is a general belief that altitude training improves athletic performance for competitive and recreational athletes. Evidence Acquisition: A review of relevant publications between 1980 and 2015 was completed using PubMed and Google Scholar. Study Design: Clinical review. Level of Evidence: Level 3. Results: AHAI is a relatively uncommon and potentially serious condition among travelers to altitudes above 2500 m. The broad term AHAI includes several syndromes such as acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Athletes may be at higher risk for developing AHAI due to faster ascent and more vigorous exertion compared with nonathletes. Evidence regarding the effects of altitude training on athletic performance is weak. The natural live high, train low altitude training strategy may provide the best protocol for enhancing endurance performance in elite and subelite athletes. High altitude sports are generally safe for recreational athletes, but they should be aware of their individual risks. Conclusion: Individualized and appropriate acclimatization is an essential component of injury and illness prevention. PMID:26863894

  2. Increased endothelial microparticles and oxidative stress at extreme altitude.

    PubMed

    Pichler Hefti, Jacqueline; Leichtle, Alexander; Stutz, Monika; Hefti, Urs; Geiser, Thomas; Huber, Andreas R; Merz, Tobias M

    2016-04-01

    Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

  3. Urinary leukotriene E(4) levels are not increased prior to high-altitude pulmonary edema.

    PubMed

    Bärtsch, P; Eichenberger, U; Ballmer, P E; Gibbs, J S; Schirlo, C; Oelz, O; Mayatepek, E

    2000-05-01

    To examine whether increased urinary cysteinyl-leukotriene E(4) (LTE(4)) excretion, which has been found to be elevated in patients presenting with high-altitude pulmonary edema (HAPE), precedes edema formation. Prospective studies in a total of 12 subjects with susceptibility to HAPE. In a chamber study, seven subjects susceptible to HAPE and five nonsusceptible control subjects were exposed for 24 h to an altitude of 450 m (control day), and exposed for 20 h to 4,000 m after slow decompression over 4 h. In a field study, prospective measurements at low and high altitude were performed in five subjects developing HAPE at 4,559 m. Mountaineers with a radiographically documented history of HAPE and control subjects who did not develop HAPE with identical high-altitude exposure. 24-h urine collections. In the hypobaric chamber, none of the subjects developed HAPE. The 24-h urinary LTE(4) did not differ between HAPE susceptible and control subjects, nor between hypoxia and normoxic control day. In the field study, urinary LTE(4) was not increased in subjects with HAPE compared to values obtained prior to HAPE at high altitude and during 2 control days at low altitude. These data do not provide evidence that cysteinyl-leukotriene-mediated inflammatory response is associated with HAPE susceptibility or the development of HAPE within the context of our studies.

  4. A genome wide study of genetic adaptation to high altitude in feral Andean Horses of the páramo.

    PubMed

    Hendrickson, Sher L

    2013-12-17

    Life at high altitude results in physiological and metabolic challenges that put strong evolutionary pressure on performance due to oxidative stress, UV radiation and other factors dependent on the natural history of the species. To look for genes involved in altitude adaptation in a large herbivore, this study explored genome differentiation between a feral population of Andean horses introduced by the Spanish in the 1500s to the high Andes and their Iberian breed relatives. Using allelic genetic models and Fst analyses of ~50 K single nucleotide polymorphisms (SNPs) across the horse genome, 131 candidate genes for altitude adaptation were revealed (Bonferoni of p ≤ 2 × 10(-7)). Significant signals included the EPAS1 in the hypoxia-induction-pathway (HIF) that was previously discovered in human studies (p = 9.27 × 10(-8)); validating the approach and emphasizing the importance of this gene to hypoxia adaptation. Strong signals in the cytochrome P450 3A gene family (p = 1.5 ×10(-8)) indicate that other factors, such as highly endemic vegetation in altitude environments are also important in adaptation. Signals in tenuerin 2 (TENM2, p = 7.9 × 10(-14)) along with several other genes in the nervous system (gene categories representation p = 5.1 × 10(-5)) indicate the nervous system is important in altitude adaptation. In this study of a large introduced herbivore, it becomes apparent that some gene pathways, such as the HIF pathway are universally important for high altitude adaptation in mammals, but several others may be selected upon based on the natural history of a species and the unique ecology of the altitude environment.

  5. Hypoxia awareness training for aircrew: a comparison of two techniques.

    PubMed

    Singh, Bhupinder; Cable, Gordon G; Hampson, Greg V; Pascoe, Glenn D; Corbett, Mark; Smith, Adrian

    2010-09-01

    Major hazards associated with hypoxia awareness training are the risks of decompression sickness, barotrauma, and loss of consciousness. An alternate method has been developed which combines exposure to a simulated altitude of 10,000 ft (3048 m) with breathing of a gas mixture containing 10% oxygen and 90% nitrogen. The paradigm, called Combined Altitude and Depleted Oxygen (CADO), places the subjects at a physiological altitude of 25,000 ft (7620 m) and provides demonstration of symptoms of hypoxia and the effects of pressure change. CADO is theoretically safer than traditional training at a simulated altitude of 25,000 ft (7620 m) due to a much lower risk of decompression sickness (DCS) and has greater fidelity of training for fast jet aircrew (mask-on hypoxia). This study was conducted to validate CADO by comparing it with hypobaric hypoxia. There were 43 subjects who were exposed to two regimens of hypoxia training: hypobaric hypoxia (HH) at a simulated altitude of 25,000 ft (7620 m) and CADO. Subjective, physiological, and performance data of the subjects were collected, analyzed, and compared. There were no significant differences in the frequency and severity of the 24 commonly reported symptoms, or in the physiological response, between the two types of hypoxia exposure. CADO is similar to HH in terms of the type and severity of symptoms experienced by subjects, and appears to be an effective, useful, and safe tool for hypoxia training.

  6. Altitude-dependent changes of directional hearing in mountaineers.

    PubMed Central

    Rosenberg, M E; Pollard, A J

    1992-01-01

    This study demonstrates apparent deterioration in the ability to localize sound associated with acute exposure to high altitude in ten subjects on three mountaineering expeditions. Furthermore, the auditory localization errors improved to sea level values after a period of acclimatization. Occurring at altitudes where overt neurological symptoms are not usually seen, impairment of sensory perception may explain the increase in accidental deaths associated with altitude exposure due to disorientation and misjudgment but before hypoxia is evident. PMID:1422652

  7. Metabolomic analysis of anti-hypoxia and anti-anxiety effects of Fu Fang Jin Jing Oral Liquid.

    PubMed

    Liu, Xia; Zhu, Wei; Guan, Shuhong; Feng, Ruihong; Zhang, Hui; Liu, Qiuhong; Sun, Peng; Lin, Donghai; Zhang, Naixia; Shen, Jun

    2013-01-01

    Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as

  8. Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins

    PubMed Central

    Parraguez, Victor H.; Mamani, Sandra; Cofré, Eileen; Castellaro, Giorgio; Urquieta, Bessie; De los Reyes, Mónica; Astiz, Susana; Gonzalez-Bulnes, Antonio

    2015-01-01

    Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well-characterized sheep-model, we aimed to determine whether long- and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long- and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage. PMID:26560325

  9. Circadian and Sex Differences After Acute High-Altitude Exposure: Are Early Acclimation Responses Improved by Blue Light?

    PubMed

    Silva-Urra, Juan A; Núñez-Espinosa, Cristian A; Niño-Mendez, Oscar A; Gaitán-Peñas, Héctor; Altavilla, Cesare; Toro-Salinas, Andrés; Torrella, Joan R; Pagès, Teresa; Javierre, Casimiro F; Behn, Claus; Viscor, Ginés

    2015-12-01

    The possible effects of blue light during acute hypoxia and the circadian rhythm on several physiological and cognitive parameters were studied. Fifty-seven volunteers were randomly assigned to 2 groups: nocturnal (2200-0230 hours) or diurnal (0900-1330 hours) and exposed to acute hypoxia (4000 m simulated altitude) in a hypobaric chamber. The participants were illuminated by blue LEDs or common artificial light on 2 different days. During each session, arterial oxygen saturation (Spo2), blood pressure, heart rate variability, and cognitive parameters were measured at sea level, after reaching the simulated altitude of 4000 m, and after 3 hours at this altitude. The circadian rhythm caused significant differences in blood pressure and heart rate variability. A 4% to 9% decrease in waking nocturnal Spo2 under acute hypoxia was observed. Acute hypoxia also induced a significant reduction (4%-8%) in systolic pressure, slightly more marked (up to 13%) under blue lighting. Women had significantly increased systolic (4%) and diastolic (12%) pressures under acute hypoxia at night compared with daytime pressure; this was not observed in men. Some tendencies toward better cognitive performance (d2 attention test) were seen under blue illumination, although when considered together with physiological parameters and reaction time, there was no conclusive favorable effect of blue light on cognitive fatigue suppression after 3 hours of acute hypobaric hypoxia. It remains to be seen whether longer exposure to blue light under hypobaric hypoxic conditions would induce favorable effects against fatigue. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  10. [Correlation between EGLN1 gene, protein express in lung tissue of rats and pulmonary artery pressure at different altitude].

    PubMed

    Li, S H; Li, S; Sun, L; Bai, Z Z; Yang, Q Y; Ga, Q; Jin, G E

    2016-08-23

    To investigate the correlation between pulmonary artery pressure (PAP) and the expression level of Egl nine homologue 1 (EGLN1) gene or its protein in lung tissue of rats at different altitudes. Totally 121 male Wistar rats were randomly divided into low altitude group (n=11), moderate altitude group and high altitude group, the rats in moderate altitude and high altitude group were further divided into 1(st) day, 3(rd) days, 7(th) days, 15(th) day and 30(th) day group according to the exposure time to hypoxic environment, each group 11 rats. The low altitude group, the PAP of rats were determined by physiological signal acquisition system, and tissue samples were collected in liquid nitrogen container for storage at an altitude of 498 m area. Moderate altitude group rats were placed in altitude of 2 260 meters of natural environment, 5 high altitude groups rats were placed in the hypobaric hypoxic chamber, simulating altitude of 4 500 meters. The PAP of rats in moderate altitude group and high altitude group were also determined by physiological signal acquisition system, and tissue samples were collected when rats were exposed to hypoxia at 1(st), 3(rd), 7(th), 15(th) and 30(th) day; Western blot was used to determine expression levels of EGLN1 protein, and person correlation analysis was used to analyze whether the protein was related to the formation of pulmonary arterial hypertension (PH) under hypoxia. Real-time quantitive PCR method determined expression levels of EGLN1 mRNA in lung tissues, and the relative expression method was used to analyze PCR data, and finally assess whether the EGLN1 gene was the initial cause of the formation of PH during hypoxia. The mean PAP of rats was (20.0±3.2) mmHg (1 mmHg=0.133 kPa) in low altitude group; in moderate altitude group, mean PAP began to increase slightly when rats were exposed to hypoxia on the 15(th) day and reached at (22.7±4.1) mmHg on hypoxic 30(th) day, but compared with the low altitude group, there was

  11. Submaximal Exercise and Cognitive Function Testing at Altitude to Determine the Impact of Different Levels of Hypobaric Hypoxia

    DTIC Science & Technology

    1997-01-01

    would exercise and two who were controls). The control included either playing bingo or remaining inactive. The tests were administered again after...15 added benefits may be outweighed by muscle fatigue (Tomporowski & Ellis, 1986). Altitude and Exercise Performance The interplay among hypoxia...an inevitable part of aviation. With the benefits and convenience of ascending into the sky 35 in an aircraft, come the risks of operating in what

  12. Domain Specific Changes in Cognition at High Altitude and Its Correlation with Hyperhomocysteinemia

    PubMed Central

    Sharma, Vijay K.; Das, Saroj K.; Dhar, Priyanka; Hota, Kalpana B.; Mahapatra, Bidhu B.; Vashishtha, Vivek; Kumar, Ashish; Hota, Sunil K.; Norboo, Tsering; Srivastava, Ravi B.

    2014-01-01

    Though acute exposure to hypobaric hypoxia is reported to impair cognitive performance, the effects of prolonged exposure on different cognitive domains have been less studied. The present study aimed at investigating the time dependent changes in cognitive performance on prolonged stay at high altitude and its correlation with electroencephalogram (EEG) and plasma homocysteine. The study was conducted on 761 male volunteers of 25–35 years age who had never been to high altitude and baseline data pertaining to domain specific cognitive performance, EEG and homocysteine was acquired at altitude ≤240 m mean sea level (MSL). The volunteers were inducted to an altitude of 4200–4600 m MSL and longitudinal follow-ups were conducted at durations of 03, 12 and 18 months. Neuropsychological assessment was performed for mild cognitive impairment (MCI), attention, information processing rate, visuo-spatial cognition and executive functioning. Total homocysteine (tHcy), vitamin B12 and folic acid were estimated. Mini Mental State Examination (MMSE) showed temporal increase in the percentage prevalence of MCI from 8.17% on 03 months of stay at high altitude to 18.54% on 18 months of stay. Impairment in visuo-spatial executive, attention, delayed recall and procedural memory related cognitive domains were detected following prolonged stay in high altitude. Increase in alpha wave amplitude in the T3, T4 and C3 regions was observed during the follow-ups which was inversely correlated (r = −0.68) to MMSE scores. The tHcy increased proportionately with duration of stay at high altitude and was correlated with MCI. No change in vitamin B12 and folic acid was observed. Our findings suggest that cognitive impairment is progressively associated with duration of stay at high altitude and is correlated with elevated tHcy in the plasma. Moreover, progressive MCI at high altitude occurs despite acclimatization and is independent of vitamin B12 and folic acid. PMID:24988417

  13. In-flight hypoxia incidents in military aircraft: causes and implications for training.

    PubMed

    Cable, Gordon G

    2003-02-01

    expectation may be that it is only a problem of high altitude. Proper fitting of masks, leak checks, and equipment checks should be taught to all aircrew and reinforced regularly. Current hypobaric chamber training methods should be reviewed for relevance to the most at-risk aircrew population. Methods that can simulate subtle incapacitation while wearing oxygen equipment should be explored. Hypoxia in flight still remains a serious threat to aviators, and can result in fatalities.

  14. High-Altitude Illness

    MedlinePlus

    ... after you travel. Make sure you pack enough water while you are active. Avoid or limit the amount of alcohol you consume. High-altitude illness treatment It is important to treat high-altitude illness ...

  15. Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction.

    PubMed

    Barnholt, Kimberly E; Hoffman, Andrew R; Rock, Paul B; Muza, Stephen R; Fulco, Charles S; Braun, Barry; Holloway, Leah; Mazzeo, Robert S; Cymerman, Allen; Friedlander, Anne L

    2006-06-01

    High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

  16. Oxygen enrichment and its application to life support systems for workers in high-altitude areas

    PubMed Central

    Li, Yongling; Liu, Yingshu

    2014-01-01

    Background: Workers coming from lowland regions are at risk of developing acute mountain sickness (AMS) when working in low oxygen high-altitude areas. Objectives: The aim of this study was to improve the conditions that lead to hypoxia and ensure the safety of the high-altitude workers. We analyzed the influence of low atmospheric pressure on the oxygen enrichment process in high-altitude areas using an engineering method called low-pressure swing adsorption (LPSA). Methods: Fourteen male subjects were screened and divided into three groups by type of oxygen supply system used: (1) oxygen cylinder group; (2) LPSA oxygen dispersal group; and (3) control group. These tests included arterial oxygen saturation (SaO2), pulse rate (PR), breaths per minute (BPM), and blood pressure (BP). Results: The results showed that after supplying oxygen using the LPSA method at the tunnel face, the SaO2 of workers increased; the incidence of acute mountain sickness, PR, and BPM significantly decreased. Conclusions: The LPSA life support system was found to be a simple, convenient, efficient, reliable, and applicable approach to ensure proper working conditions at construction sites in high-altitude areas. PMID:25000108

  17. Heart rate and cardiovascular variability at high altitude.

    PubMed

    Bernardi, Luciano

    2007-01-01

    Primary effect of hypobaric hypoxia on the circulation is a direct vasodilatory effect on the peripheral circulation, which is normally prevented by a sympathetic-induced vasoconstriction. Most of the clinical methods for testing the baroreflex sensitivity only evaluate the cardiac-vagal branch of the baroreflex, but at altitude it is also of importance to test the vascular effects of the baroreflex. This is possible by directly measuring sympathetic efferent activity (by microneurography) or by directly stimulating the carotid baroreceptors (by the neck suction). By cyclical stimulation of the carotid baroreceptors, neck suction-synchronous reflex oscillations could be observed in a large number of signals, including RR interval, blood pressure, microcirculation, muscle sympathetic nerve activity. An increase in fluctuations at the same frequency of the stimulus was considered an evidence of the ability of the carotid baroreceptors to modulate a given physiological signal. The sinusoidal neck suction was set at 0.10 Hz (low-frequency stimulation), or to a frequency close to- but distinct from- the respiratory signal (0.20 Hz, high frequency stimulation, whereas respiration was fixed to 0.25 Hz). The method is noninvasive, without side effects connected to use of drugs, and evaluates both the response to the heart and to the blood pressure of the baroreflex. The altitude-induced sympathetic activation was evidenced in sea level natives by a decrease in RR interval, an increase in blood pressure and in the 0.1Hz components of cardiac and vascular signals. The arterial baroflex was active on RR interval and also in blood pressure, even during acute exposure to high altitude, thus indicating that it was counteracting and modulating the increase in sympathetic tone. Signs of exaggerated sympathetic activation were evident in subjects with severe acute mountain sickness, while successful therapy was associated with a restoration of autonomic modulation. Conversely

  18. Improvement of myocardial perfusion in coronary patients after intermittent hypobaric hypoxia.

    PubMed

    del Pilar Valle, Maria; García-Godos, Félix; Woolcott, Orison O; Marticorena, José M; Rodríguez, Víctor; Gutiérrez, Isabel; Fernández-Dávila, Luis; Contreras, Abel; Valdivia, Luis; Robles, Juan; Marticorena, Emilio A

    2006-01-01

    Persons living at high altitude (exposed to hypoxia) have a greater number of coronary and peripheral branches in the heart than persons living at sea level. In this study we investigated the effect of intermittent hypobaric hypoxia on myocardial perfusion in patients with coronary heart disease. We studied 6 male patients (aged>or=53 years) with severe stable coronary heart disease. All patients were born at sea level and lived in that environment. They underwent 14 sessions of exposure to intermittent hypobaric hypoxia (equivalent to a simulated altitude of 4200 m). Myocardial perfusion was assessed at baseline and after treatment with hypoxia by use of exercise perfusion imaging with technetium 99m sestamibi. After the sessions of hypoxia, myocardial perfusion was significantly improved. The summed stress score for hypoperfusion, in arbitrary units, decreased from 9.5+ to 4.5+ after treatment (P=.036). There was no evidence of impairment of myocardial perfusion in any patient after treatment. Intermittent hypobaric hypoxia improved myocardial perfusion in patients with severe coronary heart disease. Though preliminary, our results suggest that exposure to intermittent hypobaric hypoxia could be an alternative for the management of patients with chronic coronary heart disease.

  19. Operation Everest II. Altitude Decompression Sickness during Repeated Altitude Exposure,

    DTIC Science & Technology

    1986-05-01

    Bends, Altitude, Hypobaric Chamber ILrJ " . .. . . " --" . .. " * .- . - - ’,, 3 INTRODUCTION Altitude Decompression Sickness (ADS) is a well...recognized and serious consequence of exposure to hypobaric conditions. It has been described during and after aircraft as well as hypobaric chamber flights...was noted in investigators during a recent study of chronic progressive hypoxia in a hypobaric chamber entitled Operation Everest II. The observations

  20. Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice.

    PubMed

    Qiao, Yanxiang; Liu, Zhenfang; Yan, Xianliang; Luo, Chuanming

    2015-04-01

    Intermittent hypoxia was a simulation of a high-altitude environment. Neuro-inflammation post brain ischemia was considered as a vital impact which contributed to cognitive-functional deficit. The isoform of nitric oxide synthase (iNOS) was an inflammation factor secreted by microglias in neuro-inflammation. In this study, we established a high-altitude environment as the hypoxic condition. Twenty mice were selected and randomized into a hypoxia group (n = 10) or a normoxia group (n = 10) post three vessel occlusion-induced brain ischemia. An enhancement of cognitive-functional recovery was presented in the hypoxia group by survival neuron counting and revealed by the Morris water maze test. Meanwhile, a high level of hypoxia-inducable factor 1 (HIF-1) expression associated with a lower expression of iNOS was observed in the border between infarcts and normal tissue of the hippocampus in the hypoxia group. However, these phenomenons were blocked by HIF-1 inhibition. This suggested that the acceleration of cognitive-functional recovery induced by intermittent hypoxia may depend on HIF-1 activating. An imitation of the hypoxic condition with or without HIF-1 inhibition was operated on the BV-2 cell. A high level of HIF-1 expression associated with a lower-level expression of iNOS was performed in the hypoxic condition. These data suggested that intermittent hypoxia can accelerate cognitive function recovery through attenuating neuro-inflammation.

  1. Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Wessel, J. H., III

    2011-01-01

    INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 < 0.209 at or near sea level pressure to match the ambient O2 partial pressure (iso-pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

  2. Acclimatization to long-term hypoxia: gene expression in ovine carotid arteries

    PubMed Central

    Goyal, Ravi

    2014-01-01

    Exposure to acute high-altitude hypoxia is associated with an increase in cerebral blood flow (CBF) as a consequence of low arterial O2 tension. However, in response to high altitude acclimatization, CBF returns to levels similar to those at sea level, and tissue blood flow is maintained by an increase in angiogenesis. Of consequence, dysregulation of the acclimatization responses and CBF can result in acute mountain sickness, acute cerebral and/or pulmonary edema. To elucidate the signal transduction pathways involved in successful acclimatization to high altitude, in ovine carotid arteries, we tested the hypothesis that high altitude-associated long-term hypoxia results in changes in gene expression of critical signaling pathways. We acclimatized nonpregnant adult sheep to 3,801 m altitude for ∼110 days and conducted oligonucleotide microarray experiments on carotid arteries. Of a total of 116 regulated genes, 58 genes were significantly upregulated and 58 genes were significantly downregulated (each >2-fold, P < 0.05). Major upregulated genes included suprabasin and myelin basic protein, whereas downregulated genes included BAG2. Several of these genes are known to activate the ERK canonical signal transduction pathway and the process of angiogenesis. We conclude that among other changes, the altered signal transduction molecules involved in high-altitude acclimatization are associated ERK activation and angiogenesis. PMID:25052263

  3. Acclimatization to long-term hypoxia: gene expression in ovine carotid arteries.

    PubMed

    Goyal, Ravi; Longo, Lawrence D

    2014-10-01

    Exposure to acute high-altitude hypoxia is associated with an increase in cerebral blood flow (CBF) as a consequence of low arterial O2 tension. However, in response to high altitude acclimatization, CBF returns to levels similar to those at sea level, and tissue blood flow is maintained by an increase in angiogenesis. Of consequence, dysregulation of the acclimatization responses and CBF can result in acute mountain sickness, acute cerebral and/or pulmonary edema. To elucidate the signal transduction pathways involved in successful acclimatization to high altitude, in ovine carotid arteries, we tested the hypothesis that high altitude-associated long-term hypoxia results in changes in gene expression of critical signaling pathways. We acclimatized nonpregnant adult sheep to 3,801 m altitude for ∼110 days and conducted oligonucleotide microarray experiments on carotid arteries. Of a total of 116 regulated genes, 58 genes were significantly upregulated and 58 genes were significantly downregulated (each >2-fold, P < 0.05). Major upregulated genes included suprabasin and myelin basic protein, whereas downregulated genes included BAG2. Several of these genes are known to activate the ERK canonical signal transduction pathway and the process of angiogenesis. We conclude that among other changes, the altered signal transduction molecules involved in high-altitude acclimatization are associated ERK activation and angiogenesis. Copyright © 2014 the American Physiological Society.

  4. Short-term exposure to hypoxia for work and leisure activities in health and disease: which level of hypoxia is safe?

    PubMed

    Burtscher, Martin; Mairer, Klemens; Wille, Maria; Gatterer, Hannes; Ruedl, Gerhard; Faulhaber, Martin; Sumann, Günther

    2012-06-01

    Exposures to natural and simulated altitudes entail reduced oxygen availability and thus hypoxia. Depending on the level of hypoxia, the duration of exposure, the individual susceptibility, and preexisting diseases, health problems of variable severity may arise. Although millions of people are regularly or occasionally performing mountain sport activities, are transported by airplanes, and are more and more frequently exposed to short-term hypoxia in athletic training facilities or at their workplace, e.g., with fire control systems, there is no clear consensus on the level of hypoxia which is generally well tolerated by human beings when acutely exposed for short durations (hours to several days). Available data from peer-reviewed literature report adaptive responses even to altitudes below 2,000 m or corresponding normobaric hypoxia (F(i)O(2) > 16.4%), but they also suggest that most of exposed subjects without severe preexisting diseases can tolerate altitudes up to 3,000 m (F(i)O(2) > 14.5%) well. However, physical activity and unusual environmental conditions may increase the risk to get sick. Large interindividual variations of responses to hypoxia have to be expected, especially in persons with preexisting diseases. Thus, the assessment of those responses by hypoxic challenge testing may be helpful whenever possible.

  5. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth

    PubMed Central

    Julian, Colleen G.; Yang, Ivana V.; Browne, Vaughn A.; Vargas, Enrique; Rodriguez, Carmelo; Pedersen, Brent S.; Moore, Lorna G.; Schwartz, David A.

    2014-01-01

    Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.—Julian, C. G., Yang, I. V., Browne, V. A., Vargas, E., Rodriguez, C., Pedersen, B. S., Moore, L. G., Schwartz, D. A. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal

  6. Risk prediction score for severe high altitude illness: a cohort study.

    PubMed

    Canouï-Poitrine, Florence; Veerabudun, Kalaivani; Larmignat, Philippe; Letournel, Murielle; Bastuji-Garin, Sylvie; Richalet, Jean-Paul

    2014-01-01

    Risk prediction of acute mountain sickness, high altitude (HA) pulmonary or cerebral edema is currently based on clinical assessment. Our objective was to develop a risk prediction score of Severe High Altitude Illness (SHAI) combining clinical and physiological factors. Study population was 1017 sea-level subjects who performed a hypoxia exercise test before a stay at HA. The outcome was the occurrence of SHAI during HA exposure. Two scores were built, according to the presence (PRE, n = 537) or absence (ABS, n = 480) of previous experience at HA, using multivariate logistic regression. Calibration was evaluated by Hosmer-Lemeshow chisquare test and discrimination by Area Under ROC Curve (AUC) and Net Reclassification Index (NRI). The score was a linear combination of history of SHAI, ventilatory and cardiac response to hypoxia at exercise, speed of ascent, desaturation during hypoxic exercise, history of migraine, geographical location, female sex, age under 46 and regular physical activity. In the PRE/ABS groups, the score ranged from 0 to 12/10, a cut-off of 5/5.5 gave a sensitivity of 87%/87% and a specificity of 82%/73%. Adding physiological variables via the hypoxic exercise test improved the discrimination ability of the models: AUC increased by 7% to 0.91 (95%CI: 0.87-0.93) and 17% to 0.89 (95%CI: 0.85-0.91), NRI was 30% and 54% in the PRE and ABS groups respectively. A score computed with ten clinical, environmental and physiological factors accurately predicted the risk of SHAI in a large cohort of sea-level residents visiting HA regions.

  7. Chronic stress of rainbow trout Oncorhynchus mykiss at high altitude: a field study.

    PubMed

    Hunt von Herbing, I; Pan, T-C F; Méndez-Sánchez, F; Garduño-Paz, M; Hernández-Gallegos, O; Ruiz-Gómez, M L; Rodríguez-Vargas, G

    2015-07-01

    The stress response of Oncorhynchus mykiss in high-altitude farms in central Mexico was investigated over two seasons: the cool (9·1-13·7° C) dry winter season, and the warmer (14·7-15·9° C), wetter summer season. Fish were subjected to an acute stress test followed by sampling of six physiological variables: blood cortisol, glucose, lactate, total antioxidant capacity, haemoglobin concentration and per cent packed cell volume (VPC %). Multivariate analyses revealed that lactate and total antioxidant capacity were significantly higher in the summer, when water temperatures were warmer and moderate hypoxia (4·9-5·3 mg l(-1) ) prevailed. In contrast, plasma cortisol was significantly higher in the winter (mean ± s.e.: 76·7 ± 4·0 ng ml(-1) ) when temperatures were cooler and dissolved oxygen levels higher (6·05-7·9 mg l(-1) ), than in the summer (22·7 ± 3·8 ng ml(-1) ). Haemoglobin concentrations (mg dl(-1) ) were not significantly different between seasons, but VPC % was significantly higher in the summer (50%) than in the winter (35%). These results suggest that in summer, effects of high altitude on farmed fish are exacerbated by stresses of high temperatures and hypoxia, resulting in higher blood lactate, increased total antioxidant capacity and elevated VPC % levels. © 2015 The Fisheries Society of the British Isles.

  8. High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb.

    PubMed

    Hoffmann, Angelika; Kunze, Reiner; Helluy, Xavier; Milford, David; Heiland, Sabine; Bendszus, Martin; Pham, Mirko; Marti, Hugo H

    2016-01-01

    Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema.

  9. Response of skeletal muscle mitochondria to hypoxia.

    PubMed

    Hoppeler, Hans; Vogt, Michael; Weibel, Ewald R; Flück, Martin

    2003-01-01

    This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long-term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. Oxidative muscle metabolism is shifted towards a higher reliance on carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced. Moreover, in muscle cells of mountaineers returning from the Himalayas, we find accumulations of lipofuscin, believed to be a mitochondrial degradation product. Low mitochondrial contents are also observed in high-altitude natives such as Sherpas. In these subjects high-altitude performance seems to be improved by better coupling between ATP demand and supply pathways as well as better metabolite homeostasis. The hypoxia-inducible factor 1 (HIF-1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). HIF-1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF-1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF-1a. A further mechanism that seems implicated in the hypoxia response of muscle mitochondria is related to the formation of reactive oxygen species (ROS) in mitochondria during oxidative phosphorylation. How exactly ROS interfere with HIF-1a as well as MAP kinase and other signalling pathways is debated. The current evidence suggests that mitochondria themselves could be important players in oxygen sensing.

  10. Normobaric hypoxia overnight impairs cognitive reaction time.

    PubMed

    Pramsohler, Stephan; Wimmer, Stefan; Kopp, Martin; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Martin; Netzer, Nikolaus Cristoph

    2017-05-15

    Impaired reaction time in patients suffering from hypoxia during sleep, caused by sleep breathing disorders, is a well-described phenomenon. High altitude sleep is known to induce periodic breathing with central apneas and oxygen desaturations, even in perfectly healthy subjects. However, deficits in reaction time in mountaineers or workers after just some nights of hypoxia exposure are not sufficiently explored. Therefore, we aimed to investigate the impact of sleep in a normobaric hypoxic environment on reaction time divided by its cognitive and motoric components. Eleven healthy non acclimatized students (5f, 6m, 21 ± 2.1 years) slept one night at a simulated altitude of 3500 m in a normobaric hypoxic room, followed by a night with polysomnography at simulated 5500 m. Preexisting sleep disorders were excluded via BERLIN questionnaire. All subjects performed a choice reaction test (SCHUHFRIED RT, S3) at 450 m and directly after the nights at simulated 3500 and 5500 m. We found a significant increase of cognitive reaction time with higher altitude (p = 0.026). No changes were detected in movement time (p = n.s.). Reaction time, the combined parameter of cognitive- and motoric reaction time, didn't change either (p = n.s.). Lower SpO 2 surprisingly correlated significantly with shorter cognitive reaction time (r = 0.78, p = 0.004). Sleep stage distribution and arousals at 5500 m didn't correlate with reaction time, cognitive reaction time or movement time. Sleep in hypoxia does not seem to affect reaction time to simple tasks. The component of cognitive reaction time is increasingly delayed whereas motoric reaction time seems not to be affected. Low SpO 2 and arousals are not related to increased cognitive reaction time therefore the causality remains unclear. The fact of increased cognitive reaction time after sleep in hypoxia, considering high altitude workers and mountaineering operations with overnight stays, should be further investigated.

  11. Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid

    PubMed Central

    Guan, Shuhong; Feng, Ruihong; Zhang, Hui; Liu, Qiuhong; Sun, Peng; Lin, Donghai; Zhang, Naixia; Shen, Jun

    2013-01-01

    Background Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. Methods In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. Results Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. Conclusions FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the

  12. Widespread Signals of Convergent Adaptation to High Altitude in Asia and America

    PubMed Central

    Foll, Matthieu; Gaggiotti, Oscar E.; Daub, Josephine T.; Vatsiou, Alexandra; Excoffier, Laurent

    2014-01-01

    Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in different continents has accumulated. This lack of evidence can be due to truly different evolutionary responses, but it can also be due to the low power of former studies that have mainly focused on populations from a single geographical region or performed separate analyses on multiple pairs of populations to avoid problems linked to shared histories between some populations. We introduce here a hierarchical Bayesian method to detect local adaptation that can deal with complex demographic histories. Our method can identify selection occurring at different scales, as well as convergent adaptation in different regions. We apply our approach to the analysis of a large SNP data set from low- and high-altitude human populations from America and Asia. The simultaneous analysis of these two geographic areas allows us to identify several candidate genome regions for altitudinal selection, and we show that convergent evolution among continents has been quite common. In addition to identifying several genes and biological processes involved in high-altitude adaptation, we identify two specific biological pathways that could have evolved in both continents to counter toxic effects induced by hypoxia. PMID:25262650

  13. Dose-response of altitude training: how much altitude is enough?

    PubMed

    Levine, Benjamin D; Stray-Gundersen, James

    2006-01-01

    Altitude training continues to be a key adjunctive aid for the training of competitive athletes throughout the world. Over the past decade, evidence has accumulated from many groups of investigators that the "living high--training low" approach to altitude training provides the most robust and reliable performance enhancements. The success of this strategy depends on two key features: 1) living high enough, for enough hours per day, for a long enough period of time, to initiate and sustain an erythropoietic effect of high altitude; and 2) training low enough to allow maximal quality of high intensity workouts, requiring high rates of sustained oxidative flux. Because of the relatively limited access to environments where such a strategy can be practically applied, numerous devices have been developed to "bring the mountain to the athlete," which has raised the key issue of the appropriate "dose" of altitude required to stimulate an acclimatization response and performance enhancement. These include devices using molecular sieve technology to provide a normobaric hypoxic living or sleeping environment, approaches using very high altitudes (5,500m) for shorter periods of time during the day, and "intermittent hypoxic training" involving breathing very hypoxic gas mixtures for alternating 5 minutes periods over the course of 60-90 minutes. Unfortunately, objective testing of the strategies employing short term (less than 4 hours) normobaric or hypobaric hypoxia has failed to demonstrate an advantage of these techniques. Moreover individual variability of the response to even the best of living high--training low strategies has been great, and the mechanisms behind this variability remain obscure. Future research efforts will need to focus on defining the optimal dosing strategy for these devices, and determining the underlying mechanisms of the individual variability so as to enable the individualized "prescription" of altitude exposure to optimize the performance of

  14. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives

    PubMed Central

    Lundby, Carsten; Sander, Mikael; van Hall, Gerrit; Saltin, Bengt; Calbet, José A L

    2006-01-01

    The tight relation between arterial oxygen content and maximum oxygen uptake () within a given person at sea level is diminished with altitude acclimatization. An explanation often suggested for this mismatch is impairment of the muscle O2 extraction capacity with chronic hypoxia, and is the focus of the present study. We have studied six lowlanders during maximal exercise at sea level (SL) and with acute (AH) exposure to 4100 m altitude, and again after 2 (W2) and 8 weeks (W8) of altitude sojourn, where also eight high altitude native (Nat) Aymaras were studied. Fractional arterial muscle O2 extraction at maximal exercise was 90.0 ± 1.0% in the Danish lowlanders at sea level, and remained close to this value in all situations. In contrast to this, fractional arterial O2 extraction was 83.2 ± 2.8% in the high altitude natives, and did not change with the induction of normoxia. The capillary oxygen conductance of the lower extremity, a measure of oxygen diffusing capacity, was decreased in the Danish lowlanders after 8 weeks of acclimatization, but was still higher than the value obtained from the high altitude natives. The values were (in ml min−1 mmHg−1) 55.2 ± 3.7 (SL), 48.0 ± 1.7 (W2), 37.8 ± 0.4 (W8) and 27.7 ± 1.5 (Nat). However, when correcting oxygen conductance for the observed reduction in maximal leg blood flow with acclimatization the effect diminished. When calculating a hypothetical leg at altitude using either the leg blood flow or the O2 conductance values obtained at sea level, the former values were almost completely restored to sea level values. This would suggest that the major determinant for not to increase with acclimatization is the observed reduction in maximal leg blood flow and O2 conductance. PMID:16581864

  15. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

  16. AltitudeOmics: on the consequences of high-altitude acclimatization for the development of fatigue during locomotor exercise in humans

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Subudhi, Andrew W.; Lovering, Andrew T.; Roach, Robert C.

    2013-01-01

    The development of muscle fatigue is oxygen (O2)-delivery sensitive [arterial O2 content (CaO2) × limb blood flow (QL)]. Locomotor exercise in acute hypoxia (AH) is, compared with sea level (SL), associated with reduced CaO2 and exaggerated inspiratory muscle work (Winsp), which impairs QL, both of which exacerbate fatigue individually by compromising O2 delivery. Since chronic hypoxia (CH) normalizes CaO2 but exacerbates Winsp, we investigated the consequences of a 14-day exposure to high altitude on exercise-induced locomotor muscle fatigue. Eight subjects performed the identical constant-load cycling exercise (138 ± 14 W; 11 ± 1 min) at SL (partial pressure of inspired O2, 147.1 ± 0.5 Torr), in AH (73.8 ± 0.2 Torr), and in CH (75.7 ± 0.1 Torr). Peripheral fatigue was expressed as pre- to postexercise percent reduction in electrically evoked potentiated quadriceps twitch force (ΔQtw,pot). Central fatigue was expressed as the exercise-induced percent decrease in voluntary muscle activation (ΔVA). Resting CaO2 at SL and CH was similar, but CaO2 in AH was lower compared with SL and CH (17.3 ± 0.5, 19.3 ± 0.7, 20.3 ± 1.3 ml O2/dl, respectively). Winsp during exercise increased with acclimatization (SL: 387 ± 36, AH: 503 ± 53, CH: 608 ± 67 cmH2O·s−1·min−1; P < 0.01). Exercise at SL did not induce central or peripheral fatigue. ΔQtw,pot was significant but similar in AH and CH (21 ± 2% and 19 ± 3%; P = 0.24). ΔVA was significant in both hypoxic conditions but smaller in CH vs. AH (4 ± 1% vs. 8 ± 2%; P < 0.05). In conclusion, acclimatization to severe altitude does not attenuate the substantial impact of hypoxia on the development of peripheral fatigue. In contrast, acclimatization attenuates, but does not eliminate, the exacerbation of central fatigue associated with exercise in severe AH. PMID:23813531

  17. AltitudeOmics: on the consequences of high-altitude acclimatization for the development of fatigue during locomotor exercise in humans.

    PubMed

    Amann, Markus; Goodall, Stuart; Twomey, Rosie; Subudhi, Andrew W; Lovering, Andrew T; Roach, Robert C

    2013-09-01

    The development of muscle fatigue is oxygen (O2)-delivery sensitive [arterial O2 content (CaO2) × limb blood flow (QL)]. Locomotor exercise in acute hypoxia (AH) is, compared with sea level (SL), associated with reduced CaO2 and exaggerated inspiratory muscle work (Winsp), which impairs QL, both of which exacerbate fatigue individually by compromising O2 delivery. Since chronic hypoxia (CH) normalizes CaO2 but exacerbates Winsp, we investigated the consequences of a 14-day exposure to high altitude on exercise-induced locomotor muscle fatigue. Eight subjects performed the identical constant-load cycling exercise (138 ± 14 W; 11 ± 1 min) at SL (partial pressure of inspired O2, 147.1 ± 0.5 Torr), in AH (73.8 ± 0.2 Torr), and in CH (75.7 ± 0.1 Torr). Peripheral fatigue was expressed as pre- to postexercise percent reduction in electrically evoked potentiated quadriceps twitch force (ΔQtw,pot). Central fatigue was expressed as the exercise-induced percent decrease in voluntary muscle activation (ΔVA). Resting CaO2 at SL and CH was similar, but CaO2 in AH was lower compared with SL and CH (17.3 ± 0.5, 19.3 ± 0.7, 20.3 ± 1.3 ml O2/dl, respectively). Winsp during exercise increased with acclimatization (SL: 387 ± 36, AH: 503 ± 53, CH: 608 ± 67 cmH2O·s(-1)·min(-1); P < 0.01). Exercise at SL did not induce central or peripheral fatigue. ΔQtw,pot was significant but similar in AH and CH (21 ± 2% and 19 ± 3%; P = 0.24). ΔVA was significant in both hypoxic conditions but smaller in CH vs. AH (4 ± 1% vs. 8 ± 2%; P < 0.05). In conclusion, acclimatization to severe altitude does not attenuate the substantial impact of hypoxia on the development of peripheral fatigue. In contrast, acclimatization attenuates, but does not eliminate, the exacerbation of central fatigue associated with exercise in severe AH.

  18. A Mountain or a Plateau? Hematological Traits Vary Nonlinearly with Altitude in a Highland Lizard.

    PubMed

    González-Morales, Juan Carlos; Beamonte-Barrientos, Rene; Bastiaans, Elizabeth; Guevara-Fiore, Palestina; Quintana, Erendira; Fajardo, Victor

    High-altitude organisms exhibit hematological adaptations to augment blood transport of oxygen. One common mechanism is through increased values of blood traits such as erythrocyte count, hematocrit, and hemoglobin concentration. However, a positive relationship between altitude and blood traits is not observed in all high-altitude systems. To understand how organisms adapt to high altitudes, it is important to document physiological patterns related to hypoxia gradients from a greater variety of species. Here, we present an extensive hematological description for three populations of Sceloporus grammicus living at 2,500, 3,400, and 4,300 m. We did not find a linear increase with altitude for any of the blood traits we measured. Instead, we found nonlinear relationships between altitude and the blood traits erythrocyte number, erythrocyte size, hematocrit, and hemoglobin concentration. Erythrocyte number and hematocrit leveled off as altitude increased, whereas hemoglobin concentration and erythrocyte size were highest at intermediate altitude. Additionally, lizards from our three study populations are similar in blood pH, serum electrolytes, glucose, and lactate. Given that the highest-altitude population did not show the highest levels of the variables we measured, we suggest these lizards may be using different adaptations to cope with hypoxia than lizards at low or intermediate altitudes. We discuss future directions that research could take to investigate such potential adaptations.

  19. Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre-conditioning.

    PubMed

    Hu, Shengli; Li, Fei; Luo, Haishui; Xia, Yongzhi; Zhang, Jiuquan; Hu, Rong; Cui, Gaoyu; Meng, Hui; Feng, Hua

    2010-03-01

    Hypobaric hypoxia at high altitude can lead to brain damage and pre-conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain injury. This study investigates the effects of high altitude on traumatic brain injury (TBI) and examines the neuroprotection provided by HBO preconditioning against TBI. Rats were randomly divided into four groups: HBO pre-conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control group (PC, n=10) and plain sham operation group (sham, n=10). All groups were subjected to head trauma by weight drop device except for the sham group. Rats from each group were examined for neurological function, regional cerebral blood flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for analysis by transmission electron microscope. The score of neurological deficits in the HA group was highest, followed by the HBOP group and the PC group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain morphology and structure seen via the transmission electron microscope was diminished in the HA group, while fewer pathological injuries occurred in the HBOP and PC groups. High altitude aggravates TBI significantly and HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling to high altitude locations.

  20. High Altitude Medical Problems

    PubMed Central

    Hultgren, Herbert N.

    1979-01-01

    Increased travel to high altitude areas by mountaineers and nonclimbing tourists has emphasized the clinical problems associated with rapid ascent. Acute mountain sickness affects most sojourners at elevations above 10,000 feet. Symptoms are usually worse on the second or third day after arrival. Gradual ascent, spending one to three days at an intermediate altitude, and the use of acetazolamide (Diamox) will prevent or ameliorate symptoms in most instances. Serious and potentially fatal problems, such as high altitude pulmonary edema or cerebral edema, occur in approximately 0.5 percent to 1.0 percent of visitors to elevations above 10,000 feet—especially with heavy physical exertion on arrival, such as climbing or skiing. Early recognition, high flow oxygen therapy and prompt descent are crucially important in management. Our knowledge of the causes of these and other high altitude problems, such as retinal hemorrhage, systemic edema and pulmonary hypertension, is still incomplete. Even less is known of the effect of high altitudes on medical conditions common at sea level or on the action of commonly used drugs. ImagesFigure 2. PMID:483805

  1. Normobaric Hypoxia Effects on Balance Measured by Computerized Dynamic Posturography.

    PubMed

    Wagner, Dale R; Saunders, Skyler; Robertson, Brady; Davis, John E

    2016-09-01

    Wagner, Dale R., Skyler Saunders, Brady Robertson, and John E. Davis. Normobaric hypoxia effects on balance measured by computerized dynamic posturography. High Alt Med Biol. 17:222-227, 2016.-Background/Aim: Equilibrium was measured by computerized dynamic posturography at varying levels of normobaric hypoxia before and after exercise. Following a familiarization trial, 12 males (27.3 ± 7.1 years) completed three sessions in random order on a NeuroCom SMART Balance Master: a sham trial at the ambient altitude of 1500 m and simulated altitudes of 3000 and 5000 m created by a hypoxic generator. The NeuroCom provided composite scores for a sensory organization test of equilibrium and a motor control test to assess the appropriate motor response. Additional information on somatosensory, visual, and vestibular responses was obtained. Each session consisted of 20 minutes of rest followed by the NeuroCom test, then 10 minutes of exercise, and 10 minutes of recovery followed by a second NeuroCom test, all while connected to the hypoxic generator. Mean differences were identified with a two-way (pre/postexercise and altitude condition), repeated-measures analysis of variance. The composite sensory score was significantly lower (p < 0.001) during the 5000 m trial (73.4 ± 12.0) compared to the 1500 m (80.8 ± 7.0) and 3000 m (84.1 ± 5.0) altitudes. The inability to ignore inaccurate visual cues in a situation of visual conflict was the most common sensory error. Motor control was not affected by altitude or exercise. These results suggest that moderate hypoxia does not affect balance, but severe hypoxia significantly reduces equilibrium. Furthermore, it appears that the alterations in equilibrium are primarily from impairments in visual function.

  2. Periodic breathing and oxygen supplementation in Chilean miners at high altitude (4200m).

    PubMed

    Moraga, Fernando A; Jiménez, Daniel; Richalet, Jean Paul; Vargas, Manuel; Osorio, Jorge

    2014-11-01

    Our objective was to determine the nocturnal ventilatory pattern and characterize the effect of oxygen enrichment on nocturnal ventilatory pattern and sleep quality in miners exposed to intermittent hypobaric hypoxia at 4200m. A total of 16 acclimatized miners were studied. Nocturnal ventilatory pattern (plethysmographic inductance), arterial oxygen saturation and heart rate (pulse oximetry) were performed in 9/16 subjects. Sleep quality at high altitude was assessed by self-questionnaires in 16/16 subjects. All measurements were performed during at least 7h of sleep. Subjects were studied while sleeping at high altitude without (control, C) and with oxygen supplementation (FiO2=0.25, treated, T). Periodic breathing (%) C: 25±18 vs T: 6.6±5.6 (p<0.05), apneas index (no./h) C: 34.9±24.1 vs T: 8.5±6.8 (p<0.05); and sleep quality C: 17.8±3.4 vs T: 12.1±2.2 (p<0.0001) were evaluated. In conclusion, periodic breathing with apneas was present in miners exposed to high altitude for 1 to 4 years and was reduced by treatment with supplementary oxygen. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Nutritional strategies for football: counteracting heat, cold, high altitude, and jet lag.

    PubMed

    Armstrong, Lawrence E

    2006-07-01

    Environmental factors often influence the physical and mental performance of football players. Heat, cold, high altitude, and travel across time zones (i.e. leading to jet lag) act as stressors that alter normal physiological function, homeostasis, metabolism, and whole-body nutrient balance. Rather than accepting performance decrements as inevitable, well-informed coaches and players should plan strategies for training and competition that offset environmental challenges. Considering the strength of scientific evidence, this paper reviews recommendations regarding nutritional interventions that purportedly counterbalance dehydration, hyperthermia, hypothermia, hypoxia, acute or chronic substrate deficiencies, sleep loss, and desynchronization of internal biological clocks.

  4. High-altitude headache: the effects of real vs sham oxygen administration.

    PubMed

    Benedetti, Fabrizio; Durando, Jennifer; Giudetti, Lucia; Pampallona, Alan; Vighetti, Sergio

    2015-11-01

    High-altitude, or hypobaric hypoxia, headache has recently emerged as an interesting model to study placebo and nocebo responses, and particularly their peripheral mechanisms. In this study, we analyze the response of this type of headache to either real or sham (placebo) oxygen (O(2)) administration at an altitude of 3500 m, where blood oxygen saturation (SO(2)) drops from the normal value of about 98% to about 85%. In a trial in which a double-blind administration of either 100% O(2) or sham O(2) was administered, we tested pre- and post-exercise headache, along with fatigue, heart rate (HR) responses, and prostaglandin E(2) (PGE(2)) salivary concentration. Although real O(2) breathing increased SO(2) along with a decrease in pre- and post-exercise headache, fatigue, HR, and PGE(2), placebo O(2) changed neither pre-/post-exercise headache nor SO(2)/HR/PGE(2), but it decreased fatigue. However, in another group of subjects, when sham O(2) was delivered after 2 previous exposures to O(2) (O(2) preconditioning), it decreased fatigue, post-exercise headache, HR, and PGE(2), yet without any increase in SO(2). Three main findings emerge from these data. First, placebo O(2) is effective in reducing post-exercise headache, along with HR and PGE(2) decrease, only after O(2) preconditioning. Second, pre-exercise (at rest) headache is not affected by placebo O(2), which emphasizes the limits of a placebo treatment at high altitude. Third, fatigue is affected by placebo O(2) even without prior O(2) conditioning, which suggests the higher placebo sensitivity of fatigue compared with headache pain at high altitude.

  5. Genetic diversities of MT-ND1 and MT-ND2 genes are associated with high-altitude adaptation in yak.

    PubMed

    Shi, Yu; Hu, Yongsong; Wang, Jie; Elzo, Mauricio A; Yang, Xue; Lai, Songjia

    2018-04-01

    Tibetan yak (Bos grunniens) inhabiting the Qinghai-Tibet Plateau (QTP) where the average altitude is 4000 m, is specially adapted to live at these altitudes. Conversely, cattle (B. taurus) has been found to suffer from high-altitude hypertension or heart failure when exposed to these high altitudes. Two mitochondrial genes, MT-ND1 and MT-ND2, encode two subunits of NADH dehydrogenase play an essential role in the electron transport chain of oxidative phosphorylation (OXPHOS). We sequenced these two mitochondrial genes in two bovine groups (70 Tibetan yaks and 70 Xuanhan cattle) and downloaded 300 sequences of B. taurus (cattle), 93 sequences of B. grunniens (domestic yak), and 2 sequences of B. mutus (wild yak) from NCBI to increase our understanding of the mechanisms of adaptability to hypoxia at high altitudes in yaks compared to cattle. MT-ND1 SNP m.3907 C > T, present in all Tibetan yaks, was positively associated with high-altitude adaptation (p < .0006). Specially, mutation m.3638 A > G present in all cattle, resulting in the termination of transcription, was negatively associated with high-altitude adaptation (p < .0006). Additionally, MT-ND2 SNPs m.4351 G > A and m.5218 C > T also showed positive associations with high-altitude adaptation (p < .0004). MT-ND1 haplotypes H2, H3, H4, H6, and H7 showed positive associations but haplotype H20 had a negative association with high-altitude adaptation (p < .0008). Similarly, MT-ND2 haplotypes Ha1 Ha8, Ha10, and Ha11 were positively associated whereas haplotype Ha2 was negatively associated with adaptability to high-altitudes (p < .0008). Thus, MT-ND1 and MT-ND2 can be considered as candidate genes associated with adaptation to high-altitude environments.

  6. Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

    PubMed Central

    Sun, Zhong-Lei; Jiang, Xian-Feng; Cheng, Yuan-Chi; Liu, Ying-Fu; Yang, Kai; Zhu, Shuang-Long; Kong, Xian-Bin; Tu, Yue; Bian, Ke-Feng; Liu, Zhen-Lin; Chen, Xu-Yi

    2018-01-01

    The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 μg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE. PMID:29722317

  7. The individual response to training and competition at altitude.

    PubMed

    Chapman, Robert F

    2013-12-01

    Performance in athletic activities that include a significant aerobic component at mild or moderate altitudes shows a large individual variation. Physiologically, a large portion of the negative effect of altitude on exercise performance can be traced to limitations of oxygen diffusion, either at the level of the alveoli or the muscle microvasculature. In the lung, the ability to maintain arterial oxyhaemoglobin saturation (SaO₂) appears to be a primary factor, ultimately influencing oxygen delivery to the periphery. SaO₂ in hypoxia can be defended by increasing ventilatory drive; however, during heavy exercise, many athletes demonstrate limitations to expiratory flow and are unable to increase ventilation in hypoxia. Additionally, increasing ventilatory work in hypoxia may actually be negative for performance, if dyspnoea increases or muscle blood flow is reduced secondary to an increased sympathetic outflow (eg, the muscle metaboreflex response). Taken together, some athletes are clearly more negatively affected during exercise in hypoxia than other athletes. With careful screening, it may be possible to develop a protocol for determining which athletes may be the most negatively affected during competition and/or training at altitude.

  8. Effects of high altitude and water deprivation on arginine vasopressin release in men.

    PubMed

    Maresh, C M; Kraemer, W J; Judelson, D A; VanHeest, J L; Trad, L; Kulikowich, J M; Goetz, K L; Cymerman, A; Hamilton, A J

    2004-01-01

    High-altitude exposure changes the distribution of body water and electrolytes. Arginine vasopressin (AVP) may influence these alterations. The purpose of this study was to examine the effect of a 24-h water deprivation trial (WDT) on AVP release after differing altitude exposures. Seven healthy males (age 22 +/- 1 yr, height 176 +/- 2 cm, mass 75.3 +/- 1.8 kg) completed three WDTs: at sea level (SL), after acute altitude exposure (2 days) to 4,300 m (AA), and after prolonged altitude exposure (20 days) to 4,300 m (PA). Body mass, standing and supine blood pressures, plasma osmolality (Posm), and plasma AVP (PAVP) were measured at 0, 12, 16, and 24 h of each WDT. Urine volume was measured at each void throughout testing. Baseline Posm increased from SL to altitude (SL 291.7 +/- 0.8 mosmol/kgH2O, AA 299.6 +/- 2.2 mosmol/kgH2O, PA 302.3 +/- 1.5 mosmol/kgH2O, P < 0.05); however, baseline PAVP measurements were similar. Despite similar Posm values, the maximal PAVP response during the WDT (at 16 h) was greater at altitude than at SL (SL 1.7 +/- 0.5 pg/ml, AA 6.4 +/- 0.7 pg/ml, PA 8.7 +/- 0.9 pg/ml, P < 0.05). In conclusion, hypoxia appeared to alter AVP regulation by raising the osmotic threshold and increasing AVP responsiveness above that threshold.

  9. The influence of chronic hypoxia upon chemoreception

    PubMed Central

    Powell, Frank L.

    2007-01-01

    Carotid body chemoreceptors are essential for time-dependent changes in ventilatory control during chronic hypoxia. Early theories of ventilatory acclimatization to hypoxia focused on time-dependent changes in known ventilatory stimuli, such as small changes in arterial pH that may play a significant role in some species. However, plasticity in the cellular and molecular mechanisms of carotid body chemoreception play a major role in ventilatory acclimatization to hypoxia in all species studied. Chronic hypoxia causes changes in (a) ion channels (potassium, sodium, calcium) to increase glomus cell excitability, and (b) neurotransmitters (dopamine, acetylcholine, ATP) and neuromodulators (endothelin-1) to increase carotid body afferent activity for a given PO2 and optimize O2-sensitivity. O2-sensing heme-containing molecules in the carotid body have not been studied in chronic hypoxia. Plasticity in medullary respiratory centers processing carotid body afferent input also contributes to ventilatory acclimatization to hypoxia. It is not known if the same mechanisms occur in patients with chronic hypoxemia from lung disease or high altitude natives. PMID:17291837

  10. Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

    PubMed Central

    Bogdanova, Olena V.; Olson, Paul R.; Sung, Young-Hoon; D'Anci, Kristen E.; Renshaw, Perry F.

    2015-01-01

    Abstract Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52–60, 2015—Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males. PMID:25803141

  11. Effects of growth, diving history, and high altitude on blood oxygen capacity in harbor seals

    NASA Technical Reports Server (NTRS)

    Kodama, A. M.; Elsner, R.; Pace, N.

    1977-01-01

    Blood volume and body composition for diving and nondiving harbor seals were measured at six-week intervals during a 10-month period of captitivity. Whole body hematocrit, red cell volume per kg of lean body mass, and total circulating hemoglobin per kg lean body mass were significantly higher in the diving group, but relatively large blood volumes expressed in terms of body weight (11-12%) were found in both groups. A pair of harbor seals exposed to high altitude for about three months registered significant increases in red cell volume, blood hemoglobin levels, and blood volume expressed in terms of body weight; results of alveolar gas analyses indicate that hyperventilation also occurred. These typical mammalian responses to hypoxia suggest that the harbor seal's large blood volume and high hemoglobin content are an expression of phylogenetic control, and that in spite of its adaptability to apnea during its diving life, the animal cannot be considered preacclimatized to high altitude.

  12. Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Newby, Elizabeth A.; Myers, Dean A.

    2015-01-01

    In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus. PMID:26173460

  13. Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

    PubMed

    Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

    2018-02-17

    The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

  14. Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc

    PubMed Central

    Jeong, Choongwon; Ozga, Andrew T.; Witonsky, David B.; Malmström, Helena; Edlund, Hanna; Hofman, Courtney A.; Hagan, Richard W.; Jakobsson, Mattias; Lewis, Cecil M.; Aldenderfer, Mark S.; Di Rienzo, Anna

    2016-01-01

    The high-altitude transverse valleys [>3,000 m above sea level (masl)] of the Himalayan arc from Arunachal Pradesh to Ladahk were among the last habitable places permanently colonized by prehistoric humans due to the challenges of resource scarcity, cold stress, and hypoxia. The modern populations of these valleys, who share cultural and linguistic affinities with peoples found today on the Tibetan plateau, are commonly assumed to be the descendants of the earliest inhabitants of the Himalayan arc. However, this assumption has been challenged by archaeological and osteological evidence suggesting that these valleys may have been originally populated from areas other than the Tibetan plateau, including those at low elevation. To investigate the peopling and early population history of this dynamic high-altitude contact zone, we sequenced the genomes (0.04×–7.25×, mean 2.16×) and mitochondrial genomes (20.8×–1,311.0×, mean 482.1×) of eight individuals dating to three periods with distinct material culture in the Annapurna Conservation Area (ACA) of Nepal, spanning 3,150–1,250 y before present (yBP). We demonstrate that the region is characterized by long-term stability of the population genetic make-up despite marked changes in material culture. The ancient genomes, uniparental haplotypes, and high-altitude adaptive alleles suggest a high-altitude East Asian origin for prehistoric Himalayan populations. PMID:27325755

  15. [Relationship of high altitude de-adaptation with acute high altitude response and cardiac function].

    PubMed

    Yang, Sheng-Yue; Zhou, Qi-Quan; Feng, En-Zhi; Yan, Zi-Qiang; Tian, Zhong-Xin; Yin, He; Shi, Zi-Fu

    2013-09-01

    To assess the relationship of high altitude de-adaptation response (HADAR) with acute high altitude response (AHAR) and cardiac function. Ninety-six military personnel of rapid entering into high altitude (3 700 to 4 800 m) with strong physical work were analyzed, all subjects were male, aged 18 - 35 years. According to the symptomatic scores of AHAR were divided into 3 groups: sever AHAR (group A, 24), mild to moderate AHAR (group B, 47) and non-AHAR (group C, 25) at high altitude. According to the symptomatic scores of HADAR were divided into 3 groups: severe HADAR (group E, 19), mild to moderate HADAR (group F, 40) and non-HADAR (group G, 37) after return to lower altitude (1 500 m). Mean pulmonary arterial pressure (mPAP), right ventricular internal dimension (RVID), outflow tract of right ventricle (RVOT), left ventricular internal dimension (LVID), left ventricular ejection fraction (LVEF), cardiac muscle work index (Tei index), creatine kinase isoenzymes-MB (CK-MB), lactic dehydrogenase isoenzyme-1 (LDH-1) were measured at high altitude stayed 50 days and after return to lower altitude 12 h, 15 d, and 30 d. Fifty healthy volunteers (group D) at 1 500 m altitude served as control. Level of mPAP, RVID, RVOT, RVID/LVID ratio, Tei index, CK-MB,and LDH-1 were higher, and LVEF was lower in group A than those in group B, C and D, there were significant differences between group B and C, C and D (all P < 0.01). AHAR scores were positively correlated with HADAR scores (r = 0.863, P < 0.01). Twelve hours after return to lower altitude, level of mPAP, RVID, RVOT, RVI/LVID ratio, Tei index, CK-MB, and LDH-1 were higher, and LVEF was lower in group E than those in group F, G and D, there were significant differences between group F and G, G and D (all P < 0.01). Fifteen days after return to lower altitude, level of mPAP, RVID, RVOT, RVID/LVID ratio were higher in group E than those in group F, G, and D, there were significant differences between group F and G, and D (P

  16. Ear - blocked at high altitudes

    MedlinePlus

    ... ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... to the eardrum) and the back of the nose and upper throat. ... down from high altitudes. Chewing gum the entire time you are ...

  17. The Effect of Acute and Chronic Exposure to Hypobaric Hypoxia on Loaded Squat Jump Performance

    PubMed Central

    García-Ramos, Amador; Padial, Paulino; De la Fuente, Blanca; Argüelles-Cienfuegos, Javier; Bonitch-Góngora, Juan

    2017-01-01

    Abstract The present study aimed (1) to compare loaded squat jump performance after an acute and chronic exposure to a moderate natural altitude between normoxia and hypobaric hypoxia conditions, and (2) to analyze the effect of an altitude training camp on loaded jump squat development. Sixteen male swimmers (17.1 ± 0.8 years) took part in a 17-day training camp at a natural moderate altitude. They were randomly tested in counterbalanced order on days 1 and 3 in normoxia and hypoxia (pretest) and on days 15 and 17 again in normoxia and hypoxia (posttest). The peak velocity reached with loads equivalent to 25%, 50%, 75% and 100% of swimmers’ pretest body weight in the loaded squat jump exercise was the dependent variable analyzed. An overall increase in peak velocity during the test performed in hypoxia of 6.5% in pretest (p < 0.001, ES = 0.98) and 4.5% in posttest (p < 0.001, ES = 0.81) was observed. An overall increment in peak velocity of 4.0% considering the data for normoxia tests (p < 0.001, ES = 0.61) and 2.1% considering the data for hypoxia tests (p = 0.008, ES = 0.36) was achieved after the altitude training camp. These results highlight the beneficial effects of hypobaric hypoxia on jump performance after short and longer term exposure to a natural moderate altitude. The increase in loaded squat jump performance following the 17-day training camp suggests that altitude training could constitute a favorable stimulus in explosive strength. PMID:28469753

  18. The role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn llamas.

    PubMed

    Reyes, Roberto V; Díaz, Marcela; Ebensperger, Germán; Herrera, Emilio A; Quezada, Sebastián A; Hernandez, Ismael; Sanhueza, Emilia M; Parer, Julian T; Giussani, Dino A; Llanos, Aníbal J

    2018-01-25

    Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. We show that high- compared to lowland newborn llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca 2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn llama. Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. The cardiopulmonary function of newborn llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn llamas showed lower in vivo pulmonary arterial

  19. Hypoxia-induced changes in standing balance.

    PubMed

    Wagner, Linsey S; Oakley, Sarah R; Vang, Pao; Noble, Brie N; Cevette, Michael J; Stepanek, Jan P

    2011-05-01

    A few studies in the literature have reported postural changes with hypoxia, but none have quantified the magnitude of change. Further understanding of this condition could have implications for patients at risk for falls, individuals undergoing acute altitude exposure, and pilots and commercial passengers. The objective of this study was to evaluate the effect of different levels of hypoxia (oxygen nitrogen mixtures) on postural standing balance using the computerized dynamic posturography (CDP) system. This improves upon previous protocols by manipulating vision and standing balance with a sway-referenced visual field and/or platform. Additionally, normative data were available for comparison with the cumulative test scores and scores for each condition. Altitude hypoxia was simulated by use of admixing nitrogen to the breathing gas to achieve equivalent altitudes of 1524 m, 2438 m, and 3048 m. Subjects were evaluated using the CDP system. Subjects showed an overall trend toward decreased performance at higher simulated altitudes consistent with the initial hypothesis. Composite standing balance sway scores for the sensory organization subtest of CDP were decreased compared to baseline for simulated altitudes as low as 2438 m (mean sway scores: 81.92 at baseline; 81.85 at 1524 m; 79.15 at 2438 m; 79.15 at 3048 m). Reaction times to unexpected movements in the support surface for the motor control subtest (MCT) increased compared to baseline (mean composite scores: 133.3 at baseline; 135.9 ms at 1524 m; 138.0 ms at 2438 m; 140.9 ms at 3048 m). The CDP testing provided a reliable objective measurement of degradation of balance under hypoxic conditions.

  20. Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

    PubMed

    Rimoldi, Stefano F; Rexhaj, Emrush; Duplain, Hervé; Urben, Sébastien; Billieux, Joël; Allemann, Yves; Romero, Catherine; Ayaviri, Alejandro; Salinas, Carlos; Villena, Mercedes; Scherrer, Urs; Sartori, Claudio

    2016-02-01

    To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Preventing High Altitude Cerebral Edema in Rats with Repurposed Anti-Angiogenesis Pharmacotherapy.

    PubMed

    Tarshis, Samantha; Maltzahn, Joanne; Loomis, Zoe; Irwin, David C

    2016-12-01

    High altitude cerebral edema (HACE) is a fulminant, deadly, and yet still unpredictable brain disease. A new prophylactic treatment for HACE and its predecessor, acute mountain sickness (AMS), needs to be developed without the contraindications or adverse effect profiles of acetazolamide and dexamethasone. Since neovascularization signals are likely key contributors to HACE/AMS, our approach was to examine already existing anti-angiogenic drugs to inhibit potential initiating HACE pathway(s). This approach can also reveal crucial early steps in the frequently debated mechanism of HACE/AMS pathogenesis. We exposed four rat cohorts to hypobaric hypoxia and one to sea level (hyperbaric) conditions. The cohorts were treated with saline controls, an anti-angiogenesis drug (motesanib), a pro-angiogenesis drug (deferoxamine), or an intraperitoneal version of the established AMS prophylaxis drug, acetazolamide (benzolamide). Brain tissue was analyzed for cerebrovascular leak using the Evans Blue Dye (EVBD) protocol. We observed significantly increased EVBD in the altitude control and pro-angiogenesis (deferoxamine) cohorts, and significantly decreased EVBD in the anti-angiogenesis (motesanib), established treatment (benzolamide), and sea-level cohorts. Anti-angiogenesis-treated cohorts demonstrated less cerebrovascular extravasation than the altitude control and pro-angiogenesis treated rats, suggesting promise as an alternative prophylactic HACE/AMS treatment. The leak exacerbation with pro-angiogenesis treatment and improvement with anti-angiogenesis treatment support the hypothesis of early neovascularization signals provoking HACE. We demonstrate statistically significant evidence to guide further investigation for VEGF- and HIF-inhibitors as HACE/AMS prophylaxis, and as elucidators of still unknown HACE pathogenesis.Tarshis S, Maltzahn J, Loomis Z, Irwin DC. Preventing high altitude cerebral edema in rats with repurposed anti-angiogenesis pharmacotherapy. Aerosp Med

  2. Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders.

    PubMed

    Salvi, Paolo; Faini, Andrea; Castiglioni, Paolo; Brunacci, Fausto; Montaguti, Luca; Severi, Francesca; Gautier, Sylvie; Pretolani, Enzo; Benetos, Athanase; Parati, Gianfranco

    2018-06-21

    The physiological relevance of slow-wave vasomotion is still unclear, even it has been hypothesized it could be a compensatory mechanism enhancing tissue oxygenation in conditions of reduced oxygen supply. Aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during post-occlusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 males; aged 29-39yrs) at 1350, 3400 and 5050m, and from 10 Nepalese male highlanders (aged 21-39yrs) at 3400 and 5050m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61yrs) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15Hz vasomotion amplitude [power spectral density % expressed as geometric means (geometric standard deviation) =14.0(3.6) at 1350m; 87.0(2.3) at 3400m and 249.8(3.6) at 5050m, p=0.006 and p<0.001 vs 1350m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % =183.4(4.1) at 3400m vs 236.0(3.0) at 5050m, p=0.139]. In both groups at altitude it was further increased after ischemic stimulus (p<0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction.

  3. Pulmonary vascular responsiveness in rats following neonatal exposure to high altitude or carbon monoxide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tucker, A.; Penney, D.G.

    1993-01-01

    Exposure of adult and neonatal rats to high altitude increases pulmonary vascular responsiveness during the exposure. A study was undertaken to determine if a short exposure of neonatal rats to either high-altitude or carbon monoxide (CO) hypoxia would cause persistent alterations in pulmonary vascular responsiveness postexposure. One-day-old male Sprague-Dawley rats were obtained as 16 litters of 10-12 pups each. At 2 days of age, 4 litters were exposed to CO (500 ppm) for 32 days, and 4 litters were exposed to ambient air (AIR) in Detroit (200 m). Another 4 litters were exposed to 3500 m altitude (ALT) in amore » chamber for 32 days, and 3 litters were exposed to ambient conditions in Fort Collins (CON, 1524 m). After the exposures, all rats were maintained at 1524 m. At 2, 40, 76 and 112 days postexposure, lungs were isolated and perfused with Earle's salt solution (+Ficoll, 4 g%). Pulmonary vascular responsiveness was assessed by dose responses to angiotensin II (AII, 0.025-0.40 [mu]g) and acute hypoxia (3% O[sub 2] for 3 min). AII responses were higher in ALT vs CON rats at 2 and 40 days postexposure, but no differences were noted between CO and AIR rats. Baseline pulmonary vascular resistance and pulmonary arterial pressure (in isolated lungs) were higher in ALT rats at all four ages compared to the other three groups. Both the ALT and CO rats displayed hypertrophy of the right ventricle (RV) and the left ventricle (LV) at the termination of treatment and elevated hematocrit. LV hypertrophy and polycythemia regressed with time, but RV hypertrophy remained significant in the ALT rats through 112 days postexposure. The results indicate that neonatal exposure to ALT, but no CO, causes a persistent increase in pulmonary vascular responsiveness and RV hypertrophy for at least 112 days after termination of the exposure. 40 refs., 3 figs., 2 tabs.« less

  4. Regulation of erythropoiesis by hypoxia-inducible factors

    PubMed Central

    Haase, Volker H.

    2012-01-01

    A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate this response by inducing cell-type specific gene expression changes that result in increased erythropoietin (EPO) production in kidney and liver, in enhanced iron uptake and utilization and in adjustments of the bone marrow microenvironment that facilitate erythroid progenitor maturation and proliferation. In particular HIF-2 has emerged as the transcription factor that regulates EPO synthesis in the kidney and liver and plays a critical role in the regulation of intestinal iron uptake. Its key function in the hypoxic regulation of erythropoiesis is underscored by genetic studies in human populations that live at high-altitude and by mutational analysis of patients with familial erythrocytosis. This review provides a perspective on recent insights into HIF-controlled erythropoiesis and iron metabolism, and examines cell types that have EPO-producing capability. Furthermore, the review summarizes clinical syndromes associated with mutations in the O2-sensing pathway and the genetic changes that occur in high altitude natives. The therapeutic potential of pharmacologic HIF activation for the treatment of anemia is discussed. PMID:23291219

  5. Heart rate variabilty changes during first week of acclimatization to 3500 m altitude in Indian military personnel.

    PubMed

    Bhaumik, G; Dass, D; Bhattacharyya, D; Sharma, Y K; Singh, S B

    2013-01-01

    Acute exposure to hypobaric hypoxia induces the changes in autonomic control of heart rate. Due to emergencies or war like conditions, rapid deployment of Indian military personnel into high altitude frequently occurs. Rapid deployment to high altitude soldiers are at risk of developing high altitude sickness. The present study was conducted to evaluate the acute exposure to high altitude hypobaric hypoxia (3500 m altitude) on the autonomic nervous control of heart rate in Indian military personnel during first week of acclimatization Indices of heart rate variability (viz; R-R interval, total power, low frequency, high frequency, ratio of low to high frequency) and pulse arterial oxygen saturation were measured at sea level and 3500m altitude. Power spectrum of heart rate variability was quantified by low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.5 Hz) widths. The ratio of LF to HF was also assessed as an index of the sympathovagal balance. Mean R-R interval decreased significantly on day 2 on induction to altitude which tended to increase on day 5. Total power (TP) decreased high altitude and tended to recover within a week. Both HF and LF power showed decrement at 3500m in comparison to sea level. The ratio of LF to HF (LF/HF) at 3500m was significantly higher at 3500m. SpO2 values decreased significantly (P < 0.05) at high altitude on day-2 which increased on day-5. We conclude that autonomic control of the heart rate measured by heart rate variability was altered on acute induction to 3500m which showed a significant decrease in parasympathetic tone and increase in sympathetic tone, then acclimatization seems to be characterized by progressive shift toward a higher parasympathetic tone.

  6. Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in the rat.

    PubMed

    Prasad, Jyotsna; Baitharu, Iswar; Sharma, Alpesh Kumar; Dutta, Ruma; Prasad, Dipti; Singh, Shashi Bala

    2013-12-01

    Inadequate oxygen availability at high altitude causes elevated oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. Though oxidative stress is known to be a major cause of neurodegeneration in hypobaric hypoxia, neuroprotective and ameliorative potential of quercetin, a flavonoid with strong antioxidant properties in reversing hypobaric hypoxia-induced memory impairment has not been studied. Four groups of male adult Sprague Dawley rats were exposed to hypobaric hypoxia for 7 days in an animal decompression chamber at an altitude of 7600 meters. Rats were supplemented with quercetin orally by gavage during 7 days of hypoxic exposure. Spatial working memory was assessed by a Morris Water Maze before and after exposure to hypobaric hypoxia. Changes in oxidative stress markers and apoptotic marker caspase 3 expression in hippocampus were assessed. Histological assessment of neurodegeneration was performed by cresyl violet and fluoro Jade B staining. Our results showed that quercetin supplementation during exposure to hypobaric hypoxia decreased reactive oxygen species levels and consequent lipid peroxidation in the hippocampus by elevating antioxidant status and free radical scavenging enzyme system. There was reduction in caspase 3 expression, and decrease in the number of pyknotic and fluoro Jade B-positive neurons in hippocampus after quercetin supplementation during hypoxic exposure. Behavioral studies showed that quercetin reversed the hypobaric hypoxia-induced memory impairment. These findings suggest that quercetin provides neuroprotection to hippocampal neurons during exposure to hypobaric hypoxia through antioxidative and anti-apoptotic mechanisms, and possesses promising therapeutic potential to ameliorate hypoxia-induced memory dysfunction.

  7. COPD and air travel: does hypoxia-altitude simulation testing predict in-flight respiratory symptoms?

    PubMed

    Edvardsen, Anne; Ryg, Morten; Akerø, Aina; Christensen, Carl Christian; Skjønsberg, Ole H

    2013-11-01

    The reduced pressure in an aircraft cabin may cause significant hypoxaemia and respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). The current study evaluated whether there is a relationship between hypoxaemia obtained during hypoxia-altitude simulation testing (HAST), simulating an altitude of 2438 m, and the reporting of respiratory symptoms during air travel. 82 patients with moderate to very severe COPD answered an air travel questionnaire. Arterial oxygen tensions during HAST (PaO2HAST) in subjects with and without in-flight respiratory symptoms were compared. The same questionnaire was answered within 1 year after the HAST. Mean ± sd PaO2HAST was 6.3 ± 0.6 kPa and 62 (76%) of the patients had PaO2HAST <6.6 kPa. 38 (46%) patients had experienced respiratory symptoms during air travel. There was no difference in PaO2HAST in those with and those without in-flight respiratory symptoms (6.3 ± 0.7 kPa versus 6.3 ± 0.6 kPa, respectively; p=0.926). 54 (66%) patients travelled by air after the HAST, and patients equipped with supplemental oxygen (n = 23, 43%) reported less respiratory symptoms when flying with than those without such treatment (four (17%) versus 11 (48%) patients; p=0.039). In conclusion, no difference in PaO2HAST was found between COPD patients with and without respiratory symptoms during air travel.

  8. Increased Lung Volume in Infants and Toddlers at High Compared to Low Altitude

    PubMed Central

    Llapur, Conrado J.; Martínez, Myriam R.; Caram, María Marta; Bonilla, Federico; Cabana, Celia; Yu, Zhansheng; Tepper, Robert S.

    2015-01-01

    Summary Children and adults residing at high altitude (HA) compared to low altitude (LA) have larger lung volumes; however, it is unknown whether this response to chronic hypoxia begins early in life. Our objective was to determine whether infants and toddlers at HA have larger lung volumes compared to infants and toddlers at LA. Oxygen saturation (SaO2), functional residual capacity (FRC), as well as serum levels of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) were measured in infants and toddlers from HA (N = 50; 3,440 m) and LA (N = 35; 440 m). There were no significant differences in somatic size for HA and LA subjects; however, HA subjects had significantly lower SaO2 (88.5% vs. 96.7%; P < 0.0001). Subjects at HA had significantly greater FRC compared to subjects at LA (group mean: 209 and 157 ml; P < 0.0001), adjusting for body length. Male infants at HA had a significantly greater FRC compared to males at LA (57 ml; P-value < 0.001); however, the increase in FRC for females at HA compared to LA was not significant (20 ml; P-value = 0.101). VEGF and EPO were significantly higher for subjects at HA compared to LA with no gender differences. In summary, infants and toddlers at HA have lower oxygen saturations, higher serum levels of VEGF and EPO, and higher FRC compared to subjects at LA; however, chronic hypoxia appears to generate a more robust response in lung growth in male compared to female infants early in life. PMID:23401418

  9. Effects of acute hypoxia on heart rate variability, sample entropy and cardiorespiratory phase synchronization.

    PubMed

    Zhang, Da; She, Jin; Zhang, Zhengbo; Yu, Mengsun

    2014-06-11

    Investigating the responses of autonomic nervous system (ANS) in hypoxia may provide some knowledge about the mechanism of neural control and rhythmic adjustment. The integrated cardiac and respiratory system display complicated dynamics that are affected by intrinsic feedback mechanisms controlling their interaction. To probe how the cardiac and respiratory system adjust their rhythms in different simulated altitudes, we studied heart rate variability (HRV) in frequency domain, the complexity of heartbeat series and cardiorespiratory phase synchronization (CRPS) between heartbeat intervals and respiratory cycles. In this study, twelve male subjects were exposed to simulated altitude of sea level, 3000 m and 4000 m in a hypobaric chamber. HRV was assessed by power spectral analysis. The complexity of heartbeat series was quantified by sample entropy (SampEn). CRPS was determined by cardiorespiratory synchrogram. The power spectral HRV indices at all frequency bands depressed according to the increase of altitude. The SampEn of heartbeat series increased significantly with the altitude (P < 0.01). The duration of CRPS epochs at 3000 m was not significantly different from that at sea level. However, it was significantly longer at 4000 m (P < 0.01). Our results suggest the phenomenon of CRPS exists in normal subjects when they expose to acute hypoxia. Further, the autonomic regulation has a significantly stronger influence on CRPS in acute hypoxia. The changes of CRPS and HRV parameters revealed the different regulatory mechanisms of the cardiac and respiratory system at high altitude.

  10. The effects of hypobaric hypoxia (50.6 kPa) on blood components in guinea-pigs.

    PubMed

    Osada, H

    1991-06-01

    One hundred and five male (Hartley) guinea-pigs weighing 350-380 g and 30 splenectomized guinea-pigs were exposed to simulated hypobaric hypoxia of 50.6 kPa (equal to an altitude of 5486 m) for 14 days. The partial pressure of oxygen was set at half that at sea level. The white blood cell count increased significantly on day 3 of the simulated high altitude experiment but returned to normal on day 7, whereas the red blood cell count increased continuously. To study the effect of high altitude exposure on platelets, the platelet count in the splenectomized group was compared to that in a non-splenectomized group. Investigation of the resistance of red blood cell membranes to osmotic pressure under hypobaric conditions revealed a shift of the onset of haemolysis in the hyperosmotic direction. These findings may help to increase our understanding of the biochemical mechanisms of adaptation to hypobaric hypoxia.

  11. Physiological responses and evaluation of effects of BMI, smoking and drinking in high altitude acclimatization: a cohort study in Chinese Han young males.

    PubMed

    Peng, Qian-Qian; Basang, Zhuoma; Cui, Chao-Ying; Li, Lei; Qian, Ji; Gesang, Quzhen; Yang, La; La, Zong; De, Yang; Dawa, Puchi; Qu, Ni; Suo, Qu; Dan, Zhen; Xiao, Duoji; Wang, Xiao-Feng; Jin, Li

    2013-01-01

    High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied.

  12. Physiological Responses and Evaluation of Effects of BMI, Smoking and Drinking in High Altitude Acclimatization: A Cohort Study in Chinese Han Young Males

    PubMed Central

    Cui, Chao-ying; Li, Lei; Qian, Ji; Gesang, Quzhen; Yang, La; La, Zong; De, Yang; Dawa, Puchi; Qu, Ni; Suo, Qu; Dan, Zhen; Xiao, Duoji; Wang, Xiao-feng; Jin, Li

    2013-01-01

    High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied. PMID:24260204

  13. Genomic Analyses Reveal Potential Independent Adaptation to High Altitude in Tibetan Chickens.

    PubMed

    Wang, Ming-Shan; Li, Yan; Peng, Min-Sheng; Zhong, Li; Wang, Zong-Ji; Li, Qi-Ye; Tu, Xiao-Long; Dong, Yang; Zhu, Chun-Ling; Wang, Lu; Yang, Min-Min; Wu, Shi-Fang; Miao, Yong-Wang; Liu, Jian-Ping; Irwin, David M; Wang, Wen; Wu, Dong-Dong; Zhang, Ya-Ping

    2015-07-01

    Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Zupet, P.; Finderle, Z.; Schlegel, Todd T.; Starc, V.

    2010-01-01

    Ventricular repolarization instability as quantified by the index of QT interval variability (QTVI) is one of the best predictors for risk of malignant ventricular arrhythmias and sudden cardiac death. Because it is difficult to appropriately monitor early signs of organ dysfunction at high altitude, we investigated whether high resolution advanced ECG (HR-ECG) analysis might be helpful as a non-invasive and easy-to-use tool for evaluating the risk of cardiac arrhythmias during exposure to acute hypoxia. 19 non-acclimatized healthy trained alpinists (age 37, 8 plus or minus 4,7 years) participated in the study. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position breathing room air and then after breathing 12.5% oxygen for 30 min. For beat-to-beat RR and QT variability, the program of Starc was utilized to derive standard time domain measures such as root mean square of the successive interval difference (rMSSD) of RRV and QTV, the corrected QT interval (QTc) and the QTVI in lead II. Changes were evaluated with paired-samples t-test with p-values less than 0.05 considered statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with p = 0.000 and p = 0.005, respectively. Significant increases were found in both the rMSSDQT and the QTVI in lead II, with p = 0.002 and p = 0.003, respectively. There was no change in QTc interval length (p = non significant). QT variability parameters may be useful for evaluating changes in ventricular repolarization caused by hypoxia. These changes might be driven by increases in sympathetic nervous system activity at ventricular level.

  15. Cardiac responses to hypoxia and reoxygenation in Drosophila.

    PubMed

    Zarndt, Rachel; Piloto, Sarah; Powell, Frank L; Haddad, Gabriel G; Bodmer, Rolf; Ocorr, Karen

    2015-12-01

    An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-α), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation. Copyright © 2015 the American Physiological Society.

  16. The effect of intermittent hypobaric-hypoxia treatments on renal glutathione peroxidase activity of rats

    NASA Astrophysics Data System (ADS)

    Paramita, I. A.; Jusman, S. W. A.

    2017-08-01

    Many people living at high altitudes experiencing a condition called intermittent hypobaric hypoxia (IHH). Some people even create IHH condition as an exercise for pilots, athletes, and mountaineers. In this experiment, we aimed to determine whether the protective effect of IHH is mediated through glutathione peroxidase (GPX) enzyme. The experiment’s sample is two-month-old healthy Sprague-Dawley rat kidneys weighing 200-250 g. Intermittent hypobaric hypoxia treatment is done using a Hypobaric Chamber type I that can mimic air pressure at certain altitudes: 35,000 (one minute), 30,000 (three minutes), 25,000 (five minutes), and 18,000 (30 minutes) feet. The rats were divided into five treatment groups, including a control group, hypobaric-hypoxia group, and intermittent hypobaric-hypoxia 1x, 2x, and 3x groups with each group consisting of three rats. The specific activity of GPX was measured using RANDOX and RANSEL methods. The statistical analysis of one way-ANOVA did not show significant differences between the groups (p > 0.05), although specific activities of the renal GPX of rats exposed to hypobaric-hypoxia were higher than the control group. This may be caused by the other antioxidants’ activities. In conclusion, the IHH treatment did not affect GPX activity in the rat kidneys.

  17. Short-term adaptation and chronic cardiac remodelling to high altitude in lowlander natives and Himalayan Sherpa.

    PubMed

    Stembridge, Mike; Ainslie, Philip N; Shave, Rob

    2015-11-01

    What is the topic of this review? At high altitude, the cardiovascular system must adapt in order to meet the metabolic demand for oxygen. This review summarizes recent findings relating to short-term and life-long cardiac adaptation to high altitude in the context of exercise capacity. What advances does it highlight? Both Sherpa and lowlanders exhibit smaller left ventricular volumes at high altitude; however, myocardial relaxation, as evidenced by diastolic untwist, is reduced only in Sherpa, indicating that short-term hypoxia does not impair diastolic relaxation. Potential remodelling of systolic function, as evidenced by lower left ventricular systolic twist in Sherpa, may facilitate the requisite sea-level mechanical reserve required during exercise, although this remains to be confirmed. Both short-term and life-long high-altitude exposure challenge the cardiovascular system to meet the metabolic demand for O2 in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However, our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimize myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in high-altitude Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest and discuss the potential consequences

  18. Increased lung volume in infants and toddlers at high compared to low altitude.

    PubMed

    Llapur, Conrado J; Martínez, Myriam R; Caram, María Marta; Bonilla, Federico; Cabana, Celia; Yu, Zhansheng; Tepper, Robert S

    2013-12-01

    Children and adults residing at high altitude (HA) compared to low altitude (LA) have larger lung volumes; however, it is unknown whether this response to chronic hypoxia begins early in life. Our objective was to determine whether infants and toddlers at HA have larger lung volumes compared to infants and toddlers at LA. Oxygen saturation (SaO2 ), functional residual capacity (FRC), as well as serum levels of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) were measured in infants and toddlers from HA (N = 50; 3,440 m) and LA (N = 35; 440 m). There were no significant differences in somatic size for HA and LA subjects; however, HA subjects had significantly lower SaO2 (88.5% vs. 96.7%; P < 0.0001). Subjects at HA had significantly greater FRC compared to subjects at LA (group mean: 209 and 157 ml; P < 0.0001), adjusting for body length. Male infants at HA had a significantly greater FRC compared to males at LA (57 ml; P-value < 0.001); however, the increase in FRC for females at HA compared to LA was not significant (20 ml; P-value = 0.101). VEGF and EPO were significantly higher for subjects at HA compared to LA with no gender differences. In summary, infants and toddlers at HA have lower oxygen saturations, higher serum levels of VEGF and EPO, and higher FRC compared to subjects at LA; however, chronic hypoxia appears to generate a more robust response in lung growth in male compared to female infants early in life. © 2013 Wiley Periodicals, Inc.

  19. Hypoxia and flight performance of military instructor pilots in a flight simulator.

    PubMed

    Temme, Leonard A; Still, David L; Acromite, Michael T

    2010-07-01

    Military aircrew and other operational personnel frequently perform their duties at altitudes posing a significant hypoxia risk, often with limited access to supplemental oxygen. Despite the significant risk hypoxia poses, there are few studies relating it to primary flight performance, which is the purpose of the present study. Objective, quantitative measures of aircraft control were collected from 14 experienced, active duty instructor pilot volunteers as they breathed an air/nitrogen mix that provided an oxygen partial pressure equivalent to the atmosphere at 18,000 ft (5486.4 m) above mean sea level. The flight task required holding a constant airspeed, altitude, and heading at an airspeed significantly slower than the aircraft's minimum drag speed. The simulated aircraft's inherent instability at the target speed challenged the pilot to maintain constant control of the aircraft in order to minimize deviations from the assigned flight parameters. Each pilot's flight performance was evaluated by measuring all deviations from assigned target values. Hypoxia degraded the pilot's precision of altitude and airspeed control by 53%, a statistically significant decrease in flight performance. The effect on heading control effects was not statistically significant. There was no evidence of performance differences when breathing room air pre- and post-hypoxia. Moderate levels of hypoxia degraded the ability of military instructor pilots to perform a precision slow flight task. This is one of a small number of studies to quantify an effect of hypoxia on primary flight performance.

  20. Enhanced muscular oxygen extraction in athletes exaggerates hypoxemia during exercise in hypoxia.

    PubMed

    Van Thienen, Ruud; Hespel, Peter

    2016-02-01

    High rate of muscular oxygen utilization facilitates the development of hypoxemia during exercise at altitude. Because endurance training stimulates oxygen extraction capacity, we investigated whether endurance athletes are at higher risk to developing hypoxemia and thereby acute mountain sickness symptoms during exercise at simulated high altitude. Elite athletes (ATL; n = 8) and fit controls (CON; n = 7) cycled for 20 min at 100 W (EX100W), as well as performed an incremental maximal oxygen consumption test (EXMAX) in normobaric hypoxia (0.107 inspired O2 fraction) or normoxia (0.209 inspired O2 fraction). Cardiorespiratory responses, arterial Po2 (PaO2), and oxygenation status in m. vastus lateralis [tissue oxygenation index (TOIM)] and frontal cortex (TOIC) by near-infrared spectroscopy, were measured. Muscle O2 uptake rate was estimated from change in oxyhemoglobin concentration during a 10-min arterial occlusion in m. gastrocnemius. Maximal oxygen consumption in normoxia was 70 ± 2 ml·min(-1·)kg(-1) in ATL vs. 43 ± 2 ml·min(-1·)kg(-1) in CON, and in hypoxia decreased more in ATL (-41%) than in CON (-25%, P < 0.05). Both in normoxia at PaO2 of ∼95 Torr, and in hypoxia at PaO2 of ∼35 Torr, muscle O2 uptake was twofold higher in ATL than in CON (0.12 vs. 0.06 ml·min(-1)·100 g(-1); P < 0.05). During EX100W in hypoxia, PaO2 dropped to lower (P < 0.05) values in ATL (27.6 ± 0.7 Torr) than in CON (33.5 ± 1.0 Torr). During EXMAX, but not during EX100W, TOIM was ∼15% lower in ATL than in CON (P < 0.05). TOIC was similar between the groups at any time. This study shows that maintenance of high muscular oxygen extraction rate at very low circulating PaO2 stimulates the development of hypoxemia during submaximal exercise in hypoxia in endurance-trained individuals. This effect may predispose to premature development of acute mountain sickness symptoms during exercise at altitude. Copyright © 2016 the American Physiological Society.

  1. The re-establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude

    PubMed Central

    van Hall, G; Calbet, J A L; Søndergaard, H; Saltin, B

    2001-01-01

    One to five weeks of chronic exposure to hypoxia has been shown to reduce peak blood lactate concentration compared to acute exposure to hypoxia during exercise, the high altitude ‘lactate paradox’. However, we hypothesize that a sufficiently long exposure to hypoxia would result in a blood lactate and net lactate release from the active leg to an extent similar to that observed in acute hypoxia, independent of work intensity. Six Danish lowlanders (25–26 years) were studied during graded incremental bicycle exercise under four conditions: at sea level breathing either ambient air (0 m normoxia) or a low-oxygen gas mixture (10 % O2 in N2, 0 m acute hypoxia) and after 9 weeks of acclimatization to 5260 m breathing either ambient air (5260 m chronic hypoxia) or a normoxic gas mixture (47 % O2 in N2, 5260 m acute normoxia). In addition, one-leg knee-extensor exercise was performed during 5260 m chronic hypoxia and 5260 m acute normoxia. During incremental bicycle exercise, the arterial lactate concentrations were similar at sub-maximal work at 0 m acute hypoxia and 5260 m chronic hypoxia but higher compared to both 0 m normoxia and 5260 m acute normoxia. However, peak lactate concentration was similar under all conditions (10.0 ± 1.3, 10.7 ± 2.0, 10.9 ± 2.3 and 11.0 ± 1.0 mmol l−1) at 0 m normoxia, 0 m acute hypoxia, 5260 m chronic hypoxia and 5260 m acute normoxia, respectively. Despite a similar lactate concentration at sub-maximal and maximal workload, the net lactate release from the leg was lower during 0 m acute hypoxia (peak 8.4 ± 1.6 mmol min−1) than at 5260 m chronic hypoxia (peak 12.8 ± 2.2 mmol min−1). The same was observed for 0 m normoxia (peak 8.9 ± 2.0 mmol min−1) compared to 5260 m acute normoxia (peak 12.6 ± 3.6 mmol min−1). Exercise after acclimatization with a small muscle mass (one-leg knee-extensor) elicited similar lactate concentrations (peak 4.4 ± 0.2 vs. 3.9 ± 0.3 mmol l−1) and net lactate release (peak 16.4 ± 1

  2. High Altitude Launch for a Practical SSTO

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.; Denis, Vincent

    2003-01-01

    Existing engineering materials allow the construction of towers to heights of many kilometers. Orbital launch from a high altitude has significant advantages over sea-level launch due to the reduced atmospheric pressure, resulting in lower atmospheric drag on the vehicle and allowing higher rocket engine performance. High-altitude launch sites are particularly advantageous for single-stage to orbit (SSTO) vehicles, where the payload is typically 2 percent of the initial launch mass. An earlier paper enumerated some of the advantages of high altitude launch of SSTO vehicles. In this paper, we calculate launch trajectories for a candidate SSTO vehicle, and calculate the advantage of launch at launch altitudes 5 to 25 kilometer altitudes above sea level. The performance increase can be directly translated into increased payload capability to orbit, ranging from 5 to 20 percent increase in the mass to orbit. For a candidate vehicle with an initial payload fraction of 2 percent of gross lift-off weight, this corresponds to 31 percent increase in payload (for 5-kilometer launch altitude) to 122 percent additional payload (for 25-kilometer launch altitude).

  3. High Altitude Launch for a Practical SSTO

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.; Denis, Vincent

    2003-01-01

    Existing engineering materials allow the construction of towers to heights of many kilometers. Orbital launch from a high altitude has significant advantages over sea-level launch due to the reduced atmospheric pressure, resulting in lower atmospheric drag on the vehicle and allowing higher rocket engine performance. high-altitude launch sites are particularly advantageous for single-stage to orbit (SSTO) vehicles, where the payload is typically 2% of the initial launch mass. An earlier paper enumerated some of the advantages of high altitude launch of SSTO vehicles. In this paper, we calculate launch trajectories for a candidate SSTO vehicle, and calculate the advantage of launch at launch altitudes 5 to 25 kilometer altitudes above sea level. The performance increase can be directly translated in to increased payload capability to orbit, ranging from 5 to 20% increase in the mass to orbit. For a candidate vehicle with an initial payload fraction of 2% of gross lift-off weight, this corresponds to 31 % increase in payload (for 5-km launch altitude) to 122% additional payload (for 25-km launch altitude).

  4. High Altitude Launch for a Practical SSTO

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A.; Denis, Vincent; Lyons, Valerie (Technical Monitor)

    2003-01-01

    Existing engineering materials allow the construction of towers to heights of many kilometers. Orbital launch from a high altitude has significant advantages over sea-level launch due to the reduced atmospheric pressure, resulting in lower atmospheric drag on the vehicle and allowing higher rocket engine performance. High-altitude launch sites are particularly advantageous for single-stage to orbit (SSTO) vehicles, where the payload is typically 2% of the initial launch mass. An earlier paper enumerated some of the advantages of high altitude launch of SSTO vehicles. In this paper, we calculate launch trajectories for a candidate SSTO vehicle, and calculate the advantage of launch at launch altitudes 5 to 25 kilometer altitudes above sea level. The performance increase can be directly translated into increased payload capability to orbit, ranging from 5 to 20% increase in the mass to orbit. For a candidate vehicle with an initial payload fraction of 2% of gross lift-off weight, this corresponds to 31% increase in payload (for 5-km launch altitude) to 122% additional payload (for 25-km launch altitude).

  5. High Altitude Launch for a Practical SSTO

    NASA Astrophysics Data System (ADS)

    Landis, Geoffrey A.; Denis, Vincent

    2003-01-01

    Existing engineering materials allow the constuction of towers to heights of many kilometers. Orbital launch from a high altitude has significant advantages over sea-level launch due to the reduced atmospheric pressure, resulting in lower atmospheric drag on the vehicle and allowing higher rocket engine performance. High-altitude launch sites are particularly advantageous for single-stage to orbit (SSTO) vehicles, where the payload is typically 2% of the initial launch mass. An earlier paper enumerated some of the advantages of high altitude launch of SSTO vehicles. In this paper, we calculate launch trajectories for a candidate SSTO vehicle, and calculate the advantage of launch at launch altitudes 5 to 25 kilometer altitudes above sea level. The performance increase can be directly translated into increased payload capability to orbit, ranging from 5 to 20% increase in the mass to orbit. For a candidate vehicle with an initial payload fraction of 2% of gross lift-off weight, this corresponds to 31% increase in payload (for 5-km launch altitude) to 122% additional payload (for 25-km launch altitude).

  6. Influence of hypobaric hypoxia on bispectral index and spectral entropy in volunteers.

    PubMed

    Ikeda, T; Yamada, S; Imada, T; Matsuda, H; Kazama, T

    2009-08-01

    Hypoxia has been shown to change electroencephalogram parameters including frequency and amplitude, and may thus change bispectral index (BIS) and spectral entropy values. If hypoxia per se changes BIS and spectral entropy values, BIS and spectral entropy values may not correctly reflect the depth of anaesthesia during hypoxia. The aim of this study was to examine the changes in BIS and spectral entropy values during hypobaric hypoxia in volunteers. The study was conducted in a high-altitude chamber with 11 volunteers. After the subjects breathed 100% oxygen for 15 min at the ground level, the simulated altitude increased gradually to the 7620 m (25,000 ft) level while the subjects continued to breathe oxygen. Then, the subjects discontinued to breath oxygen and breathed room air at the 7620 m level for up to 5 min until they requested to stop hypoxic exposure. Oxygen saturation (SpO2), heart rate, 95% spectral edge frequency (SEF), BIS, response entropy (RE), and state entropy (SE) of spectral entropy were recorded throughout the study period. Of the 11 subjects, seven subjects who underwent hypoxic exposure for 4 min were analysed. SpO2 decreased to 69% at the 7620 m level without oxygen. However, SEF, BIS, RE, and SE before and during hypoxic exposure were almost identical. These data suggest that hypoxia of oxygen saturation around 70% does not have a strong effect on BIS and spectral entropy.

  7. Lower Obesity Rate during Residence at High Altitude among a Military Population with Frequent Migration: A Quasi Experimental Model for Investigating Spatial Causation

    PubMed Central

    Voss, Jameson D.; Allison, David B.; Webber, Bryant J.; Otto, Jean L.; Clark, Leslie L.

    2014-01-01

    We sought to evaluate whether residence at high altitude is associated with the development of obesity among those at increased risk of becoming obese. Obesity, a leading global health priority, is often refractory to care. A potentially novel intervention is hypoxia, which has demonstrated positive long-term metabolic effects in rats. Whether or not high altitude residence confers benefit in humans, however, remains unknown. Using a quasi-experimental, retrospective study design, we observed all outpatient medical encounters for overweight active component enlisted service members in the U.S. Army or Air Force from January 2006 to December 2012 who were stationed in the United States. We compared high altitude (>1.96 kilometers above sea level) duty assignment with low altitude (<0.98 kilometers). The outcome of interest was obesity related ICD-9 codes (278.00-01, V85.3x-V85.54) by Cox regression. We found service members had a lower hazard ratio (HR) of incident obesity diagnosis if stationed at high altitude as compared to low altitude (HR 0.59, 95% confidence interval [CI] 0.54–0.65; p<0.001). Using geographic distribution of obesity prevalence among civilians throughout the U.S. as a covariate (as measured by the Centers for Disease Control and Prevention and the REGARDS study) also predicted obesity onset among service members. In conclusion, high altitude residence predicts lower rates of new obesity diagnoses among overweight service members in the U.S. Army and Air Force. Future studies should assign exposure using randomization, clarify the mechanism(s) of this relationship, and assess the net balance of harms and benefits of high altitude on obesity prevention. PMID:24740173

  8. Lower obesity rate during residence at high altitude among a military population with frequent migration: a quasi experimental model for investigating spatial causation.

    PubMed

    Voss, Jameson D; Allison, David B; Webber, Bryant J; Otto, Jean L; Clark, Leslie L

    2014-01-01

    We sought to evaluate whether residence at high altitude is associated with the development of obesity among those at increased risk of becoming obese. Obesity, a leading global health priority, is often refractory to care. A potentially novel intervention is hypoxia, which has demonstrated positive long-term metabolic effects in rats. Whether or not high altitude residence confers benefit in humans, however, remains unknown. Using a quasi-experimental, retrospective study design, we observed all outpatient medical encounters for overweight active component enlisted service members in the U.S. Army or Air Force from January 2006 to December 2012 who were stationed in the United States. We compared high altitude (>1.96 kilometers above sea level) duty assignment with low altitude (<0.98 kilometers). The outcome of interest was obesity related ICD-9 codes (278.00-01, V85.3x-V85.54) by Cox regression. We found service members had a lower hazard ratio (HR) of incident obesity diagnosis if stationed at high altitude as compared to low altitude (HR 0.59, 95% confidence interval [CI] 0.54-0.65; p<0.001). Using geographic distribution of obesity prevalence among civilians throughout the U.S. as a covariate (as measured by the Centers for Disease Control and Prevention and the REGARDS study) also predicted obesity onset among service members. In conclusion, high altitude residence predicts lower rates of new obesity diagnoses among overweight service members in the U.S. Army and Air Force. Future studies should assign exposure using randomization, clarify the mechanism(s) of this relationship, and assess the net balance of harms and benefits of high altitude on obesity prevention.

  9. Aerodynamics of heat exchangers for high-altitude aircraft

    NASA Technical Reports Server (NTRS)

    Drela, Mark

    1996-01-01

    Reduction of convective beat transfer with altitude dictates unusually large beat exchangers for piston- engined high-altitude aircraft The relatively large aircraft drag fraction associated with cooling at high altitudes makes the efficient design of the entire heat exchanger installation an essential part of the aircraft's aerodynamic design. The parameters that directly influence cooling drag are developed in the context of high-altitude flight Candidate wing airfoils that incorporate heat exchangers are examined. Such integrated wing-airfoil/heat-exchanger installations appear to be attractive alternatives to isolated heat.exchanger installations. Examples are drawn from integrated installations on existing or planned high-altitude aircraft.

  10. [High altitude related health problems in travel medicine].

    PubMed

    Neumayr, Andreas

    2013-06-01

    Giving travel advice to travellers visiting high-altitude destinations around the globe is daily routine in travel clinics. However, with the classical focus on vaccinations, traveller's diarrhoea, mosquito protection and malaria prophylaxis, altitude-related health problems are often neglected at counselling. The importance to communicate these problems when giving travel advice is impressively reflected by the high prevalence of altitude-related health problems among tourists visiting high-lying tourist destinations. This article aims at providing an overview of core aspects of acclimatization to altitude and prevention of altitude-related health problems and to exemplarily address practice-oriented problem destinations.

  11. Hypoxia adaptations in the grey wolf (Canis lupus chanco) from Qinghai-Tibet Plateau.

    PubMed

    Zhang, Wenping; Fan, Zhenxin; Han, Eunjung; Hou, Rong; Zhang, Liang; Galaverni, Marco; Huang, Jie; Liu, Hong; Silva, Pedro; Li, Peng; Pollinger, John P; Du, Lianming; Zhang, XiuyYue; Yue, Bisong; Wayne, Robert K; Zhang, Zhihe

    2014-07-01

    The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau.

  12. Visual function at altitude under night vision assisted conditions.

    PubMed

    Vecchi, Diego; Morgagni, Fabio; Guadagno, Anton G; Lucertini, Marco

    2014-01-01

    Hypoxia, even mild, is known to produce negative effects on visual function, including decreased visual acuity and sensitivity to contrast, mostly in low light. This is of special concern when night vision devices (NVDs) are used during flight because they also provide poor images in terms of resolution and contrast. While wearing NVDs in low light conditions, 16 healthy male aviators were exposed to a simulated altitude of 12,500 ft in a hypobaric chamber. Snellen visual acuity decreased in normal light from 28.5 +/- 4.2/20 (normoxia) to 37.2 +/- 7.4/20 (hypoxia) and, in low light, from 33.8 +/- 6.1/20 (normoxia) to 42.2 +/- 8.4/20 (hypoxia), both at a significant level. An association was found between blood oxygen saturation and visual acuity without significance. No changes occurred in terms of sensitivity to contrast. Our data demonstrate that mild hypoxia is capable of affecting visual acuity and the photopic/high mesopic range of NVD-aided vision. This may be due to several reasons, including the sensitivity to hypoxia of photoreceptors and other retinal cells. Contrast sensitivity is possibly preserved under NVD-aided vision due to its dependency on the goggles' gain.

  13. Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

    PubMed Central

    2016-01-01

    ABSTRACT In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)–O2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb–O2 affinity should be expected to improve tissue O2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O2 loading and peripheral O2 unloading. Theoretical results indicate that the optimal Hb–O2 affinity varies as a non-linear function of environmental O2 availability, and the threshold elevation at which an increased Hb–O2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O2 equilibration at the blood–gas interface is limited by the kinetics of O2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb–O2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb–O2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb–O2 affinity and native elevation in birds. Evolved changes in Hb function in high-altitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates. PMID:27802149

  14. Hemoglobin-oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

    PubMed

    Storz, Jay F

    2016-10-15

    In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)-O 2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb-O 2 affinity should be expected to improve tissue O 2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O 2 loading and peripheral O 2 unloading. Theoretical results indicate that the optimal Hb-O 2 affinity varies as a non-linear function of environmental O 2 availability, and the threshold elevation at which an increased Hb-O 2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O 2 equilibration at the blood-gas interface is limited by the kinetics of O 2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb-O 2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb-O 2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb-O 2 affinity and native elevation in birds. Evolved changes in Hb function in high-altitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates. © 2016. Published by The Company of Biologists Ltd.

  15. High-altitude cerebral oedema mimicking stroke.

    PubMed

    Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

    2014-03-26

    High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

  16. Adaptation of aeronautical engines to high altitude flying

    NASA Technical Reports Server (NTRS)

    Kutzbach, K

    1923-01-01

    Issues and techniques relative to the adaptation of aircraft engines to high altitude flight are discussed. Covered here are the limits of engine output, modifications and characteristics of high altitude engines, the influence of air density on the proportions of fuel mixtures, methods of varying the proportions of fuel mixtures, the automatic prevention of fuel waste, and the design and application of air pressure regulators to high altitude flying. Summary: 1. Limits of engine output. 2. High altitude engines. 3. Influence of air density on proportions of mixture. 4. Methods of varying proportions of mixture. 5. Automatic prevention of fuel waste. 6. Design and application of air pressure regulators to high altitude flying.

  17. Syndrome of acute anxiety among marines after recent arrival at high altitude.

    PubMed

    Sracic, Michael K; Thomas, Darren; Pate, Allen; Norris, Jacob; Norman, Marc; Gertsch, Jeffrey H

    2014-05-01

    Management of mental health is critical for maintenance of readiness in austere military environments. Emerging evidence implicates hypoxia as an environmental trigger of anxiety spectrum symptomatology. One thousand thirty-six unacclimatized infantry Marines ascended from sea level to the Marine Corps Mountain Warfare Training Center (2,061-3,383 m) for a 30-day exercise. Within the first 6 days of training, 7 servicemen presented with severe, acute anxiety/panic with typical accompanying signs of sympathetic activation and no classic symptoms of acute mountain sickness (including headache). Four had a history of well-controlled psychiatric diagnoses. Invariably, cardiopulmonary and neurological evaluations were unrevealing, and acute cardiopulmonary events were excluded within limits of expeditionary diagnostic capabilities. All patients responded clinically to oxygen, rest, and benzodiazepines, returning to baseline function the same day. The unexpected onset of 7 cases of acute anxiety symptomatology coincident with recent arrival at moderate-to-high altitudes represents a highly unusual incidence and temporal distribution, suggestive of hypobaric hypoxemia as the proximal cause. We propose acute hypoxic physiological anxiety (AHPA) as a unique member of the spectrum of altitude-associated neurological disorders. Recognition of AHPA is particularly relevant in a military population; warfighters with anxiety spectrum diagnoses may have a recognizable and possibly preventable vulnerability. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  18. Oxygen transport in blood at high altitude: role of the hemoglobin-oxygen affinity and impact of the phenomena related to hemoglobin allosterism and red cell function.

    PubMed

    Samaja, Michele; Crespi, Tiziano; Guazzi, Marco; Vandegriff, Kim D

    2003-10-01

    Altitude hypoxia is a major challenge to the blood O2 transport system, and adjustments of the blood-O2 affinity might contribute significantly to hypoxia adaptation. In principle, lowering the blood-O2 affinity is advantageous because it lowers the circulatory load required to assure adequate tissue oxygenation up to a threshold corresponding to about 5,000 m altitude, whereas at higher altitudes an increased blood-O2 affinity appears more advantageous. However, the rather contradictory experimental evidence raises the question whether other factors superimpose on the apparent changes of the blood-O2 affinity. The most important of these are as follows: (1) absolute temperature and temperature gradients within the body; (2) the intracapillary Bohr effect; (3) the red cell population heterogeneity in terms of O2 affinity; (4) control of altitude alkalosis; (5) the possible role of hemoglobin as a carrier of the vasodilator nitric oxide; (6) the effect of varied red cell transit times through the capillaries.

  19. Dark adaptation during systemic hypoxia induced by chronic respiratory insufficiency.

    PubMed

    Thylefors, Joakim; Piitulainen, Eeva; Havelius, Ulf

    2009-03-01

    To investigate dark adaptation during hypoxia in patients with chronic respiratory failure. At three visits, dark adaptation was recorded by computerized dark adaptometry in 13 patients with chronic respiratory insufficiency treated by long-term oxygen therapy. At visits 1 and 3, the patients were administered their usual oxygen supplement. At visit 2, no oxygen was given. At each visit, an analysis of arterial blood gases measured pH, partial pressure of O(2) (Pao(2)), partial pressure of CO(2) (Paco(2)), base excess (BE), standard bicarbonate (HCO(3)), and arterial oxygen saturation. Pulse oximetry (POX) was also recorded. Significant differences were recorded between visits 1 and 2 and between visits 2 and 3 for Pao(2), arterial oxygen saturation, and POX; no differences were found for pH, Paco(2), BE, or HCO(3). No differences were seen between visits 1 and 3 for any of the laboratory parameters. All patients had normal and unchanged dark adaptation at the three visits. Hypoxia in chronic respiratory insufficiency was associated with normal dark adaptation, in contrast to hypoxia in healthy persons at high altitudes, which is known to produce impaired dark adaptation. The result may partly reflect the influence of Paco(2) on the lumen of choroidal and retinal vessels. At high altitudes, with hypocapnic vasoconstriction the oxygen supply to the retina is further compromised, resulting in reduced dark adaptation. The authors hypothesize that respiratory insufficiency with hypercapnia or normocapnia will have larger choroidal and retinal vessel lumens, added to by further dilation of retinal vessels during hypoxia. The tentative net effect would be preserved dark adaptation.

  20. The effect of altitude on cycling performance: a challenge to traditional concepts.

    PubMed

    Hahn, A G; Gore, C J

    2001-01-01

    Acute exposure to moderate altitude is likely to enhance cycling performance on flat terrain because the benefit of reduced aerodynamic drag outweighs the decrease in maximum aerobic power [maximal oxygen uptake (VO2max)]. In contrast, when the course is mountainous, cycling performance will be reduced at moderate altitude. Living and training at altitude, or living in an hypoxic environment (approximately 2500 m) but training near sea level, are popular practices among elite cyclists seeking enhanced performance at sea level. In an attempt to confirm or refute the efficacy of these practices, we reviewed studies conducted on highly-trained athletes and, where possible, on elite cyclists. To ensure relevance of the information to the conditions likely to be encountered by cyclists, we concentrated our literature survey on studies that have used 2- to 4-week exposures to moderate altitude (1500 to 3000 m). With acclimatisation there is strong evidence of decreased production or increased clearance of lactate in the muscle, moderate evidence of enhanced muscle buffering capacity (beta m) and tenuous evidence of improved mechanical efficiency (ME) of cycling. Our analysis of the relevant literature indicates that, in contrast to the existing paradigm, adaptation to natural or simulated moderate altitude does not stimulate red cell production sufficiently to increase red cell volume (RCV) and haemoglobin mass (Hb(mass)). Hypoxia does increase serum erthyropoietin levels but the next step in the erythropoietic cascade is not clearly established; there is only weak evidence of an increase in young red blood cells (reticulocytes). Moreover, the collective evidence from studies of highly-trained athletes indicates that adaptation to hypoxia is unlikely to enhance sea level VO2max. Such enhancement would be expected if RCV and Hb(mass) were elevated. The accumulated results of 5 different research groups that have used controlled study designs indicate that continuous

  1. DLR HABLEG- High Altitude Balloon Launched Experimental Glider

    NASA Astrophysics Data System (ADS)

    Wlach, S.; Schwarzbauch, M.; Laiacker, M.

    2015-09-01

    The group Flying Robots at the DLR Institute of Robotics and Mechatronics in Oberpfaffenhofen conducts research on solar powered high altitude aircrafts. Due to the high altitude and the almost infinite mission duration, these platforms are also denoted as High Altitude Pseudo-Satellites (HAPS). This paper highlights some aspects of the design, building, integration and testing of a flying experimental platform for high altitudes. This unmanned aircraft, with a wingspan of 3 m and a mass of less than 10 kg, is meant to be launched as a glider from a high altitude balloon in 20 km altitude and shall investigate technologies for future large HAPS platforms. The aerodynamic requirements for high altitude flight included the development of a launch method allowing for a safe transition to horizontal flight from free-fall with low control authority. Due to the harsh environmental conditions in the stratosphere, the integration of electronic components in the airframe is a major effort. For regulatory reasons a reliable and situation dependent flight termination system had to be implemented. In May 2015 a flight campaign was conducted. The mission was a full success demonstrating that stratospheric research flights are feasible with rather small aircrafts.

  2. Ageing and cardiorespiratory response to hypoxia.

    PubMed

    Lhuissier, François J; Canouï-Poitrine, Florence; Richalet, Jean-Paul

    2012-11-01

    The risk of severe altitude-induced diseases is related to ventilatory and cardiac responses to hypoxia and is dependent on sex, age and exercise training status. However, it remains unclear how ageing modifies these physiological adaptations to hypoxia. We assessed the physiological responses to hypoxia with ageing through a cross-sectional 20 year study including 4675 subjects (2789 men, 1886 women; 14-85 years old) and a longitudinal study including 30 subjects explored at a mean 10.4 year interval. The influence of sex, training status and menopause was evaluated. The hypoxia-induced desaturation and the ventilatory and cardiac responses to hypoxia at rest and exercise were measured. In men, ventilatory response to hypoxia increased (P < 0.002), while desaturation was less pronounced (P < 0.001) with ageing. Cardiac response to hypoxia was blunted with ageing in both sexes (P < 0.001). Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with ageing. These adaptive responses were less pronounced or absent in post-menopausal women (P < 0.01). At exercise, desaturation was greater in trained subjects but cardiac and ventilatory responses to hypoxia were preserved by training, especially in elderly people. In conclusion, respiratory response to hypoxia and blood oxygenation improve with ageing in men while cardiac response is blunted with ageing in both sexes. Training aggravates desaturation at exercise in hypoxia, improves the ventilatory response and limits the ageing-induced blunting of cardiac response to hypoxia. Training limits the negative effects of menopause in cardiorespiratory adaptations to hypoxia.

  3. [Relationship between occupational stress and working ability of workers in a petroleum processing enterprise in high altitude area].

    PubMed

    Ma, X M; Kang, H L; Shi, C B; Li, Y; Wu, Y F; Liu, Z H; Wang, G; Lei, H Y

    2017-12-20

    Objective: To investigate the relationship between occupational stress and working ability of workers in a petroleum processing enterprise in a high altitude area. Methods: A total of 728 workers in a petroleum processing enterprise at an altitude of 2850 m were subjected to a survey using Occupational Stress Inventory (OSI) , Work Ability Index (WAI) Scale, Occupational Role Questionnaire (ORQ) , Personal Strain Questionnaire (PSQ) , and Personal Resource Questionnaire (PRQ) from May 2014 to August 2016. Results: Of the 728 workers, 55 (7.6%) had a poor working ability, moderate in 262 (35.9%) , and good in 411 (56.5%). There were significant differences in WAI between the workers with different types of work, sexes, ages, and working years ( P <0.05). There was a significant difference in WAI between different occupational stress groups ( P <0.05). WAI was negatively correlated with ORQ score and PSQ score ( r (s)=-0.387, P <0.05; r (s)=-0.467, P <0.05) and positively correlated with PRQ score ( r (s)=0.343, P <0.05). The multiple linear regression analysis showed that high ORQ score and PSQ score were the inhibitory factors for high WAI ( B =-0.058; B =-0.082) and high PRQ score was a contributing factor for high WAI ( B =0.029) . Conclusion: Occupational stress is an influencing factor for the working ability of workers in the petroleum processing enterprise in the high altitude area. Hypoxia in high altitude area may further reduce the working ability. In order to reduce occupational stress and improve work ability, it should be considered to strengthen skills training, improve the working environment, and pay attention to mental health.

  4. A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

    PubMed Central

    Lippold, Sebastian; de Filippo, Cesare; Tang, Kun; López Herráez, David; Li, Jing; Stoneking, Mark

    2015-01-01

    Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways

  5. Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated Ca2+ sparks in fetal sheep pulmonary arterial myocytes

    PubMed Central

    Hadley, Scott R.; Blood, Quintin; Rubalcava, Monica; Waskel, Edith; Lumbard, Britney; Le, Petersen; Longo, Lawrence D.; Buchholz, John N.

    2012-01-01

    Ca2+ sparks are fundamental Ca2+ signaling events arising from ryanodine receptor (RyR) activation, events that relate to contractile and dilatory events in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult animals. Because RyRs are important to pulmonary vascular reactivity and reactivity changes with ontogeny and LTH we tested the hypothesis that RyR-generated Ca2+ signals are more active before birth and that LTH suppresses these responses. We examined these hypotheses by performing confocal imaging of myocytes in living arteries and by performing wire myography studies. Pulmonary arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal imaging demonstrated preservation of the distance between the sarcoplasmic reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased global Ca2+ waves and Ca2+ spark activity, with sparks becoming larger, wider, and slower. LTH preferentially depressed Ca2+ spark activity in immature pulmonary arterial myocytes, and these sparks were smaller, wider, and slower. LTH also suppressed caffeine-elicited contraction in fetal PA but augmented contraction in the newborn and adult. The influence of both ontogeny and LTH on RyR-dependent cell excitability shed new light on the therapeutic potential of these channels for the treatment of pulmonary vascular disease in newborns as well as adults. PMID:22962012

  6. Physiological implications of altitude training for endurance performance at sea level: a review.

    PubMed Central

    Bailey, D M; Davies, B

    1997-01-01

    Acclimatisation to environmental hypoxia initiates a series of metabolic and musculocardio-respiratory adaptations that influence oxygen transport and utilisation, or better still, being born and raised at altitude, is necessary to achieve optimal physical performance at altitude, scientific evidence to support the potentiating effects after return to sea level is at present equivocal. Despite this, elite athletes continue to spend considerable time and resources training at altitude, misled by subjective coaching opinion and the inconclusive findings of a large number of uncontrolled studies. Scientific investigation has focused on the optimisation of the theoretically beneficial aspects of altitude acclimatisation, which include increases in blood haemoglobin concentration, elevated buffering capacity, and improvements in the structural and biochemical properties of skeletal muscle. However, not all aspects of altitude acclimatisation are beneficial; cardiac output and blood flow to skeletal muscles decrease, and preliminary evidence has shown that hypoxia in itself is responsible for a depression of immune function and increased tissue damage mediated by oxidative stress. Future research needs to focus on these less beneficial aspects of altitude training, the implications of which pose a threat to both the fitness and the health of the elite competitor. Paul Bert was the first investigator to show that acclimatisation to a chronically reduced inspiratory partial pressure of oxygen (P1O2) invoked a series of central and peripheral adaptations that served to maintain adequate tissue oxygenation in healthy skeletal muscle, physiological adaptations that have been subsequently implicated in the improvement in exercise performance during altitude acclimatisation. However, it was not until half a century later that scientists suggested that the additive stimulus of environmental hypoxia could potentially compound the normal physiological adaptations to endurance

  7. Return to Activity at Altitude After High-Altitude Illness

    PubMed Central

    DeWeber, Kevin; Scorza, Keith

    2010-01-01

    Context: Sports and other activities at high altitude are popular, yet they pose the unique risk for high-altitude illness (HAI). Once those who have suffered from a HAI recover, they commonly desire or need to perform the same activity at altitude in the immediate or distant future. Evidence Acquisition: As based on key text references and peer-reviewed journal articles from a Medline search, this article reviews the pathophysiology and general treatment principles of HAI. Results: In addition to the type of HAI experienced and the current level of recovery, factors needing consideration in the return-to-play plan include physical activity requirements, flexibility of the activity schedule, and available medical equipment and facilities. Most important, adherence to prudent acclimatization protocols and gradual ascent recommendations (when above 3000 m, no more than 600-m net elevation gain per day, and 1 rest day every 1 to 2 ascent days) is powerful in its preventive value and thus strongly recommended. When these are not practical, prophylactic medications (acetazolamide, dexamethasone, salmeterol, nifedipine, or phosphodiesterase inhibitors, depending on the type of prior HAI) may be prescribed and can reduce the risk of illness. Athletes with HAI should be counseled that physical and mental performance may be adversely affected if activity at altitude continues before recovery is complete and that there is a risk of progression to a more serious HAI. Conclusion: With a thoughtful plan, most recurrent HAI in athletes can be prevented. PMID:23015950

  8. The effect of hypoxia on the critical flicker fusion threshold in pilots.

    PubMed

    Truszczyński, Olaf; Wojtkowiak, Mieczysław; Biernacki, Marcin; Kowalczuk, Krzysztof

    2009-01-01

    Human reactions to environmental changes have been the subject of numerous investigations related to pathophysiology, aviation psychology, aviation, and sports. The present study aimed at evaluating the perception of light stimulus via the Critical Flicker Fusion threshold (CFF) measurements among aviation pilots. The study was carried out under hypoxic conditions corresponding to 5000 m altitude, for a period of 30 min, without the use of supplemental oxygen. Fourteen volunteer pilots, 23-30 years of age, were examined in the hypobaric chamber (HC). The measurements were performed at normobaria and at the initial and final phase of hypoxia. Heart rate (HR) and blood oxygen saturation (SaO2) were monitored. The high altitude hypoxia was found to produce a decrease in the CFF threshold F(3.39) = 3.207, p < 0.05, and SaO2 F(3.39) = 52.651, p < 0.001, as well as HR increase F(3.39) = 7.356, p < 0.001. The results indicate that the higher the decrease in SaO2 under hypoxic conditions, the higher the decrease in CFF r = .567 p < 0.05. Likewise, the higher the increase in HR, the higher the decrease in CFF r = -0.491 p < 0.05. Under hypoxic conditions, the perceptual ability of the pilots is gradually decreasing. This has been confirmed by the findings of the physiological examinations. The authors express an opinion that it would be advisable to introduce CFF measurement into the hypobaric chamber tests as it allows individual assessment of the pilot's perceptual ability under conditions of incomplete physiological compensation of the high altitude hypoxia.

  9. High altitude flying

    NASA Technical Reports Server (NTRS)

    King, Paul B; Carroll, Thomas

    1924-01-01

    This note investigates the effect of high altitude or low atmospheric pressure upon the operation of an engine and the effect of the low pressure and lack of oxygen and of the very low temperatures upon the pilot and upon the performance of the airplane itself.

  10. Subjective and objective convergence of the eyes at simulated altitude of 18,000 feet preceded by short-term exposure to heat stress.

    PubMed

    Sinha, Biswajit; Dubey, D K

    2014-01-01

    Armed forces personnel including military aviators are quite often exposed concurrently to various environmental stressors like high environmental temperature and hypoxia. Literatures have suggested that exposure to one environmental stressor may modify the physiological response on subsequent exposure to same or different stressor. The present study was undertaken to investigate the impact of cross tolerance between two environmental stressors of aviation (heat and hypoxia) in ten healthy adult males in a simulated altitude chamber in a within subject experimental study. They were assessed for their convergence ability of the eyes at ground and at simulated altitude of 18,000 ft with or without pre-exposure to heat stress. Subjective convergence at simulated altitude of 18,000 ft did not show any improvement following pre-exposure to heat stress. Objective convergence was improved following pre-exposure to heat stress and was found to be 10.76 cm and 9.10 cm without and with heat stress respectively at simulated altitude of 18,000 ft. Improved objective convergence at high altitude as a result of pre-exposure to heat stress is indicative of better ocular functions. This might benefit aviators while flying at hypoxic condition.

  11. High altitude pulmonary oedema (HAPE) in an Indian pilgrim.

    PubMed

    Panthi, Sagar; Basnyat, Buddha

    2013-11-01

    Increasing number of Hindu pilgrims visit the Himalayas where some of them suffer from high altitude illness including the life threatening forms, high altitude pulmonary oedema (HAPE) and high altitude cerebral oedema. Compared to tourists and trekkers, pilgrims are usually ignorant about altitude illness. This is a case of a pilgrim who suffered from HAPE on his trip to Kailash-Mansarovar and is brought to a tertiary level hospital in Kathmandu. This report emphasises on how to treat a patient with HAPE, a disease which is increasingly being seen in the high altitude pilgrim population.

  12. The Impact of Altitude on Sleep-Disordered Breathing in Children Dwelling at High Altitude: A Crossover Study.

    PubMed

    Hughes, Benjamin H; Brinton, John T; Ingram, David G; Halbower, Ann C

    2017-09-01

    Sleep-disordered breathing (SDB) is prevalent among children and is associated with adverse health outcomes. Worldwide, approximately 250 million individuals reside at altitudes higher than 2000 meters above sea level (masl). The effect of chronic high-altitude exposure on children with SDB is unknown. This study aims to determine the impact of altitude on sleep study outcomes in children with SDB dwelling at high altitude. A single-center crossover study was performed to compare results of high-altitude home polysomnography (H-PSG) with lower altitude laboratory polysomnography (L-PSG) in school-age children dwelling at high altitude with symptoms consistent with SDB. The primary outcome was apnea-hypopnea index (AHI), with secondary outcomes including obstructive AHI; central AHI; and measures of oxygenation, sleep quality, and pulse rate. Twelve participants were enrolled, with 10 included in the final analysis. Median altitude was 1644 masl on L-PSG and 2531 masl on H-PSG. Median AHI was 2.40 on L-PSG and 10.95 on H-PSG. Both obstructive and central respiratory events accounted for the difference in AHI. Oxygenation and sleep fragmentation were worse and pulse rate higher on H-PSG compared to L-PSG. These findings reveal a clinically substantial impact of altitude on respiratory, sleep, and cardiovascular outcomes in children with SDB who dwell at high altitude. Within this population, L-PSG underestimates obstructive sleep apnea and central sleep apnea compared to H-PSG. Given the shortage of high-altitude pediatric sleep laboratories, these results suggest a role for home sleep apnea testing for children residing at high altitude. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  13. Detection of ocean color changes from high altitudes

    NASA Technical Reports Server (NTRS)

    Hovis, W. A.; Forman, M. L.; Blaine, L. R.

    1973-01-01

    The detection of ocean color changes, thought to be due to chlorophyll concentrations and gelbstoffe variations, is attempted from high altitude (11.3km) and low altitude (0.3km). The atmospheric back scattering is shown to reduce contrast, but not sufficiently to obscure color change detection at high altitudes.

  14. A High-Altitude Site Survey for SOFIA

    NASA Astrophysics Data System (ADS)

    Haas, Michael R.; Pfister, Leonhard

    1998-03-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a modified Boeing 747-SP equipped with a 2.5 m telescope dedicated to astronomical research. Currently under joint development by the US (NASA) and Germany (DLR), it is scheduled to begin operations in late 2001. The ability of SOFIA to carry out its mission will depend strongly on the meteorological conditions at and above flight altitudes in the vicinity of its home base. The most important meteorological factors are the frequency of high-altitude clouds and the magnitude of the water vapor overburdens. This paper performs a high-altitude site survey by gathering together the best available meteorological data, defining metrics, and evaluating them for a variety of sites. These metrics are found to corroborate past airborne experience and to be consistent with well-known global circulation patterns, convection, and upper tropospheric dynamics. They indicate that there are significant variations in the weather at SOFIA flight altitudes. Particularly in summer, some continental US sites are shown to be worse than Hawaii, where high-altitude cirrus clouds and the associated moisture have historically caused significant losses in the amount and quality of the astronomical data collected by NASA's Kuiper Airborne Observatory. SOFIA's planned home base, Moffett Field, CA, is found to have excellent high-altitude weather and to be one of the best continental US sites.

  15. Altitude negates the benefits of aerobic training on the vascular adaptations in rats.

    PubMed

    Reboul, Cyril; Tanguy, Stephane; Dauzat, Michel; Obert, Philippe

    2005-06-01

    This study questioned the effect of living and training at moderate altitude on aortic vasoreactivity. Considering that chronic hypoxia exposure and endurance training are able to generate opposite effects on the systemic vascular reactivity, it was hypothesized that endurance training benefits on the vascular function could be limited by chronic hypoxia. Sea-level native rats were randomly assigned to N (living in normoxia), NT (living and training 5 d.wk for 5 wk in normoxia), CH (living in hypoxia, 2800 m), and CHT (living and training 5 d.wk for 5 wk in hypoxia, 2800 m) groups. Concentration response curves to epinephrine, norepinephrine, endothelin-1, acetylcholine, and sodium nitro-prusside were assessed on aortic isolated rings. Left ventricular resting and maximal (during Tyrode's infusion) stroke volumes were evaluated by Doppler-echocardiography and used as indexes of chronic aortic volume overload. The main finding was that favorable aortic vasoreactivity adaptations consecutive to sea-level training were not observed when training was conducted at altitude. An improvement in the endothelium-dependent vasorelaxation (maximal relaxation, R(max), N = 60.4 +/- 10.0 vs NT = 91.7 +/- 3.2%; P < 0.05) and a reduced sensitivity to ET-1 were observed in NT rats. Such an enhancement in endothelium-dependent vasorelaxation was not found in CHT rats (R(max): 48.4 +/- 7.8%). Moreover, a higher sensitivity to ET-1 was reported in this group. Altitude-induced limitation in aortic blood flow and shear stress could play a major role in the explanation of these specific altitude-training adaptations. If extrapolated to the peripheral vascular bed, our results have practical significance for aerobic performance as aortic vasoreactivity adaptations after altitude training could contribute to limit blood delivery to exercising muscles.

  16. The sleep of elite athletes at sea level and high altitude: a comparison of sea-level natives and high-altitude natives (ISA3600).

    PubMed

    Roach, Gregory D; Schmidt, Walter F; Aughey, Robert J; Bourdon, Pitre C; Soria, Rudy; Claros, Jesus C Jimenez; Garvican-Lewis, Laura A; Buchheit, Martin; Simpson, Ben M; Hammond, Kristal; Kley, Marlen; Wachsmuth, Nadine; Gore, Christopher J; Sargent, Charli

    2013-12-01

    Altitude exposure causes acute sleep disruption in non-athletes, but little is known about its effects in elite athletes. The aim of this study was to examine the effects of altitude on two groups of elite athletes, that is, sea-level natives and high-altitude natives. Sea-level natives were members of the Australian under-17 soccer team (n=14). High-altitude natives were members of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19 nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on every day/night using activity monitors. The Australians' sleep was shorter, and of poorer quality, on the first night at altitude compared with sea level. Sleep quality returned to normal by the end of the first week at altitude, but sleep quantity had still not stabilised at its normal level after 2 weeks. The quantity and quality of sleep obtained by the Bolivians was similar, or greater, on all nights at altitude compared with sea level. The Australians tended to obtain more sleep than the Bolivians at sea level and altitude, but the quality of the Bolivians' sleep tended to be better than that of the Australians at altitude. Exposure to high altitude causes acute and chronic disruption to the sleep of elite athletes who are sea-level natives, but it does not affect the sleep of elite athletes who are high-altitude natives.

  17. Associations Between Arterial Oxygen Saturation, Body Size and Limb Measurements Among High-Altitude Andean Children

    PubMed Central

    Pomeroy, Emma; Stock, Jay T; Stanojevic, Sanja; Miranda, J Jaime; Cole, Tim J; Wells, Jonathan CK

    2013-01-01

    Objectives The relative influences of hypoxia and other environmental stressors on growth at altitude remain unclear. Previous work demonstrated an association between peripheral arterial oxygen saturation (SpO2) and anthropometry (especially tibia length) among Tibetan and Han children at altitude. We investigated whether similar associations exist among Andeans, and the patterning of associations between SpO2 and anthropometry. Methods Stature, head-trunk height, total upper and lower limb lengths, zeugopod (ulna and tibia) and autopod (hand and foot) lengths were measured in Peruvian children (0.5–14 years) living at >3000 m altitude. SpO2 was measured by pulse oximetry. Anthropometry was converted to internal z scores. Correlation and multiple regression were used to examine associations between anthropometry z scores and SpO2, altitude, or SpO2 adjusted for altitude since altitude is a major determinant of variation in SpO2. Results SpO2 and altitude show weak, significant correlations with zeugopod length z scores and still weaker significant correlations with total upper and lower limb length z scores. Correlations with z scores for stature, head-trunk height, or autopod lengths are not significant. Adjusted for altitude, there is no significant association between anthropometry and SpO2. Conclusions Associations between SpO2 or altitude and total limb and zeugopod length z scores exist among Andean children. However, the relationships are relatively weak, and while the relationship between anthropometry and altitude may be partly mediated by SpO2, other factors that covary with altitude (e.g., socioeconomic status, health) are likely to influence anthropometry. The results support suggestions that zeugopod lengths are particularly sensitive to environmental stressors. Am. J. Hum. Biol., 25:629–636, 2013. © 2013 Wiley Periodicals, Inc. PMID:23904412

  18. Changes in transthoracic electrical impedance at high altitude.

    PubMed

    Hoon, R S; Balasubramanian, V; Tiwari, S C; Mathew, O P; Behl, A; Sharma, S C; Chadha, K S

    1977-01-01

    Mean transthoracic electrical impedance (impedance) which is inversely related to intrathoracic extravascular fluid volume was measured in 121 normal healthy volunteers at sea-level and at 3658 metres altitude. Fifty (group A) reached the high altitude location after an hour's journey in a pressurised aircraft. Twenty-five (group D) underwent slow road ascent including acclimatisation en route. Thirty permanent residents (group B) and 16 temporary residents at high altitude (group C) were also studied. Serial studies in the 30 subjects of group A who developed symptoms of high altidue sickness showed a significant decrease of impedance up to the fourth day of exposure to high altitude which later returned to normal. The 4 volunteers who developed severe symptoms showed the largest drop in impedance. A case of acute pulmonary oedema developing at 4300 metres showed an impedance value of 24-1 ohms on admission. After effective treatment the impedance increased by 11-9 to 36-0 ohms. Twenty asymptomatic subjects of group A and 25 of group D showed a small average increase in impedance values at high altitude. These obstructions suggest that measurement of transthoracic electrical impedance may be a valuable means of detecting incipient high altitude pulmonary oedema.

  19. Extreme altitude: words from on high.

    PubMed

    Lankford, Harvey V

    2014-09-01

    Medical science has its own objective language for describing the effects of high altitude. Mountaineers' words and metaphors tell the story with subjectivity and feeling. This essay will include only limited physiology about lowlanders and high altitude. Instead, the focus will be literary, using the quotations of 20th-century mountaineers and mountaineer physicians to provide color commentary about the hardship. These are Words From on High. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  20. Pulmonary Adaptation to High Altitude.

    DTIC Science & Technology

    1983-08-12

    base status, cerebral hypoxia,.periodic. breathing in sleep, exercise gas exchange, * respiratory mnuscle fatigue. .-. A4N~rea~.&P ol nftw-"Nyr OMI... respiratory muscle’ metboYi L * morphology in the rat; and the effects of lg-emyoxaand differint levels of hypoxia on venitilation and periodic breathing...34 hypothesis. 5. The rat appears to be a good model for the study of respiratory muscle metabolism during exercise and in chronic hypoxia. Studies on both of

  1. The sleep of elite athletes at sea level and high altitude: a comparison of sea-level natives and high-altitude natives (ISA3600)

    PubMed Central

    Roach, Gregory D; Schmidt, Walter F; Aughey, Robert J; Bourdon, Pitre C; Soria, Rudy; Claros, Jesus C Jimenez; Garvican-Lewis, Laura A; Buchheit, Martin; Simpson, Ben M; Hammond, Kristal; Kley, Marlen; Wachsmuth, Nadine; Gore, Christopher J; Sargent, Charli

    2013-01-01

    Background Altitude exposure causes acute sleep disruption in non-athletes, but little is known about its effects in elite athletes. The aim of this study was to examine the effects of altitude on two groups of elite athletes, that is, sea-level natives and high-altitude natives. Methods Sea-level natives were members of the Australian under-17 soccer team (n=14). High-altitude natives were members of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19 nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on every day/night using activity monitors. Results The Australians’ sleep was shorter, and of poorer quality, on the first night at altitude compared with sea level. Sleep quality returned to normal by the end of the first week at altitude, but sleep quantity had still not stabilised at its normal level after 2 weeks. The quantity and quality of sleep obtained by the Bolivians was similar, or greater, on all nights at altitude compared with sea level. The Australians tended to obtain more sleep than the Bolivians at sea level and altitude, but the quality of the Bolivians’ sleep tended to be better than that of the Australians at altitude. Conclusions Exposure to high altitude causes acute and chronic disruption to the sleep of elite athletes who are sea-level natives, but it does not affect the sleep of elite athletes who are high-altitude natives. PMID:24282197

  2. Effects of Ascent to High Altitude on Human Antimycobacterial Immunity

    PubMed Central

    Aldridge, Robert W.; Siedner, Mark J.; Necochea, Alejandro; Leybell, Inna; Valencia, Teresa; Herrera, Beatriz; Wiles, Siouxsie; Friedland, Jon S.; Gilman, Robert H.; Evans, Carlton A.

    2013-01-01

    Background Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity. Methods Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants’ whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants’ whole blood versus positive-control culture broth and versus negative-control plasma. Results Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents. Conclusions An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or

  3. Propofol-fentanyl anaesthesia at high altitude: anaesthetic requirements and haemodynamic variations when compared with anaesthesia at low altitude.

    PubMed

    Puri, G D; Jayant, A; Dorje, M; Tashi, M

    2008-03-01

    There are few published accounts of anaesthesia delivery at high altitude. Natives at high altitude are known to have altered cardiorespiratory reserve. This study seeks to demonstrate the safety of propofol-fentanyl anaesthesia at high altitude titrated to the bispectral index (BIS) (3505 metres above sea level) in native highlanders. It also shows the differential effects of anaesthesia and surgery on the haemodynamics of such individuals as compared with individuals living at low altitude. Fifteen consenting adults scheduled to undergo general surgical/orthopaedic procedures under general anaesthesia using fentanyl, and propofol infusions titrated to the BIS along with nitrous oxide in oxygen after intubation, were recruited in the high-altitude arm. Their anaesthesia record was compared with retrospective data from low altitude with respect to anaesthetic requirements, recovery after anaesthesia and the haemodynamic responses to surgical stress. The high-altitude dwellers required significantly larger doses of propofol at anaesthetic induction (2.31+/-0.64 vs. 1.41+/-0.24 mg/kg, P<0.0001) and thereafter to maintain designated BIS than their low-altitude counterparts (6.22+/-1.14 vs. 4.61+/-1.29 mg/kg/h, P<0.01). They, however, had uneventful and short recovery times. The high-altitude population also had significantly lower baseline heart rates (72+/-9.83 vs. 88+/-12.1, P<0.04) as also the heart rate responses to noxious stimulation such as direct laryngoscopy or skin incision (P<0.04, P<0.005, respectively). High-altitude dwellers require significantly larger amounts of intravenous anaesthetic propofol. Heart rate at rest as also the heart rate responses to surgical stress were significantly attenuated at high altitude.

  4. Sonic Thermometer for High-Altitude Balloons

    NASA Technical Reports Server (NTRS)

    Bognar, John

    2012-01-01

    The sonic thermometer is a specialized application of well-known sonic anemometer technology. Adaptations have been made to the circuit, including the addition of supporting sensors, which enable its use in the high-altitude environment and in non-air gas mixtures. There is a need to measure gas temperatures inside and outside of superpressure balloons that are flown at high altitudes. These measurements will allow the performance of the balloon to be modeled more accurately, leading to better flight performance. Small thermistors (solid-state temperature sensors) have been used for this general purpose, and for temperature measurements on radiosondes. A disadvantage to thermistors and other physical (as distinct from sonic) temperature sensors is that they are subject to solar heating errors when they are exposed to the Sun, and this leads to issues with their use in a very high-altitude environment

  5. The pulmonary circulation of some domestic animals at high altitude

    NASA Astrophysics Data System (ADS)

    Anand, I.; Heath, D.; Williams, D.; Deen, M.; Ferrari, R.; Bergel, D.; Harris, P.

    1988-03-01

    Pulmonary haemodynamics and the histology of the pulmonary vasculature have been studied at high altitude in the yak, in interbreeds between yaks and cattle, and in domestic goats and sheep indigenous to high altitudes together with crosses between them and low-altitude strains. Cattle at high altitude had a higher pulmonary arterial pressure than cattle at low altitude. The yak and two interbreeds with cattle (dzos and stols) had a low pulmonary arterial pressure compared with cattle, while the medial thickness of the small pulmonary arteries was less than would be expected in cattle, suggesting that the yak has a low capacity for hypoxic pulmonary vasoconstriction and that this characteristic is transmitted genetically. Goats and sheep showed haemodynamic evidence of a limited response of the pulmonary circulation to high altitude, but no evidence that the high altitude breeds had lost this response. There were no measurable differences in the thickness of the media of the small pulmonary arteries between high- and low-altitude breeds of goats and sheep. All these species showed prominent intimal protrusions of muscle into the pulmonary veins but no specific effect of high altitude in this respect.

  6. Wind study for high altitude platform design

    NASA Technical Reports Server (NTRS)

    Strganac, T. W.

    1979-01-01

    An analysis of upper air winds was performed to define the wind environment at potential operating altitudes for high altitude powered platform concepts. Wind conditions of the continental United States, Pacific area (Alaska to Sea of Japan), and European area (Norwegian and Mediterranean Sea) were obtained using a representative network of sites selected based upon adequate high altitude sampling, geographic dispersion, and observed upper wind patterns. A data base of twenty plus years of rawinsonde gathered wind information was used in the analysis. Annual variations from surface to 10 mb pressure altitude were investigated to encompass the practical operating range for the platform concepts. Parametric analysis for the United States and foreign areas was performed to provide a basis for vehicle system design tradeoffs. This analysis of wind magnitudes indicates the feasibility of annual operation at a majority of sites and more selective seasonal operation for the extreme conditions between the pressure altitudes of 100 to 25 mb based upon the assumed design speeds.

  7. Failure of polycythemia-induced increase in arterial oxygen content to suppress the anorexic effect of simulated high altitude in the adult rat.

    PubMed

    Norese, María F; Lezón, Christian E; Alippi, Rosa M; Martínez, María P; Conti, María I; Bozzini, Carlos E

    2002-01-01

    The anorexic effect of exposure to high altitude may be related to the reduction in the arterial oxygen content (Ca(O2)) induced by hypoxemia and possibly the associated decreased convective oxygen transport (COT). This study was then performed to evaluate the effects of either transfusion-induced polycythemia or previous acclimation to hypobaria with endogenously induced polycythemia on the anorexic effect of simulated high altitude (SHA) in adult female rats. Food consumption, expressed in g/d/100 g body weight, was reduced by 40% in rats exposed to 506 mbar for 4 d, as compared to control rats maintained in room air. Transfusion polycythemia, which significantly increased hematocrit, hemoglobin concentration, Ca(O2), and COT, did not change the anorexic response to the exposure to hypobaric air. Depression of food intake during exposure to SHA also occurred in rats fasted during 31 h before exposure and allowed to eat ad libitum for 2 h during exposure. Body mass loss was similar in 48-h fasted rats that were either hypoxic or normoxic. Body mass loss was similar in normoxic and hypoxic rats, the former eating the amount of food freely eaten by the latter. Hypoxia-acclimated rats with endogenously induced polycythemia taken to SHA again had diminished food intake and lost body mass at rates that were very close to those found in nonacclimated ones. Exposure to SHA also led to a decrease in food consumption, body weight, and plasma leptin in adult female mice. Analysis of data suggest that body mass loss that accompanies SHA-induced hypoxia is due to hypophagia and that experimental manipulation of the blood oxygen transport capacity cannot ameliorate it. Leptin does not appear to be an inducer of the anorexic response to hypoxia, at least in mice and rats.

  8. Exogenous sphingosine-1-phosphate boosts acclimatization in rats exposed to acute hypobaric hypoxia: assessment of haematological and metabolic effects.

    PubMed

    Chawla, Sonam; Rahar, Babita; Singh, Mrinalini; Bansal, Anju; Saraswat, Deepika; Saxena, Shweta

    2014-01-01

    The physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia. Efficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620 m for 6 hours) following S1P pre-treatment for three days. Altitude exposure of the control rats caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation) and respiratory alkalosis due to suboptimal renal compensation indicated by an overt alkaline pH of the mixed venous blood. This was associated with pronounced energy deficit in the hepatic tissue along with systemic oxidative stress and inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of hypoxia inducible factor-1α mediated erythropoiesis and renal S1P receptor 1 mediated haemoconcentation. The improved partial pressure of oxygen in the blood could further restore aerobic respiration and increase ATP content in the hepatic tissue of S1P treated animals. S1P could also protect the animals from hypoxia mediated oxidative stress and inflammation. The study findings highlight S1P's merits as a preconditioning agent for improving acclimatization to acute hypobaric hypoxia exposure. The results may have long term clinical application for improving physiological acclimatization of subjects venturing into high altitude for occupational or recreational purposes.

  9. Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

    PubMed Central

    Chawla, Sonam; Rahar, Babita; Singh, Mrinalini; Bansal, Anju; Saraswat, Deepika; Saxena, Shweta

    2014-01-01

    Background The physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia. Experimental Approach Efficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620m for 6 hours) following S1P pre-treatment for three days. Major Findings Altitude exposure of the control rats caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation) and respiratory alkalosis due to suboptimal renal compensation indicated by an overt alkaline pH of the mixed venous blood. This was associated with pronounced energy deficit in the hepatic tissue along with systemic oxidative stress and inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of hypoxia inducible factor-1α mediated erythropoiesis and renal S1P receptor 1 mediated haemoconcentation. The improved partial pressure of oxygen in the blood could further restore aerobic respiration and increase ATP content in the hepatic tissue of S1P treated animals. S1P could also protect the animals from hypoxia mediated oxidative stress and inflammation. Conclusion The study findings highlight S1P’s merits as a preconditioning agent for improving acclimatization to acute hypobaric hypoxia exposure. The results may have long term clinical application for improving physiological acclimatization of subjects venturing into high altitude for occupational or recreational purposes. PMID:24887065

  10. Neurologic decompression sickness following cabin pressure fluctuations at high altitude.

    PubMed

    Auten, Jonathan D; Kuhne, Michael A; Walker, Harlan M; Porter, Henry O

    2010-04-01

    Decompression sickness (DCS) occurs in diving, altitude chamber exposures, and unpressurized or depressurized high-altitude flights. Because DCS takes many forms, in-flight cases may be misinterpreted as hypoxia, hyperventilation, or viral illness, with resulting failure to respond appropriately. In this case, a 28-yr-old male pilot of a single-seat, tactical aircraft experienced 12 rapid pressure fluctuations while flying at 43,000 ft above sea level. He had no symptoms and decided to complete the flight, which required an additional 2 h in the air. Approximately 1 h later he began to experience fatigue, lightheadedness, and confusion, which he interpreted as onset of a viral illness. However, symptoms progressed to visual, cognitive, motor, and sensory degradations and it was with some difficulty that he landed safely at his destination. Neurologic DCS was suspected on initial evaluation by flight line medical personnel because of the delayed onset and symptom progression. He was transferred to a local Emergency Department and noted to have altered mental status, asymmetric motor deficits, and non-dermatomal paresthesias of the upper and lower extremities. Approximately 3.5 h after the incident and 2.5 h after the onset of symptoms he began hyperbaric oxygen therapy. He received partial relief at 30 min of the Navy DiveTable 6 and full resolution at 90 min; there were no recurrent symptoms at a 1-yr follow-up. This case highlights the importance of early recognition of in-flight DCS symptoms and landing as soon as possible rather than as soon as practical in all likely scenarios.

  11. 40 CFR 600.310-86 - Labeling of high altitude vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Labeling of high altitude vehicles... Regulations for 1977 and Later Model Year Automobiles-Labeling § 600.310-86 Labeling of high altitude vehicles... altitude vehicles according to § 600.306. (b) A high altitude vehicle may be labeled with a general or...

  12. 40 CFR 600.310-86 - Labeling of high altitude vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Labeling of high altitude vehicles... Regulations for 1977 and Later Model Year Automobiles-Labeling § 600.310-86 Labeling of high altitude vehicles... altitude vehicles according to § 600.306. (b) A high altitude vehicle may be labeled with a general or...

  13. Human immune circadian system in prolonged mild hypoxia during simulated flights.

    PubMed

    Coste, Olivier; Van Beers, Pascal; Bogdan, André; Touitou, Yvan

    2007-01-01

    An impairment of immunity is reported after long-haul flights, and the mild hypobaric hypoxia caused by pressurization in the passenger airline cabin may contribute to it. In this controlled crossover study, the effects of two levels of hypoxia, equivalent to 8000 and 12,000 feet above sea level, on the rhythm of CD3, CD4, and CD8 lymphocytes and plasma concentrations of the immunoglobulins A, G, and M were assessed. Fourteen healthy male volunteers, aged 23 to 39 years, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), simulating an altitude condition at 8,000 feet. This was followed by an additional 8.5 h study four weeks later simulating altitude conditions at 12,000 feet. The variables were assayed every 2 h over two 24 h cycles (control and hypoxic-exposure cycles). No significant effect of hypoxia on the studied circadian immune profiles were found. Therefore, the authors conclude that mild hypobaric hypoxia does not seem to be responsible for any quantitative changes during long-haul flights in the immune assays commonly used in routine clinical medicine practice.

  14. Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development.

    PubMed

    Hill, Catherine Mary; Baya, Ana; Gavlak, Johanna; Carroll, Annette; Heathcote, Kate; Dimitriou, Dagmara; L'Esperance, Veline; Webster, Rebecca; Holloway, John; Virues-Ortega, Javier; Kirkham, Fenella Jane; Bucks, Romola Starr; Hogan, Alexandra Marie

    2016-05-01

    Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory 'burden' of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our observations. © 2016 Associated Professional Sleep Societies

  15. [Method of studying the effects of pharmacological substances on work capacity of animals in hypobaric hypoxia].

    PubMed

    Spasov, A A; Kovalev, G V; Tsibanev, A V

    1990-08-01

    The method of the study of medical agent influence and biological active substances on duration of small laboratory animals swimming has been worked out excluding the air. For this purpose the animals were placed into altitude chamber, filled with water by 1/3 (one-third) of its volume being in antiorthostatic position on dipping into water. It has been established that at the altitude of 4000 (four thousand) meters high the rat swimming duration became shorter in comparison with their work under normal pressure in 2.5-4 times. Bemitil stimulating work in hypobaric hypoxia depresses it sharply. Bemitil stimulating influence on the rat efficiency did not appear with rising. Antioxidant substance ionol increased efficiency in normal conditions and in hypoxia AKS-85 adaptogenic compound increased swimming in the height duration to a greater degree, mildronat substance for efficiency restoration produced actoprotective influence.

  16. Accuracy of Handheld Blood Glucose Meters at High Altitude

    PubMed Central

    de Vries, Suzanna T.; Fokkert, Marion J.; Dikkeschei, Bert D.; Rienks, Rienk; Bilo, Karin M.; Bilo, Henk J. G.

    2010-01-01

    Background Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs. Methodology/Principal Findings Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude. Conclusion At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy. PMID:21103399

  17. Flight Performance During Exposure to Acute Hypobaric Hypoxia.

    PubMed

    Steinman, Yuval; van den Oord, Marieke H A H; Frings-Dresen, Monique H W; Sluiter, Judith K

    2017-08-01

    The purpose of the present study was to examine the influence of hypobaric hypoxia (HH) on a pilot's flight performance during exposure to simulated altitudes of 91, 3048, and 4572 m (300, 10,000, and 15,000 ft) and to monitor the pilot's physiological reactions. In a single-blinded counter-balanced design, 12 male pilots were exposed to HH while flying in a flight simulator that had been placed in a hypobaric chamber. Flight performance of the pilots, pilot's alertness level, Spo2, heart rate (HR), minute ventilation (VE), and breathing frequency (BF) were measured. A significant difference was found in Flight Profile Accuracy (FPA) between the three altitudes. Post hoc analysis showed no significant difference in performance between 91 m and 3048 m. A trend was observed at 4572 m, suggesting a decrease in flight performance at that altitude. Significantly lower alertness levels were observed at the start of the flight at 4572 m compared to 91 m, and at the end of the flight at 4572 m compared to the start at that altitude. Spo2 and BF decreased, and HR increased significantly with altitude. The present study did not provide decisive evidence for a decrease in flight performance during exposure to simulated altitudes of 3048 and 4572 m. However, large interindividual variation in pilots' flight performance combined with a gradual decrease in alertness levels observed in the present study puts into question the ability of pilots to safely fly an aircraft while exposed to these altitudes without supplemental oxygen.Steinman Y, van den Oord MHAH, Frings-Dresen MHW, Sluiter JK. Flight performance during exposure to acute hypobaric hypoxia. Aerosp Med Hum Perform. 2017; 88(8):760-767.

  18. Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years.

    PubMed

    Fehren-Schmitz, Lars; Georges, Lea

    2016-03-21

    Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype--characterized by reduced susceptibility to hypoxic stress--enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500-560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs.

  19. Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years

    PubMed Central

    Fehren-Schmitz, Lars; Georges, Lea

    2016-01-01

    Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype –characterized by reduced susceptibility to hypoxic stress–enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500–560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs. PMID:26996763

  20. Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia.

    PubMed

    Hota, Sunil K; Barhwal, Kalpana; Ray, Koushik; Singh, Shashi B; Ilavazhagan, G

    2008-05-01

    Exposure to high altitude is known to cause impairment in cognitive functions in sojourners. The molecular events leading to this behavioral manifestation, however, still remain an enigma. The present study aims at exploring the nature of memory impairment occurring on chronic exposure to hypobaric hypoxia and the possible role of glutamate in mediating it. Increased ionotropic receptor stimulation by glutamate under hypobaric hypoxic conditions could lead to calcium mediated excitotoxic cell death resulting in impaired cognitive functions. Since glutamate is cleared from the synapse by the Glial Glutamate Transporter, upregulation of the transporter can be a good strategy in preventing excitotoxic cell death. Considering previous reports on upregulation of the expression of Glial Glutamate Transporter on ceftriaxone administration, the therapeutic potential of ceftriaxone in ameliorating hypobaric hypoxia induced memory impairment was investigated in male Sprague Dawley rats. Exposure to hypobaric hypoxia equivalent to an altitude of 7600 m for 14 days lead to oxidative stress, chromatin condensation and neuronal degeneration in the hippocampus. This was accompanied by delayed memory retrieval as evident from increased latency and pathlength in Morris Water Maze. Administration of ceftriaxone at a dose of 200 mg/kg for 7 days and 14 days during the exposure on the other hand improved the performance of rats in the water maze along with decreased oxidative stress and enhanced neuronal survival when compared to hypoxic group without drug administration. An increased expression of Glial Glutamate Transporter was also observed following drug administration indicating faster clearance of glutamate from the synapse. The present study not only brings to light the effect of longer duration of exposure to hypobaric hypoxia on the memory functions, but also indicates the pivotal role played by glutamate in mediating excitotoxic neuronal degeneration at high altitude. The

  1. Wind study for high altitude platform design

    NASA Technical Reports Server (NTRS)

    Strganac, T. W.

    1979-01-01

    An analysis of upper air winds was performed to define the wind environment at potential operating altitudes for high-altitude powered platform concepts. Expected wind conditions of the contiguous United States, Pacific area (Alaska to Sea of Japan), and European area (Norwegian and Mediterranean Seas) were obtained using a representative network of sites selected based upon adequate high-altitude sampling, geographic dispersion, and observed upper wind patterns. A data base of twenty plus years of rawinsonde gathered wind information was used in the analysis. Annual variations from surface to 10 mb (approximately 31 km) pressure altitude were investigated to encompass the practical operating range for the platform concepts. Parametric analysis for the United States and foreign areas was performed to provide a basis for vehicle system design tradeoffs. This analysis of wind magnitudes indicates the feasibility of annual operation at a majority of sites and more selective seasonal operation for the extreme conditions between the pressure altitudes of 100 to 25 mb based upon the assumed design speeds.

  2. Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle

    PubMed Central

    Tao, Xiaoxiao; Lin, Mike T.; Thorington, Glyne U.; Wilson, Sean M.; Longo, Lawrence D.

    2015-01-01

    Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K+ channel activity. We hypothesized that to maintain oxygenation during LTH, basilar arteries (BA) in the ovine adult and near-term fetus would show increased large-conductance Ca2+ activated potassium (BK) channel activity. We measured BK channel activity, expression, and cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, and confocal microscopy, respectively, in myocytes from normoxic control and LTH adult and near-term fetus BA. Electrophysiological data showed that BK channels in LTH myocytes exhibited 1) lowered Ca2+ set points, 2) left-shifted activation voltages, and 3) longer dwell times. BK channels in LTH myocytes also appeared to be more dephosphorylated. These differences collectively make LTH BK channels more sensitive to activation. Studies using flow cytometry showed that the LTH fetus exhibited increased BK β1 subunit surface expression. In addition, in both fetal groups confocal microscopy revealed increased BK channel clustering and colocalization to myocyte lipid rafts. We conclude that increased BK channel activity in LTH BA occurred in association with increased channel affinity for Ca2+ and left-shifted voltage activation. Increased cerebrovascular BK channel activity may be a mechanism by which LTH adult and near-term fetal sheep can acclimatize to long-term high altitude hypoxia. Our findings suggest that increasing BK channel activity in cerebral myocytes may be a therapeutic target to ameliorate the adverse effects of high altitude in adults or of intrauterine hypoxia in the fetus. PMID:25599571

  3. Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude.

    PubMed

    Martin, Daniel S; Gilbert-Kawai, Edward T; Meale, Paula M; Fernandez, Bernadette O; Cobb, Alexandra; Khosravi, Maryam; Mitchell, Kay; Grocott, Michael P W; Levett, Denny Z H; Mythen, Michael G; Feelisch, Martin

    2013-11-01

    The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients. © 2013. Published by Elsevier Inc. All rights reserved.

  4. Human red blood cell aging at 5,050-m altitude: a role during adaptation to hypoxia.

    PubMed

    Samaja, M; Brenna, L; Allibardi, S; Cerretelli, P

    1993-10-01

    To test the hypothesis that the human red blood cell aging process participates actively in the adaptation to hypoxia, we studied some physical and biochemical hematologic variables in 10 volunteers at sea level (SL) and after 1 (1WK) or 5 wk (5WK) of exposure to 5,050-m altitude. The 2,3-diphosphoglycerate-to-hemoglobin ratio (2,3-DPG/Hb) was 0.88 +/- 0.03 (mol/mol) at SL and increased to 1.08 +/- 0.03 (P = 0.002) and 1.28 +/- 0.05 (P < 0.0001) at 1WK and 5WK, respectively. The average red blood cell density (D50), which is inversely proportional to the fraction of young red blood cells and is therefore an index of the red blood cell aging process, was 1.1053 +/- 0.0007 g/ml at SL and decreased to 1.1046 +/- 0.0008 g/ml (NS) and 1.1018 +/- 0.0008 g/ml (P < 0.001) at 1WK and 5WK, respectively. D50 was correlated with 2,3-DPG/Hb at SL (P = 0.004), only weakly at 5WK (P = 0.1), but not at all at 1WK. The arterial O2 saturation was correlated with the change of 2,3-DPG/Hb in 1WK (P = 0.02) and that of D50 in 5WK (P = 0.04). It is concluded that short-term (1WK) increase of 2,3-DPG/Hb is not associated with the erythropoietic response but is presumably due to respiratory alkalosis. By contrast, after prolonged hypoxia (5WK), erythropoiesis may provide an efficient way for increasing blood 2,3-DPG through an augmented proportion of young red blood cells.

  5. Effects of High Terrestrial Altitude on Military Performance

    DTIC Science & Technology

    1989-04-18

    ments were observed. In a second study at the same altitude neither age nor altitude changed urinary 17- ketogenic steroid excretion rates or Fatigue...due to decreased food intake) and up to 5 liters of water per day may be required. A balanced diet at high altitude is 52% car- bohydrates, 33% fats

  6. Bench Evaluation of Four Portable Oxygen Concentrators Under Different Conditions Representing Altitudes of 2438, 4200, and 8000 m.

    PubMed

    Bunel, Vincent; Shoukri, Amr; Choin, Frederic; Roblin, Serge; Smith, Cindy; Similowski, Thomas; Morélot-Panzini, Capucine; Gonzalez, Jesus

    2016-12-01

    Bunel, Vincent, Amr Shoukri, Frederic Choin, Serge Roblin, Cindy Smith, Thomas Similowski, Capucine Morélot-Panzini, and Jésus Gonzalez. Bench evaluation of four portable oxygen concentrators under different conditions representing altitudes of 2438, 4200, and 8000 m. High Alt Med Biol. 17:370-374, 2016.-Air travel is responsible for a reduction of the partial pressure of oxygen (O 2 ) as a result of the decreased barometric pressure. This hypobaric hypoxia can be dangerous for passengers with respiratory diseases, requiring initiation or intensification of oxygen therapy during the flight. In-flight oxygen therapy can be provided by portable oxygen concentrators, which are less expensive and more practical than oxygen cylinders, but no study has evaluated their capacity to concentrate oxygen under simulated flight conditions. We tested four portable oxygen concentrators during a bench test study. The O 2 concentrations (FO 2 ) produced were measured under three different conditions: in room air at sea level, under hypoxia due to a reduction of the partial pressure of O 2 (normobaric hypoxia, which can be performed routinely), and under hypoxia due to a reduction of atmospheric pressure (hypobaric hypoxia, using a chamber manufactured by Airbus Defence and Space). The FO 2 obtained under conditions of hypobaric hypoxia (chamber) was lower than that measured in room air (0.92 [0.89-0.92] vs. 0.93 [0.92-0.94], p = 0.029), but only one portable oxygen concentrator was unable to maintain an FO 2 ≥ 0.90 (0.89 [0.89-0.89]). In contrast, under conditions of normobaric hypoxia (tent) simulating an altitude of 2438 m, none of the apparatuses tested was able to achieve an FO 2 greater than 0.76. (0.75 [0.75-0.76] vs. 0.93 [0.92-0.94], p = 0.029). Almost all portable oxygen concentrators were able to generate a sufficient quantity of O 2 at simulated altitudes of 2438 m and can therefore be used in the aircraft cabin. Unfortunately, verification of the

  7. Hypoxia and Coriolis Illusion in Pilots During Simulated Flight.

    PubMed

    Kowalczuk, Krzysztof P; Gazdzinski, Stefan P; Janewicz, Michał; Gąsik, Marek; Lewkowicz, Rafał; Wyleżoł, Mariusz

    2016-02-01

    Pilots' vision and flight performance may be impeded by spatial disorientation and high altitude hypoxia. The Coriolis illusion affects both orientation and vision. However, the combined effect of simultaneous Coriolis illusion and hypoxia on saccadic eye movement has not been evaluated. A simulated flight was performed by 14 experienced pilots under 3 conditions: once under normal oxygen partial pressure and twice under reduced oxygen partial pressures, reflecting conditions at 5000 m and 6000 m (16,404 and 19,685 ft), respectively. Eye movements were evaluated with a saccadometer. At normal oxygen pressure, Coriolis illusion resulted in 55% and 31% increases in mean saccade amplitude and duration, respectively, but a 32% increase in mean saccade frequency was only noted for saccades smaller than the angular distance between cockpit instruments, suggesting an increase in the number of correction saccades. At lower oxygen pressures a pronounced increase in the standard deviation of all measures was noticed; however, the pattern of changes remained unchanged. Simple measures of saccadic movement are not affected by short-term hypoxia, most likely due to compensatory mechanisms.

  8. Does Swimming at a Moderate Altitude Favor a Lower Oxidative Stress in an Intensity-Dependent Manner? Role of Nonenzymatic Antioxidants.

    PubMed

    Casuso, Rafael A; Aragón-Vela, Jerónimo; López-Contreras, Gracia; Gomes, Silvana N; Casals, Cristina; Barranco-Ruiz, Yaira; Mercadé, Jordi J; Huertas, Jesus R

    2017-03-01

    Casuso, Rafael A., Jerónimo Aragón-Vela, Gracia López-Contreras, Silvana N. Gomes, Cristina Casals, Yaira Barranco-Ruiz, Jordi J. Mercadé, and Jesus R. Huertas. Does swimming at a moderate altitude favor a lower oxidative stress in an intensity-dependent manner? Role of nonenzymatic antioxidants. High-Alt Med Biol. 18:46-55, 2017.-we aimed to describe oxidative damage and enzymatic and nonenzymatic antioxidant responses to swimming at different intensities in hypoxia. We recruited 12 highly experienced swimmers who have been involved in competitive swimming for at least 9 years. They performed a total of six swimming sessions carried out at low (LOW), moderate (MOD), or high (HIGH) intensity at low altitude (630 m) and at 2320 m above sea level. Blood samples were collected before the session (Pre), after the cool down (Post), and after 15 minutes of recovery (Rec). Blood lactate (BL) and heart rate were recorded throughout the main part of the session. Average velocities did not change between hypoxia and normoxia. We found a higher BL in response to MOD intensity in hypoxia. Plasmatic hydroperoxide level decreased at all intensities when swimming in hypoxia. This effect coincided with a lower glutation peroxidase activity and a marked mobilization of the circulating levels of α-tocopherol and coenzyme Q10 in an intensity-dependent manner. Our results suggest that, regardless of the intensity, no oxidative damage is found in response to hypoxic swimming in well-trained swimmers. Indeed, swimmers show a highly efficient antioxidant system by stimulating the mobilization of nonenzymatic antioxidants.

  9. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Amann, Markus

    2015-01-01

    Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

  10. Hypoxia symptoms reported during helicopter operations below 10,000 ft: a retrospective survey.

    PubMed

    Smith, Adrian

    2005-08-01

    During routine aviation medicine training, rotary-wing aircrew are instructed that the impact of hypoxia on them from flying in unpressurized cabins up to 10,000 ft (3048 m) above mean sea level (AMSL) is relatively small and has few implications for aviation safety. Such reassurance is based on data derived from experiments conducted on resting subjects and may not reflect the true impact of hypoxia in aircrew engaged in operational tasks. A survey listing common symptoms of hypoxia was distributed to Australian Army helicopter aircrew who had operated at altitudes up to 10,000 ft AMSL. There were 53 surveys that were returned (71% response), representing 25 loadmasters, 23 pilots, and 5 aircrewman technicians. All respondents were Australian Army aircrew. One or more symptoms consistent with hypoxia were reported by 86.6% of non-pilot aircrew and 60.9% of pilots. 60% of non-pilot aircrew reported four or more symptoms, compared with only 17% of pilots. The most commonly reported symptoms were difficulty with calculations (45%), feeling light-headed (38%), delayed reaction time (38%), and mental confusion (36%). Loadmasters reported more symptoms (mean 5.4) than pilots (mean 2.2) (p < 0.001). From the narratives provided (n = 21), aircrew experienced potentially operationally significant symptoms at a mean altitude of 8462 ft (2579 m). The helicopter aircrew surveyed reported symptoms consistent with hypoxia at altitudes within the so-called physiological zone; loadmasters reported more effects than pilots. It may be inappropriate to emphasize the benign nature of the physiological zone during aviation medicine training of a non-resting population such as helicopter aircrew.

  11. High‐altitude ancestry protects against hypoxia‐associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Vargas, Enrique; Armaza, J Fernando; Wilson, Megan J; Niermeyer, Susan; Moore, Lorna G

    2007-01-01

    Objective The chronic hypoxia of high‐altitude (⩾2500 m) residence has been shown to decrease birth weight in all populations studied to date. However, multigenerational high‐altitude populations appear protected relative to newcomer groups. This study aimed to determine whether such protection exists independently of other factors known to influence fetal growth and whether admixed populations (ie, people having both high‐ and low‐altitude ancestry) show an intermediate level of protection. Design 3551 medical records from consecutive deliveries to Andean, European or Mestizo (ie, admixed) women at low, intermediate or high altitudes in Bolivia were evaluated for maternal characteristics influencing fetal growth as measured by birth weight and the frequency of small for gestational age births (SGA or ⩽10th percentile birth weight for gestational age and sex). Two‐way analysis of variance and χ2 tests were used to compare maternal and infant characteristics. The effects of ancestry or altitude on SGA and birth weight were assessed using logistic or linear regression models, respectively. Results Altitude decreased birth weight and increased SGA in all ancestry groups. Andean infants weighed more and were less often SGA than Mestizo or European infants at high altitude (13%, 16% and 33% respectively, p<0.01). After accounting for the influences of maternal hypertensive complications of pregnancy, parity, body weight, and number of prenatal visits, European relative to Andean ancestry increased the frequency of SGA at high altitude nearly fivefold. Conclusions Andean relative to European ancestry protects against altitude‐associated reductions in fetal growth. The intermediate protection seen in the admixed (Mestizo) group is consistent with the influence of genetic or other Andean‐specific protective characteristics. PMID:17329275

  12. Cerebrovascular reactivity is increased with acclimatization to 3,454 m altitude.

    PubMed

    Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten

    2015-08-01

    Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAv mean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26 ± 4 years (mean ± s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAv mean was not altered. Hypercapnic CVR was decreased at HA0 (1.16% ± 0.16%/mm Hg, mean ± s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13% ± 0.18% and 2.96% ± 0.10%/mm Hg) and HA22 (3.32% ± 0.12% and 3.24% ± 0.14%/mm Hg) compared with SL (1.98% ± 0.22% and 2.38% ± 0.10%/mm Hg; P < 0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAv mean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude.

  13. How do you approach seizures in the high altitude traveler?

    PubMed

    Maa, Edward H

    2011-01-01

    Counseling patients who suffer first-time or break- through seizures can be difficult, particularly when controllable external factors may be contributing to the lowering of their seizure threshold. High altitude as a potential trigger for seizures is a common question in our epilepsy clinics in Colorado, and this article reviews the existing anecdotal literature, presents our local experience with high altitude seizures (HAS), offers possible mechanisms to explain how high altitude may trigger seizures, and suggests an initial work-up and prophylactic strategies for future high altitude exposures.

  14. The effect of α1 -adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.

    PubMed

    Tymko, Michael M; Tremblay, Joshua C; Hansen, Alex B; Howe, Connor A; Willie, Chris K; Stembridge, Mike; Green, Daniel J; Hoiland, Ryan L; Subedi, Prajan; Anholm, James D; Ainslie, Philip N

    2017-03-01

    ), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate-intensity exercise at sea level was abolished via α 1 -adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate-intensity exercise, and administration of α 1 -adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α 1 -adrenergic pathway and endothelial function. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  15. Hyperintense white matter lesions in 50 high-altitude pilots with neurologic decompression sickness.

    PubMed

    McGuire, Stephen A; Sherman, Paul M; Brown, Anthony C; Robinson, Andrew Y; Tate, David F; Fox, Peter T; Kochunov, Peter V

    2012-12-01

    Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

  16. Hyperintense White Matter Lesions in 50 High-Altitude Pilots With Neurologic Decompression Sickness

    PubMed Central

    McGuire, Stephen A.; Sherman, Paul M.; Brown, Anthony C.; Robinson, Andrew Y.; Tate, David F.; Fox, Peter T.; Kochunov, Peter V.

    2013-01-01

    Introduction Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. Methods We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. Results The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. Conclusion A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions. PMID:23316539

  17. A variant of the endothelial nitric oxide synthase gene (NOS3) associated with AMS susceptibility is less common in the Quechua, a high altitude Native population.

    PubMed

    Wang, Pei; Ha, Alice Y N; Kidd, Kenneth K; Koehle, Michael S; Rupert, Jim L

    2010-01-01

    Endothelial nitric oxide synthase (eNOS) is a vascular enzyme that produces nitric oxide, a transient signaling molecule that by vasodilatation regulates blood flow and pressure. Nitric oxide is believed to play roles in both short-term acclimatization and long-term evolutionary adaptation to environmental hypoxia. Several laboratories, including ours, have shown that variants in NOS3 (the gene encoding eNOS) are overrepresented in individuals with altitude-related illnesses such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), suggesting that NOS3 genotypes contribute to altitude tolerance. To further test our hypothesis that the G allele at the G894T polymorphism in NOS3 (dbSNP number: rs1799983; protein polymorphism Glu298Asp) is beneficial in hypoxic environments, we compared frequencies of this allele in an altitude-adapted Amerindian population, Quechua of the Andean altiplano, with those in a lowland Amerindian population, Maya of the Yucatan Peninsula. While common in both populations, the G allele was significantly more frequent in the highlanders. Taken together, our data suggest that this variant in NOS3, which has been previously associated with higher levels of nitric oxide, contributes to both acclimatization and adaptation to altitude.

  18. Users guide to high altitude imagery of Michigan

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A guide to the high altitude imagery of Michigan outlines the areas of the state covered by selected recent high altitude aircraft and Earth Resources Technology Satellite flights. The types of remote sensing used are described. Maps of the flight coverage areas are included along with price lists of available imagery.

  19. Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development

    PubMed Central

    Hill, Catherine Mary; Baya, Ana; Gavlak, Johanna; Carroll, Annette; Heathcote, Kate; Dimitriou, Dagmara; L'Esperance, Veline; Webster, Rebecca; Holloway, John; Virues-Ortega, Javier; Kirkham, Fenella Jane; Bucks, Romola Starr; Hogan, Alexandra Marie

    2016-01-01

    Study Objectives: Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory ‘burden’ of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. Methods: This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. Results: Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. Conclusions: Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our

  20. High-altitude physiology: lessons from Tibet

    NASA Astrophysics Data System (ADS)

    Wagner, Peter D.; Simonson, Tatum S.; Wei, Guan; Wagner, Harrieth; Wuren, Tanna; Yan, Ma; Qin, Ga; Ge, Rili

    2013-05-01

    Polycythemia is a universal lowlander response to altitude; healthy Andean high-altitude natives also have elevated [Hb]. While this may enhance O2 transport to tissues, studies have shown that acute isovolumic changes in [Hb] do not affect exercise capacity. Many high-altitude Tibetans have evolved sea-level values of [Hb], providing a natural opportunity to study this issue. In 21 young healthy male Tibetans with [Hb] between 15 and 23 g/dl, we measured VO2MAX and O2 transport capacity at 4200m. VO2MAX was higher when [Hb] was lower (P<0.05), enabled by both higher cardiac output and muscle O2 diffusional conductance, but neither ventilation nor the alveolar-arterial PO2 difference (AaPO2) varied with [Hb]. In contrast, Andean high altitude natives remain polycythemic with larger lungs and higher lung diffusing capacity, a smaller exercising AaPO2, and lower ventilation. The challenges now are (1) to understand the different adaptive pathways used by Andeans and Tibetans, and (2) to determine in Tibetans whether, during evolution, reduced [Hb] appeared first, causing compensatory cardiac and muscle adaptations, or if enhanced cardiac function and muscle O2 transport capacity appeared first, permitting secondary reduction in [Hb]. For (2), further research is necessary to determine the basis of enhanced cardiac function and muscle O2 transport, and identify molecular targets of evolution in heart and muscle. Putative mutations can then be timed and compared to appearance of those affecting [Hb].

  1. Design and Development of a High Altitude Protective Assembly.

    DTIC Science & Technology

    CWU-3/P ANTIGRAVITY SUITS, CWU-12/P ANTIEXPOSURE SUITS, HAPA(HIGH ALTITUDE PROTECTIVE ASSEMBLIES), *HIGH ALTITUDE PROTECTIVE ASSEMBLIES, LPU-3/P LIFE PRESERVERS, MA-3 VENTILATION GARMENTS, PARACHUTE HARNESSES, PARTIAL PRESSURE SUITS.

  2. Enhancing team-sport athlete performance: is altitude training relevant?

    PubMed

    Billaut, François; Gore, Christopher J; Aughey, Robert J

    2012-09-01

    Field-based team sport matches are composed of short, high-intensity efforts, interspersed with intervals of rest or submaximal exercise, repeated over a period of 60-120 minutes. Matches may also be played at moderate altitude where the lower oxygen partial pressure exerts a detrimental effect on performance. To enhance run-based performance, team-sport athletes use varied training strategies focusing on different aspects of team-sport physiology, including aerobic, sprint, repeated-sprint and resistance training. Interestingly, 'altitude' training (i.e. living and/or training in O(2)-reduced environments) has only been empirically employed by athletes and coaches to improve the basic characteristics of speed and endurance necessary to excel in team sports. Hypoxia, as an additional stimulus to training, is typically used by endurance athletes to enhance performance at sea level and to prepare for competition at altitude. Several approaches have evolved in the last few decades, which are known to enhance aerobic power and, thus, endurance performance. Altitude training can also promote an increased anaerobic fitness, and may enhance sprint capacity. Therefore, altitude training may confer potentially-beneficial adaptations to team-sport athletes, which have been overlooked in contemporary sport physiology research. Here, we review the current knowledge on the established benefits of altitude training on physiological systems relevant to team-sport performance, and conclude that current evidence supports implementation of altitude training modalities to enhance match physical performances at both sea level and altitude. We hope that this will guide the practice of many athletes and stimulate future research to better refine training programmes.

  3. Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

    PubMed

    Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Latshang, Tsogyal D; Lo Cascio, Christian M; Sadler, Ross; Stadelmann, Katrin; Tesler, Noemi; Huber, Reto; Achermann, Peter; Bloch, Konrad E; Kohler, Malcolm

    2014-05-01

    Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/μl 95 % CI -370.8/-119.0, lactadherin+ -202/μl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/μl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 μl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

  4. Lung volumes, pulmonary ventilation, and hypoxia following rapid decompression to 60,000 ft (18,288 m).

    PubMed

    Connolly, Desmond M; D'Oyly, Timothy J; McGown, Amanda S; Lee, Vivienne M

    2013-06-01

    Rapid decompressions (RD) to 60,000 ft (18,288 m) were undertaken by six subjects to provide evidence of satisfactory performance of a contemporary, partial pressure assembly life support system for the purposes of flight clearance. A total of 12 3-s RDs were conducted with subjects breathing 56% oxygen (balance nitrogen) at the base (simulated cabin) altitude of 22,500 ft (6858 m), switching to 100% oxygen under 72 mmHg (9.6 kPa) of positive pressure at the final (simulated aircraft) altitude. Respiratory pressures, flows, and gas compositions were monitored continuously throughout. All RDs were completed safely, but one subject experienced significant hypoxia during the minute at final altitude, associated with severe hemoglobin desaturation to a low of 53%. Accurate data on subjects' lung volumes were obtained and individual responses post-RD were reviewed in relation to patterns of pulmonary ventilation. The occurrence of severe hypoxia is explained by hypoventilation in conjunction with unusually large lung volumes (total lung capacity 10.18 L). Subjects' lung volumes and patterns of pulmonary ventilation are critical, but idiosyncratic, determinants of alveolar oxygenation and severity of hypoxia following RD to 60,000 ft (18,288 m). At such extreme altitudes even vaporization of water condensate in the oxygen mask may compromise oxygen delivery. An altitude ceiling of 60,000 ft (18,288 m) is the likely threshold for reliable protection using partial pressure assemblies and aircrew should be instructed to take two deep 'clearing' breaths immediately following RD at such extreme pressure breathing altitudes.

  5. Nitric oxide in red blood cell adaptation to hypoxia.

    PubMed

    Zhao, Yajin; Wang, Xiang; Noviana, Milody; Hou, Man

    2018-06-01

    Nitric oxide (NO) appears to be involved in virtually every aspect of cardiovascular biology. Most attention has been focused on the role of endothelial-derived NO in basal blood flow regulation by relaxing vascular smooth muscle; however, it is now known that NO derived from red blood cells (RBCs) plays a fundamental role in vascular homeostasis by enhancing oxygen (O2) release at the cellular and physiological level. Hypoxia is an often seen problem in diverse conditions; systemic adaptations to hypoxia permit people to adjust to the hypoxic environment at high altitudes and to disease processes. In addition to the cardiopulmonary and hematologic adaptations that support systemic O2 delivery in hypoxia, RBCs assist through newly described NO-based mechanisms, in line with their vital role in O2 transport and delivery. Furthermore, to increase the local blood flow in proportion to metabolic demand, NO regulates membrane mechanical properties thereby modulating RBC deformability and O2 carrying-releasing function. In this review article, we focus on the effect of NO bioactivity on RBC-based mechanisms that regulate blood flow and RBC deformability. RBC adaptations to hypoxia are summarized, with particular attention to NO-dependent S-nitrosylation of membrane proteins and hemoglobin (S-nitrosohemoglobin). The NO/S-nitrosylation/RBC vasoregulatory cascade contributes fundamentally to the molecular understanding of the role of NO in human adaptation to hypoxia and may inform novel therapeutic strategies.

  6. Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia

    NASA Technical Reports Server (NTRS)

    Loeppky, J. A.; Roach, R. C.; Selland, M. A.; Scotto, P.; Greene, E. R.; Luft, U. C.

    1993-01-01

    To determine the effects of hypoxia on physiological responses to simulated zero-gravity cardiopulmonary and fluid balance measurements were made in 6 subjects before and during 5-degree head-down bed rest (HDBR) over 8 d at 10,678 ft and a second time at this altitude as controls (CON). The V-dot(O2)(max) increased by 9 percent after CON, but fell 3 percent after HDBR. This reduction in work capacity during HDBR could be accounted for by inactivity. The heart rate response to a head-up tilt was greatly enhanced following HDBR, while mean blood pressure was lower. No significant negative impact of HDBR was noted on the ability to acclimatize to hypoxia in terms of pulmonary mechanics, gas exchange, circulatory or mental function measurements. No evidence of pulmonary interstitial edema or congestion was noted during HDBR at the lower PIO2 and blood rheology properties were not negatively altered. Symptoms of altitude illness were more prevalent, but not marked, during HDBR and arterial blood gases and oxygenation were not seriously effected by simulated microgravity. Declines in base excess with altitude were similar in both conditions. The study demonstrated a minimal effect of HDBR on the ability to adjust to this level of hypoxia.

  7. Mitochondrial function at extreme high altitude.

    PubMed

    Murray, Andrew J; Horscroft, James A

    2016-03-01

    At high altitude, barometric pressure falls and with it inspired P(O2), potentially compromising O2 delivery to the tissues. With sufficient acclimatisation, the erythropoietic response increases red cell mass such that arterial O2 content (C(aO2)) is restored; however arterial P(O2)(P(aO2)) remains low, and the diffusion of O2 from capillary to mitochondrion is impaired. Mitochondrial respiration and aerobic capacity are thus limited, whilst reactive oxygen species (ROS) production increases. Restoration of P(aO2) with supplementary O2 does not fully restore aerobic capacity in acclimatised individuals, possibly indicating a peripheral impairment. With prolonged exposure to extreme high altitude (>5500 m), muscle mitochondrial volume density falls, with a particular loss of the subsarcolemmal population. It is not clear whether this represents acclimatisation or deterioration, but it does appear to be regulated, with levels of the mitochondrial biogenesis factor PGC-1α falling, and shows similarities to adapted Tibetan highlanders. Qualitative changes in mitochondrial function also occur, and do so at more moderate high altitudes with shorter periods of exposure. Electron transport chain complexes are downregulated, possibly mitigating the increase in ROS production. Fatty acid oxidation capacity is decreased and there may be improvements in biochemical coupling at the mitochondrial inner membrane that enhance O2 efficiency. Creatine kinase expression falls, possibly impairing high-energy phosphate transfer from the mitochondria to myofibrils. In climbers returning from the summit of Everest, cardiac energetic reserve (phosphocreatine/ATP) falls, but skeletal muscle energetics are well preserved, possibly supporting the notion that mitochondrial remodelling is a core feature of acclimatisation to extreme high altitude. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  8. Interaction between marihuana and altitude on a complex behavioral task in baboons.

    DOT National Transportation Integrated Search

    1975-01-01

    Marihuana, or its principal active ingredient, delta-9-tetrahydrocannabinol (delta9-THC), impairs performance on complex behavioral tasks in animals and man. Although there exists some evidence that altitude-induced hypoxia potentiates the physiologi...

  9. Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Stone, H. L.

    1972-01-01

    Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

  10. Cerebrovascular reactivity is increased with acclimatization to 3,454 m altitude

    PubMed Central

    Flück, Daniela; Siebenmann, Christoph; Keiser, Stefanie; Cathomen, Adrian; Lundby, Carsten

    2015-01-01

    Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAvmean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26±4 years (mean±s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAvmean was not altered. Hypercapnic CVR was decreased at HA0 (1.16%±0.16%/mm Hg, mean±s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13%±0.18% and 2.96%±0.10%/mm Hg) and HA22 (3.32%±0.12% and 3.24%±0.14%/mm Hg) compared with SL (1.98%±0.22% and 2.38%±0.10%/mm Hg; P<0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAvmean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude. PMID:25806704

  11. Acute physical exercise under hypoxia improves sleep, mood and reaction time.

    PubMed

    de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

    2016-02-01

    This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time.

  12. The effect of α1‐adrenergic blockade on post‐exercise brachial artery flow‐mediated dilatation at sea level and high altitude

    PubMed Central

    Tremblay, Joshua C.; Hansen, Alex B.; Howe, Connor A.; Willie, Chris K.; Stembridge, Mike; Green, Daniel J.; Hoiland, Ryan L.; Subedi, Prajan; Anholm, James D.; Ainslie, Philip N.

    2016-01-01

    m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow‐mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate‐intensity exercise at sea level was abolished via α1‐adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate‐intensity exercise, and administration of α1‐adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α1‐adrenergic pathway and endothelial function. PMID:28032333

  13. Effects of high altitude and exercise on marksmanship.

    PubMed

    Tharion, W J; Hoyt, R W; Marlowe, B E; Cymerman, A

    1992-02-01

    The effects of exercise and high altitude (3,700 m to 4,300 m) on marksmanship accuracy and sighting time were quantified in 16 experienced marksmen. Subjects dry-fired a disabled rifle equipped with a laser-based system from a free-standing position. The 2.3-cm circular target was at a distance of 5 m. Marksmanship was assessed under the following conditions: 1) at rest at sea level; 2) immediately after a 21-km run/walk ascent from 1,800 m to 4,300 m elevation; 3) at rest during days 1 to 3 at altitude; 4) at rest during days 14 to 16 at altitude; and 5) immediately after a second ascent after 17 d at altitude. Exercise reduced marksmanship accuracy (p less than 0.05) but did not affect sighting time. Acute altitude exposure reduced marksmanship accuracy, and decreased sighting time (p less than 0.05). However, after residence at altitude, accuracy and sighting time at rest returned to sea level values. Exercise and acute altitude exposure had similar but independent detrimental effects on marksmanship.

  14. Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

    PubMed

    Wang, Kang; Smith, Zachary M; Buxton, Richard B; Swenson, Erik R; Dubowitz, David J

    2015-12-15

    Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia. Copyright © 2015 the American

  15. Effects of Carbohydrate and Glutamine Supplementation on Oral Mucosa Immunity after Strenuous Exercise at High Altitude: A Double-Blind Randomized Trial.

    PubMed

    Caris, Aline Venticinque; Da Silva, Edgar Tavares; Dos Santos, Samile Amorim; Tufik, Sergio; Dos Santos, Ronaldo Vagner Thomatieli

    2017-07-03

    This study analyzed the effects of carbohydrate and glutamine supplementation on salivary immunity after exercise at a simulated altitude of 4500 m. Fifteen volunteers performed exercise of 70% of VO 2peak until exhaustion and were divided into three groups: hypoxia placebo, hypoxia 8% maltodextrin (200 mL/20 min), and hypoxia after six days glutamine (20 g/day) and 8% maltodextrin (200 mL/20 min). All procedures were randomized and double-blind. Saliva was collected at rest (basal), before exercise (pre-exercise), immediately after exercise (post-exercise), and two hours after exercise. Analysis of Variance (ANOVA) for repeated measures and Tukey post hoc test were performed. Statistical significance was set at p < 0.05. SaO₂% reduced when comparing baseline vs. pre-exercise, post-exercise, and after recovery for all three groups. There was also a reduction of SaO₂% in pre-exercise vs. post-exercise for the hypoxia group and an increase was observed in pre-exercise vs. recovery for both supplementation groups, and between post-exercise and for the three groups studied. There was an increase of salivary flow in post-exercise vs. recovery in Hypoxia + Carbohydrate group. Immunoglobulin A (IgA) decreased from baseline vs. post-exercise for Hypoxia + Glutamine group. Interleukin 10 (IL-10) increased from post-exercise vs. after recovery in Hypoxia + Carbohydrate group. Reduction of tumor necrosis factor alpha (TNF-α) was observed from baseline vs. post-exercise and after recovery for the Hypoxia + Carbohydrate group; a lower concentration was observed in pre-exercise vs. post-exercise and recovery. TNF-α had a reduction from baseline vs. post-exercise for both supplementation groups, and a lower secretion between baseline vs. recovery, and pre-exercise vs. post-exercise for Hypoxia + Carbohydrate group. Five hours of hypoxia and exercise did not change IgA. Carbohydrates, with greater efficiency than glutamine, induced anti-inflammatory responses.

  16. Convergent Evolution of Rumen Microbiomes in High-Altitude Mammals.

    PubMed

    Zhang, Zhigang; Xu, Dongming; Wang, Li; Hao, Junjun; Wang, Jinfeng; Zhou, Xin; Wang, Weiwei; Qiu, Qiang; Huang, Xiaodan; Zhou, Jianwei; Long, Ruijun; Zhao, Fangqing; Shi, Peng

    2016-07-25

    Studies of genetic adaptation, a central focus of evolutionary biology, most often focus on the host's genome and only rarely on its co-evolved microbiome. The Qinghai-Tibetan Plateau (QTP) offers one of the most extreme environments for the survival of human and other mammalian species. Yaks (Bos grunniens) and Tibetan sheep (T-sheep) (Ovis aries) have adaptations for living in this harsh high-altitude environment, where nomadic Tibetan people keep them primarily for food and livelihood [1]. Adaptive evolution affects energy-metabolism-related genes in a way that helps these ruminants live at high altitude [2, 3]. Herein, we report convergent evolution of rumen microbiomes for energy harvesting persistence in two typical high-altitude ruminants, yaks and T-sheep. Both ruminants yield significantly lower levels of methane and higher yields of volatile fatty acids (VFAs) than their low-altitude relatives, cattle (Bos taurus) and ordinary sheep (Ovis aries). Ultra-deep metagenomic sequencing reveals significant enrichment in VFA-yielding pathways of rumen microbial genes in high-altitude ruminants, whereas methanogenesis pathways show enrichment in the cattle metagenome. Analyses of RNA transcriptomes reveal significant upregulation in 36 genes associated with VFA transport and absorption in the ruminal epithelium of high-altitude ruminants. Our study provides novel insights into the contributions of microbiomes to adaptive evolution in mammals and sheds light on the biological control of greenhouse gas emissions from livestock enteric fermentation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Can people with Raynaud's phenomenon travel to high altitude?

    PubMed

    Luks, Andrew M; Grissom, Colin K; Jean, Dominique; Swenson, Erik R

    2009-01-01

    To determine whether high altitude travel adversely affects mountain enthusiasts with Raynaud's phenomenon. Volunteers with Raynaud's phenomenon were recruited using announcements disseminated by organizations dedicated to climbing or wilderness travel and Internet discussion boards dedicated to mountain activities to complete an online, anonymous survey. Survey questions addressed demographic variables, aspects of their Raynaud's phenomenon, and features of their mountain activities. Respondents compared experiences with Raynaud's phenomenon between high (>2440 m; 8000 feet) and low elevations and rated agreement with statements concerning their disease and the effects of high altitude. One hundred forty-two people, 98% of whom had primary Raynaud's phenomenon, completed the questionnaire. Respondents spent 5 to 7 days per month at elevations above 2440 m and engaged in 5.4 +/- 2.0 different activities. Eighty-nine percent of respondents engaged in winter sports and only 22% reported changing their mountain activities because of Raynaud's phenomenon. Respondents reported a variety of tactics to prevent and treat Raynaud's attacks, but only 12% used prophylactic medications. Fifteen percent of respondents reported an episode of frostbite following a Raynaud's phenomenon attack at high altitude. There was considerable heterogeneity in participants' perceptions of the frequency, duration, and severity of attacks at high altitude compared to their home elevation. Motivated individuals with primary Raynaud's phenomenon, employing various prevention and treatment strategies, can engage in different activities, including winter sports, at altitudes above 2440 m. Frostbite may be common in this population at high altitude, and care must be taken to prevent its occurrence.

  18. High Altitude Plasma Instrument (HAPI) data analysis

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1994-01-01

    The objectives of the Dynamics Explorer mission are to investigate the coupling of energy, mass, and momentum among the earth's magnetosphere, ionosphere, and upper atmosphere. At launch, on August 3, 1981, DE-1 was placed into an elliptical polar orbit having an apogee of 23,130 km to allow global auroral imaging and crossings of auroral field lines at altitudes of several thousand kilometers. At the same time DE-2 was placed into a polar orbit, coplanar with that of DE-1 but with a perigee altitude low enough (309 km) for neutral measurements and an apogee altitude of 1012 km. The DE-1 High Altitude Plasma Instrument (HAPI) provided data on low and medium energy electrons and ions from August 13, 1981 until December 1, 1981, when a high-voltage failure occured. Analysis of HAPI data for the time period of this contract has produced new results on the source mechanisms for electron conical distributions, particle acceleration phenomena in auroral acceleration regions, Birkeland currents throughout the nightside auroral regions, the source region for auroral kilometric radiation (AKR), and plasma injection phenomena in the polar cusp.

  19. High Altitude Ozone Research Balloon

    NASA Technical Reports Server (NTRS)

    Cauthen, Timothy A.; Daniel, Leslie A.; Herrick, Sally C.; Rock, Stacey G.; Varias, Michael A.

    1990-01-01

    In order to create a mission model of the high altitude ozone research balloon (HAORB) several options for flight preparation, altitude control, flight termination, and payload recovery were considered. After the optimal launch date and location for two separate HAORB flights were calculated, a method for reducing the heat transfer from solar and infrared radiation was designed and analytically tested. This provided the most important advantage of the HAORB over conventional balloons, i.e., its improved flight duration. Comparisons of different parachute configurations were made, and a design best suited for the HAORB's needs was determined to provide for payload recovery after flight termination. In an effort to avoid possible payload damage, a landing system was also developed.

  20. Effects of low-grade hypoxia on performance in a vigilance situation.

    DOT National Transportation Integrated Search

    1971-03-01

    Forty male subjects participated in a study to examine the relationship between low-grade hypoxia and vigilance performance. At an altitude equivalent of 11,500 feet in a low-pressure chamber, subjects without supplemental oxygen did not respond diff...

  1. Long-Term Exposure to High Altitude Affects Conflict Control in the Conflict-Resolving Stage

    PubMed Central

    Wu, Jianhui; Wang, Baoxi; Guo, Shichun; Luo, Ping; Han, Buxin

    2015-01-01

    The neurocognitive basis of the effect of long-term high altitude exposure on conflict control is unclear. Event related potentials (ERPs) were recorded in a flanker task to investigate the influence of high altitude on conflict control in the high-altitude group (who had lived at high altitude for three years but were born at low altitude) and the low-altitude group (living in low altitude only). Although altitude effect was not significant at the behavioral level, ERPs showed cognitive conflict modulation. The interaction between group and trial type was significant: P3 amplitude was greater in the low-altitude group than in the high-altitude group in the incongruent trial. This result suggests that long-term exposure to high altitude affects conflict control in the conflict-resolving stage, and that attentional resources are decreased to resist the conflict control in the high-altitude group. PMID:26671280

  2. Shape memory alloy resistance behaviour at high altitude for feedback control

    NASA Astrophysics Data System (ADS)

    Ng, W. T.; Sedan, M. F.; Abdullah, E. J.; Azrad, S.; Harithuddin, A. S. M.

    2017-12-01

    Many recent aerospace technologies are using smart actuators to reduce the system's complexity and increase its reliability. One such actuator is shape memory alloy (SMA) actuator, which is lightweight, produces high force and large deflection. However, some disadvantages in using SMA actuators have been identified and they include nonlinear response of the strain to input current, hysteresis characteristic that results in inaccurate control and less than optimum system performance, high operating temperatures, slow response and also high requirement of electrical power to obtain the desired actuation forces. It is still unknown if the SMA actuators can perform effectively at high altitude with low surrounding temperature. The work presented here covers the preliminary process of verifying the feasibility of using resistance as feedback control at high altitude for aerospace applications. Temperature and resistance of SMA actuator at high altitude is investigated by conducting an experiment onboard a high altitude balloon. The results from the high altitude experiment indicate that the resistance or voltage drop of the SMA wire is not significantly affected by the low surrounding temperature at high altitude as compared to the temperature of SMA. Resistance feedback control for SMA actuators may be suitable for aerospace applications.

  3. Altitude exposures during commercial flight: a reappraisal.

    PubMed

    Hampson, Neil B; Kregenow, David A; Mahoney, Anne M; Kirtland, Steven H; Horan, Kathleen L; Holm, James R; Gerbino, Anthony J

    2013-01-01

    Hypobaric hypoxia during commercial air travel has the potential to cause or worsen hypoxemia in individuals with pre-existing cardiopulmonary compromise. Knowledge of cabin altitude pressures aboard contemporary flights is essential to counseling patients accurately about flying safety. The objective of the study was to measure peak cabin altitudes during U.S. domestic commercial flights on a variety of aircraft. A handheld mountaineering altimeter was carried by the investigators in the plane cabin during commercial air travel and peak cabin altitude measured. The values were then compared between aircraft models, aircraft classes, and distances flown. The average peak cabin altitude on 207 flights aboard 17 different aircraft was 6341 +/- 1813 ft (1933 m +/- 553 m), significantly higher than when measured in a similar fashion in 1988. Peak cabin altitude was significantly higher for flights longer than 750 mi (7085 +/- 801 ft) compared to shorter flights (5160 +/- 2290 ft/1573 +/- 698 m). Cabin altitude increased linearly with flight distance for flights up to 750 mi in length, but was independent of flight distance for flights exceeding 750 mi. Peak cabin altitude was less than 5000 ft (1524 m) in 70% of flights shorter than 500 mi. Peak cabin altitudes greater than 8000 ft (2438 m) were measured on approximately 10% of the total flights. Peak cabin altitude on commercial aircraft flights has risen over time. Cabin altitude is lower with flights of shorter distance. Physicians should take these factors into account when determining an individual's need for supplemental oxygen during commercial air travel.

  4. Effects of acute moderate hypoxia on anaerobic capacity in endurance-trained runners.

    PubMed

    Friedmann, Birgit; Frese, Falko; Menold, Elmar; Bärtsch, Peter

    2007-09-01

    While there is some controversy whether anaerobic capacity might be improved after altitude training little is known about changes in anaerobic capacity during hypoxic exposure in highly trained athletes. In order to analyze the effects of acute moderate normobaric hypoxia on anaerobic capacity, 18 male competitive triathletes, middle- and long-distance runners VO2max 67.4 +/- 3.8 ml kg min(-1) performed 2 supra-VO2max treadmill runs with the same speed, one in normoxia and one after 4 h exposure to normobaric hypoxia (FiO(2) 0.15), for estimation of their maximal accumulated oxygen deficit (MAOD) and measurement of peak capillary lactate and peak capillary ammonia concentration. MAOD was not significantly different in normoxia and in moderate hypoxia while time to exhaustion and accumulated O(2) uptake were significantly (P < 0.001) reduced in hypoxia compared to normoxia by 28 and 45%, respectively. The reduction in time to exhaustion was significantly correlated to the decrement in accumulated O(2) uptake (R = 0.730, P = 0.001). In hypoxia, there was a tendency for peak capillary lactate concentration to be decreased compared to normoxia (12.9 +/- 2.1 vs. 13.8 +/- 2.2 mmol l(-1), P = 0.082); peak capillary ammonia concentration was significantly decreased in hypoxia (97 +/- 52 vs. 121 +/- 44 micromol l(-1), P = 0.032). In conclusion, anaerobic capacity is not significantly changed during acute exposure to moderate hypoxia in endurance-trained athletes. The performance reduction during all-out exercise of short duration has to be attributed to the decrement in aerobic capacity.

  5. Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway.

    PubMed

    He, Y; Jian, C X; Zhang, H Y; Zhou, Y; Wu, X; Zhang, G; Tan, Y H

    2016-11-21

    There is high incidence of periodontal disease in high-altitude environments; hypoxia may influence the proliferation and clone-forming ability of periodontal ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated with cell proliferation, differentiation, and apoptosis. Thus, we isolated and cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on PDLSC proliferation and the underlying mechanism. PDLSCs were separated and purified by the limiting dilution method and identified by flow cytometry. PDLSCs were cultured under hypoxic or normoxic conditions to observe their cloning efficiency. PDLSC proliferation at different oxygen concentrations was evaluated by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to PDLSCs to observe their impacts on clone formation and proliferation. Isolated PDLSCs exhibited typical stem cell morphological characteristics, strong abilities of globular clone formation and proliferation, and upregulated expression of mesenchymal stem cell markers. Stem cell marker expression was not statistically different between PDLSCs cultured under hypoxia and normoxia (P > 0.05). The clone number in the hypoxia group was significantly higher than that in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK inhibitor or ERK inhibitor treatment reduced clone formation and proliferation. Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating the p38/MAPK and ERK/MAPK signaling pathways.

  6. Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

    PubMed Central

    Janecka, Jan E.; Nielsen, Simone S. E.; Andersen, Sidsel D.; Hoffmann, Federico G.; Weber, Roy E.; Anderson, Trevor; Storz, Jay F.; Fago, Angela

    2015-01-01

    ABSTRACT Genetically based modifications of hemoglobin (Hb) function that increase blood–O2 affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O2 affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood–O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation that may contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O2 affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O2 affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O2-transport pathway. PMID:26246610

  7. Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard.

    PubMed

    Janecka, Jan E; Nielsen, Simone S E; Andersen, Sidsel D; Hoffmann, Federico G; Weber, Roy E; Anderson, Trevor; Storz, Jay F; Fago, Angela

    2015-08-01

    Genetically based modifications of hemoglobin (Hb) function that increase blood-O2 affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O2 affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood-O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation that may contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O2 affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O2 affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O2-transport pathway. © 2015. Published by The Company of Biologists Ltd.

  8. Disease Threat at High Terrestrial Altitudes. Volume 1.

    DTIC Science & Technology

    1979-08-01

    transmit, the bite of a louse may produce an irritating dermatitis, pediculosis . Louseborne typhus is reported to be prevalent in the higher altitudes of...residents of the village. Pediculosis was present in 49.6% of the study population. A high incidence of body lice was also reported in Badrinth, India...altitude 3,200 meters and the prevalence of pediculosis was high. (4) Mosquito-borne Diseases Mosquitoes constitute the single most important family

  9. Moderate exercise increases endotoxin concentration in hypoxia but not in normoxia: A controlled clinical trial.

    PubMed

    Machado, Paola; Caris, Aline; Santos, Samile; Silva, Edgar; Oyama, Lila; Tufik, Sergio; Santos, Ronaldo

    2017-01-01

    Hypoxia and high altitudes affect various organs, which impairs important physiological functions, such as a disruption of the intestinal barrier mediated by increased translocation of bacteria and increased circulating endotoxin levels. Physical exercise can alter endotoxin concentration in normoxia. The aim of this study is to evaluate the effects of moderate exercise on endotoxin concentration in normobaric hypoxia. Nine healthy male volunteers exercised on a treadmill for 60 minutes at an intensity of 50% VO2peak in normoxic or hypoxic conditions (4200 m). Blood was collected at rest, immediately after exercise and 1 hour after exercise to evaluate serum endotoxin levels. Under hypoxic exercise conditions, SaO2% saturation was lower after exercise compared with resting levels (P < 0.05) and returned to the resting level during recovery in normoxia (P < 0.05). Endotoxin concentration increased after exercise in hypoxia (P < 0.05); it remained high 1 hour after exercise in hypoxia compared with normoxia (P < 0.05) and was higher after exercise and recovery compared with resting levels (P < 0.05). HR was higher during exercise in relation basal in both conditions (P < 0.05) and RPR increase after 60 minutes in comparison to 20 minutes in hypoxia (P < 0.05). Moderate exercise performed in hypoxia equivalent to 4200 m increased endotoxin plasma concentration after exercise. One hour of rest in normoxic conditions was insufficient for the recovery of circulating endotoxins.

  10. Exploring the Limits of High Altitude GPS for Future Lunar Missions

    NASA Technical Reports Server (NTRS)

    Ashman, Benjamin W.; Parker, Joel J.; Bauer, Frank H.; Esswein, Michael

    2018-01-01

    An increasing number of spacecraft are relying on the Global Positioning System (GPS) for navigation at altitudes near or above the GPS constellation itself - the region known as the Space Service Volume (SSV). While the formal definition of the SSV ends at geostationary altitude, the practical limit of high-altitude space usage is not known, and recent missions have demonstrated that signal availability is sufficient for operational navigation at altitudes halfway to the moon. This paper presents simulation results based on a high-fidelity model of the GPS constellation, calibrated and validated through comparisons of simulated GPS signal availability and strength with flight data from recent high-altitude missions including the Geostationary Operational Environmental Satellite 16 (GOES-16) and the Magnetospheric Multiscale (MMS) mission. This improved model is applied to the transfer to a lunar near-rectilinear halo orbit (NRHO) of the class being con- sidered for the international Deep Space Gateway concept. The number of GPS signals visible and their received signal strengths are presented as a function of receiver altitude in order to explore the practical upper limit of high-altitude space usage of GPS.

  11. Exploring the Limits of High Altitude GPS for Future Lunar Missions

    NASA Technical Reports Server (NTRS)

    Ashman, Benjamin W.; Parker, Joel J. K.; Bauer, Frank H.; Esswein, Michael

    2018-01-01

    An increasing number of spacecraft are relying on the Global Positioning System (GPS) for navigation at altitudes near or above the GPS constellation itself - the region known as the Space Service Volume (SSV). While the formal definition of the SSV ends at geostationary altitude, the practical limit of high-altitude space usage is not known, and recent missions have demonstrated that signal availability is sufficient for operational navigation at altitudes halfway to the moon. This paper presents simulation results based on a high-fidelity model of the GPS constellation, calibrated and validated through comparisons of simulated GPS signal availability and strength with flight data from recent high-altitude missions including the Geostationary Operational Environmental Satellite 16 (GOES-16) and the Magnetospheric Multiscale (MMS) mission. This improved model is applied to the transfer to a lunar near-rectilinear halo orbit (NRHO) of the class being considered for the international Deep Space Gateway concept. The number of GPS signals visible and their received signal strengths are presented as a function of receiver altitude in order to explore the practical upper limit of high-altitude space usage of GPS.

  12. AltitudeOmics: Resetting of Cerebrovascular CO2 Reactivity Following Acclimatization to High Altitude

    PubMed Central

    Fan, Jui-Lin; Subudhi, Andrew W.; Duffin, James; Lovering, Andrew T.; Roach, Robert C.; Kayser, Bengt

    2016-01-01

    Previous studies reported enhanced cerebrovascular CO2 reactivity upon ascent to high altitude using linear models. However, there is evidence that this response may be sigmoidal in nature. Moreover, it was speculated that these changes at high altitude are mediated by alterations in acid-base buffering. Accordingly, we reanalyzed previously published data to assess middle cerebral blood flow velocity (MCAv) responses to modified rebreathing at sea level (SL), upon ascent (ALT1) and following 16 days of acclimatization (ALT16) to 5260 m in 21 lowlanders. Using sigmoid curve fitting of the MCAv responses to CO2, we found the amplitude (95 vs. 129%, SL vs. ALT1, 95% confidence intervals (CI) [77, 112], [111, 145], respectively, P = 0.024) and the slope of the sigmoid response (4.5 vs. 7.5%/mmHg, SL vs. ALT1, 95% CIs [3.1, 5.9], [6.0, 9.0], respectively, P = 0.026) to be enhanced at ALT1, which persisted with acclimatization at ALT16 (amplitude: 177, 95% CI [139, 215], P < 0.001; slope: 10.3%/mmHg, 95% CI [8.2, 12.5], P = 0.003) compared to SL. Meanwhile, the sigmoidal response midpoint was unchanged at ALT1 (SL: 36.5 mmHg; ALT1: 35.4 mmHg, 95% CIs [34.0, 39.0], [33.1, 37.7], respectively, P = 0.982), while it was reduced by ~7 mmHg at ALT16 (28.6 mmHg, 95% CI [26.4, 30.8], P = 0.001 vs. SL), indicating leftward shift of the cerebrovascular CO2 response to a lower arterial partial pressure of CO2 (PaCO2) following acclimatization to altitude. Sigmoid fitting revealed a leftward shift in the midpoint of the cerebrovascular response curve which could not be observed with linear fitting. These findings demonstrate that there is resetting of the cerebrovascular CO2 reactivity operating point to a lower PaCO2 following acclimatization to high altitude. This cerebrovascular resetting is likely the result of an altered acid-base buffer status resulting from prolonged exposure to the severe hypocapnia associated with ventilatory acclimatization to high altitude. PMID:26779030

  13. Common High Altitudes Illnesses a Primer for Healthcare Provider

    PubMed Central

    Mohsenin, Vahid

    2015-01-01

    Exposure to high altitude imposes significant strain on cardiopulmonary system and the brain. As a consequence, sojourners to high altitude frequently experience sleep disturbances, often reporting restless and sleepless nights. At altitudes above 3,000 meters (9,800 ft) almost all healthy subjects develop periodic breathing especially during NREM sleep. Sleep architecture gradually improves with increased NREM and REM sleep despite persistence of periodic breathing. The primary reason for periodic breathing at high altitude is a hypoxic-induced increase in chemoreceptor sensitivity to changes in PaCO2 – both above and below eupnea, leading to periods of apnea and hyperpnea. Acetazolamide improves sleep by reducing the periodic breathing through development of metabolic acidosis and induced hyperventilation decreasing the plant gain and widening the PCO2 reserve. This widening of the PCO2 reserve impedes development of central apneas during sleep. Benzodiazepines and GABA receptor antagonist such as zolpidem improve sleep without affecting breathing pattern or cognitive functions. PMID:27057512

  14. Autophagy Is a Promoter for Aerobic Exercise Performance during High Altitude Training

    PubMed Central

    Zhang, Ying

    2018-01-01

    High altitude training is one of the effective strategies for improving aerobic exercise performance at sea level via altitude acclimatization, thereby improving oxygen transport and/or utilization. But its underlying molecular mechanisms on physiological functions and exercise performance of athletes are still vague. More recent evidence suggests that the recycling of cellular components by autophagy is an important process of the body involved in the adaptive responses to exercise. Whether high altitude training can activate autophagy or whether high altitude training can improve exercise performance through exercise-induced autophagy is still unclear. In this narrative review article, we will summarize current research advances in the improvement of exercise performance through high altitude training and its reasonable molecular mechanisms associated with autophagy, which will provide a new field to explore the molecular mechanisms of adaptive response to high altitude training. PMID:29849885

  15. Prediction of Critical Power and W' in Hypoxia: Application to Work-Balance Modelling.

    PubMed

    Townsend, Nathan E; Nichols, David S; Skiba, Philip F; Racinais, Sebastien; Périard, Julien D

    2017-01-01

    Purpose: Develop a prediction equation for critical power (CP) and work above CP (W') in hypoxia for use in the work-balance ([Formula: see text]) model. Methods: Nine trained male cyclists completed cycling time trials (TT; 12, 7, and 3 min) to determine CP and W' at five altitudes (250, 1,250, 2,250, 3,250, and 4,250 m). Least squares regression was used to predict CP and W' at altitude. A high-intensity intermittent test (HIIT) was performed at 250 and 2,250 m. Actual and predicted CP and W' were used to compute W' during HIIT using differential ([Formula: see text]) and integral ([Formula: see text]) forms of the [Formula: see text] model. Results: CP decreased at altitude ( P < 0.001) as described by 3rd order polynomial function ( R 2 = 0.99). W' decreased at 4,250 m only ( P < 0.001). A double-linear function characterized the effect of altitude on W' ( R 2 = 0.99). There was no significant effect of parameter input (actual vs. predicted CP and W') on modelled [Formula: see text] at 2,250 m ( P = 0.24). [Formula: see text] returned higher values than [Formula: see text] throughout HIIT ( P < 0.001). During HIIT, [Formula: see text] was not different to 0 kJ at completion, at 250 m (0.7 ± 2.0 kJ; P = 0.33) and 2,250 m (-1.3 ± 3.5 kJ; P = 0.30). However, [Formula: see text] was lower than 0 kJ at 250 m (-0.9 ± 1.3 kJ; P = 0.058) and 2,250 m (-2.8 ± 2.8 kJ; P = 0.02). Conclusion: The altitude prediction equations for CP and W' developed in this study are suitable for use with the [Formula: see text] model in acute hypoxia. This enables the application of [Formula: see text] modelling to training prescription and competition analysis at altitude.

  16. Health, Safety and Performance in High Altitude Observatories: A Sustainable Approach

    NASA Astrophysics Data System (ADS)

    Böcker, Michael; Vogt, Joachim; Christ, Oliver; Müller-Leonhardt, Alice

    2009-09-01

    The research project “Optimising Performance, Health and Safety in High Altitude Observatories” was initiated by ESO to establish an approach to promote the well-being of staff working at its high altitude observatories, and in particular at the Antiplano de Chajnantor. A survey by a questionnaire given to both workers and visitors was employed to assess the effects of working conditions at high altitude. Earlier articles have outlined the project and reported early results. The final results and conclusions are presented, together with a concept for sustainable development to improve the performance, health and safety at high altitude employing Critical Incident Stress Management.

  17. Cerebral Oxygenation in Awake Rats during Acclimation and Deacclimation to Hypoxia: An In Vivo Electron Paramagnetic Resonance Study

    PubMed Central

    Khan, Mohammad N.; Hou, Huagang G.; Merlis, Jennifer; Abajian, Michelle A.; Demidenko, Eugene; Grinberg, Oleg Y.; Swartz, Harold M.

    2011-01-01

    Abstract Dunn, J. F., N. Khan, H. G. Hou, J. Merlis, M. A. Abajian, E. Demidenko, O.Y. Grinberg, and H. M. Swartz. Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo EPR study. High Alt. Med. Biol. 12:71–77, 2011.— Exposure to high altitude or hypobaric hypoxia results in a series of metabolic, physiologic, and genetic changes that serve to acclimate the brain to hypoxia. Tissue Po2 (Pto2) is a sensitive index of the balance between oxygen delivery and utilization and can be considered to represent the summation of such factors as cerebral blood flow, capillary density, hematocrit, arterial Po2, and metabolic rate. As such, it can be used as a marker of the extent of acclimation. We developed a method using electron paramagnetic resonance (EPR) to measure Pto2 in unanesthetized subjects with a chronically implanted sensor. EPR was used to measure rat cortical tissue Pto2 in awake rats during acute hypoxia and over a time course of acclimation and deacclimation to hypobaric hypoxia. This was done to simulate the effects on brain Pto2 of traveling to altitude for a limited period. Acute reduction of inspired O2 to 10% caused a decline from 26.7 ± 2.2 to 13.0 ± 1.5 mmHg (mean ± SD). Addition of 10% CO2 to animals breathing 10% O2 returned Pto2 to values measured while breathing 21% O2, indicating that hypercapnia can reverse the effects of acute hypoxia. Pto2 in animals acclimated to 10% O2 was similar to that measured preacclimation when breathing 21% O2. Using a novel, individualized statistical model, it was shown that the T1/2 of the Pto2 response during exposure to chronic hypoxia was approximately 2 days. This indicates a capacity for rapid adaptation to hypoxia. When subjects were returned to normoxia, there was a transient hyperoxygenation, followed by a return to lower values with a T1/2 of deacclimation of 1.5 to 3 days. These data indicate that exposure to hypoxia results in significant

  18. PH2O and simulated hypobaric hypoxia.

    PubMed

    Conkin, Johnny

    2011-12-01

    Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F1O2 < 0.209 at or near sea level pressure to match the ambient oxygen partial pressure (iso-PO2) of the target altitude. I conclude after a review of literature from investigators and manufacturers that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of oxygen (P1O2), which is substantial at higher altitude relative to sea level. Consequently, some devices claiming an equivalent HH experience under normobaric conditions would significantly overestimate the HH condition, especially when simulating altitudes above 10,000 ft (3048 m). At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient PO2 at sea level as at altitude. An approach to reduce the overestimation and standardize the operation is to at least provide machines that create the same P1O2 conditions at sea level as at the target altitude, a simple software upgrade.

  19. Glucose Homeostasis During Short-term and Prolonged Exposure to High Altitudes

    PubMed Central

    Ader, Marilyn; Bergman, Richard N.

    2015-01-01

    Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis. PMID:25675133

  20. Genetic and phenotypic differentiation of an Andean intermediate altitude population

    PubMed Central

    Eichstaedt, Christina A; Antão, Tiago; Cardona, Alexia; Pagani, Luca; Kivisild, Toomas; Mormina, Maru

    2015-01-01

    Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaquíes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wichí population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample (n = 74) and performed various scans for positive selection. At the phenotypic level (n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaquíes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures. PMID:25948820

  1. History of Migraine Predicts Headache at High Altitude.

    PubMed

    Davis, Christopher; Reno, Elaine; Maa, Edward; Roach, Robert

    2016-12-01

    Davis, Christopher, Elaine Reno, Edward Maa, and Robert Roach. History of Migraine Predicts Headache at High Altitude. High Alt Med Biol. 17:300-304, 2016.-Objective: To characterize the spectrum of headaches and their association with migraine history within a population of recreational hikers above 4300 m. Using a cross-sectional survey design, a convenience sample of 667 hikers participated in a written survey after descent from Mount Gray/Torreys (4349 m). Headaches were characterized as migraine, high altitude headache (HAH), and/or acute mountain sickness (AMS) using International Headache Society Lake Louise AMS scoring criteria. A univariate odds ratio was calculated to determine whether a history of migraine increased the risk of migrainous headache. Multivariate logistic regression was used to assess whether a priori identified risk factors such as age, sex, recent alcohol consumption, home elevation, and self-reported fluid intake and whether summit success increased the risk of any headache at altitude. Sixty percent of hikers were male with an age range of 17-62 years. Eighty percent reached the summit of Mount Grays/Torreys (4349 m). Seventy-nine percent of participants resided in Colorado; the median elevation of residence for subjects was 1697 m (interquartile range 1557-1765 m). HAH occurred in 39% of hikers, while AMS occurred in 26% of hikers. A history of migraine was associated with increased risk of any headache at altitude (OR: 2.49, 95% CI: 1.62-3.65) and was strongly associated with the development of migrainous headache while at altitude (OR: 14.05, 95% CI: 5.49-35.93). A history of migraine is a risk factor for the development of headache at altitude and is strongly associated with the development of migrainous headache.

  2. High-Altitude, Long-Endurance Airships for Coastal Surveillance

    NASA Technical Reports Server (NTRS)

    Dolce, James L.; Collozza, Anthony

    2005-01-01

    A high altitude solar powered airship provides the ability to carry large payloads to high altitudes and remain on station for extended periods of time. This study examines applications and background of this type of concept vehicle, reviews the history of high altitude flight and provides a point design analysis. The capabilities and limitations of the airship are demonstrated and possible solutions are proposed. Factors such as time of year, latitude, wind speeds, and payload are considered in establishing the capabilities of the airship. East and west coast operation is evaluated. The key aspect to success of this type of airship is the design and operation of the propulsion and power system. A preliminary propulsion/power system design was produced based on a regenerative fuel cell energy storage system and solar photovoltaic array for energy production. Results on power system requirements for year long operation is presented.

  3. Effects of intermittent hypoxia on running economy.

    PubMed

    Burtscher, M; Gatterer, H; Faulhaber, M; Gerstgrasser, W; Schenk, K

    2010-09-01

    We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy (RE). 11 male and female middle-distance runners were randomly assigned to the intermittent hypoxia group (IHG) or to the control group (CG). All athletes trained for a 13-wk period starting at pre-season until the competition season. The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia (15-11% FiO2). RE, haematological parameters and body composition were determined at low altitude (600 m) at baseline, after the 5 (th), the 8 (th) and the 13 (th) week of training. RE, determined by the relative oxygen consumption during submaximal running, (-2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg, P<0.05) and total running time (+1.0+/-0.9 vs. +0.4+/-0.5 min, P<0.05) changed significantly between the IHG and CG only during the first 5-wk period. Haematological and cardiorespiratory changes indicate that the improved RE was associated with decreased cardiorespiratory costs and greater reliance on carbohydrate. Intermittent hypoxia did not affect RE during the second 5-wk period. These findings suggest that the effects of intermittent hypoxia on RE strongly depend on the training phase. Georg Thieme Verlag KG Stuttgart . New York.

  4. Doppler recordings after diving to depth of 30 meters at high altitude of 4,919 meters (16,138 feet) during the Tilicho Lake Expedition 2007.

    PubMed

    Kot, J; Sicko, Z; Zyszkowski, M; Brajta, M

    2014-01-01

    When going to high altitude (higher than 2,400 meters above mean sea level [about 8,200 feet]), human physiology is strongly affected by changes in atmospheric conditions, including decreased ambient pressure and hypobaric hypoxia, which can lead to severe hypoxemia, brain and/or pulmonary edema, negative changes in body and blood composition, as well as disturbances in regional microcirculation. When adding other factors, such as dehydration, physical exercise and exposure to low temperature, it is likely that nitrogen desaturation after diving at such environmental conditions is far from optimal, There are only single reports on diving at high alti-tudes. In 2007 a Polish team of climbers and divers participated in the Tilicho Lake and Peak Expedition to the Himalaya Mountains in Nepal. During this expedition, four divers conducted six dives in the Tilicho Lake at altitude of 4,919 meters above mean sea level equivalent (16,138 feet) to a maximum depth of 15 meters of fresh water (mfw) (equivalent to 28 mfw at sea level by the Cross Correction method) and 30 mfw (equivalent to 57 mfw at sea level "by Cross correction). Decompression debt was calculated using Cross Correction with some additional safety add-ons. Precordial Doppler recordings were taken every 15 minutes until 90 minutes after surfacing. No signs or symptoms of decompression sickness were observed after diving but in one diver, very high bubble grade Doppler signals were recorded. It can be concluded that diving at high altitude should be accompanied by additional safety precautions as well as taking into account personal sensitivity for such conditions.

  5. HypoxiaDB: a database of hypoxia-regulated proteins

    PubMed Central

    Khurana, Pankaj; Sugadev, Ragumani; Jain, Jaspreet; Singh, Shashi Bala

    2013-01-01

    There has been intense interest in the cellular response to hypoxia, and a large number of differentially expressed proteins have been identified through various high-throughput experiments. These valuable data are scattered, and there have been no systematic attempts to document the various proteins regulated by hypoxia. Compilation, curation and annotation of these data are important in deciphering their role in hypoxia and hypoxia-related disorders. Therefore, we have compiled HypoxiaDB, a database of hypoxia-regulated proteins. It is a comprehensive, manually-curated, non-redundant catalog of proteins whose expressions are shown experimentally to be altered at different levels and durations of hypoxia. The database currently contains 72 000 manually curated entries taken on 3500 proteins extracted from 73 peer-reviewed publications selected from PubMed. HypoxiaDB is distinctive from other generalized databases: (i) it compiles tissue-specific protein expression changes under different levels and duration of hypoxia. Also, it provides manually curated literature references to support the inclusion of the protein in the database and establish its association with hypoxia. (ii) For each protein, HypoxiaDB integrates data on gene ontology, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, protein–protein interactions, protein family (Pfam), OMIM (Online Mendelian Inheritance in Man), PDB (Protein Data Bank) structures and homology to other sequenced genomes. (iii) It also provides pre-compiled information on hypoxia-proteins, which otherwise requires tedious computational analysis. This includes information like chromosomal location, identifiers like Entrez, HGNC, Unigene, Uniprot, Ensembl, Vega, GI numbers and Genbank accession numbers associated with the protein. These are further cross-linked to respective public databases augmenting HypoxiaDB to the external repositories. (iv) In addition, HypoxiaDB provides an online sequence-similarity search tool for

  6. High altitude gust acceleration environment as experienced by a supersonic airplane

    NASA Technical Reports Server (NTRS)

    Ehernberger, L. J.; Love, B. J.

    1975-01-01

    High altitude turbulence experienced at supersonic speeds is described in terms of gust accelerations measured on the YF-12A airplane. The data were obtained during 90 flights at altitudes above 12.2 kilometers (40,000 feet). Subjective turbulence intensity ratings were obtained from air crew members. The air crew often rated given gust accelerations as being more intense during high altitude supersonic flight than during low altitude subsonic flight. The portion of flight distance in turbulence ranged from 6 percent to 8 percent at altitudes between 12.2 kilometers and 16.8 kilometers (40,000 feet and 55,000 feet) to less than 1 percent at altitudes above 18.3 kilometers (60,000 feet). The amount of turbulence varied with season, increasing by a factor of 3 or more from summer to winter. Given values of gust acceleration were less frequent, on the basis of distance traveled, for supersonic flight of the YF-12A airplane at altitudes above 12.2 kilometers (40,000 feet) than for subsonic flight of a jet passenger airplane at altitudes below 12.2 kilometers (40,000 feet). The median thickness of high altitude turbulence patches was less than 400 meters (1300 feet); the median length was less than 16 kilometers (10 miles). The distribution of the patch dimensions tended to be log normal.

  7. Effects of Carbohydrate and Glutamine Supplementation on Oral Mucosa Immunity after Strenuous Exercise at High Altitude: A Double-Blind Randomized Trial

    PubMed Central

    Caris, Aline Venticinque; Da Silva, Edgar Tavares; Dos Santos, Samile Amorim; Tufik, Sergio

    2017-01-01

    This study analyzed the effects of carbohydrate and glutamine supplementation on salivary immunity after exercise at a simulated altitude of 4500 m. Fifteen volunteers performed exercise of 70% of VO2peak until exhaustion and were divided into three groups: hypoxia placebo, hypoxia 8% maltodextrin (200 mL/20 min), and hypoxia after six days glutamine (20 g/day) and 8% maltodextrin (200 mL/20 min). All procedures were randomized and double-blind. Saliva was collected at rest (basal), before exercise (pre-exercise), immediately after exercise (post-exercise), and two hours after exercise. Analysis of Variance (ANOVA) for repeated measures and Tukey post hoc test were performed. Statistical significance was set at p < 0.05. SaO2% reduced when comparing baseline vs. pre-exercise, post-exercise, and after recovery for all three groups. There was also a reduction of SaO2% in pre-exercise vs. post-exercise for the hypoxia group and an increase was observed in pre-exercise vs. recovery for both supplementation groups, and between post-exercise and for the three groups studied. There was an increase of salivary flow in post-exercise vs. recovery in Hypoxia + Carbohydrate group. Immunoglobulin A (IgA) decreased from baseline vs. post-exercise for Hypoxia + Glutamine group. Interleukin 10 (IL-10) increased from post-exercise vs. after recovery in Hypoxia + Carbohydrate group. Reduction of tumor necrosis factor alpha (TNF-α) was observed from baseline vs. post-exercise and after recovery for the Hypoxia + Carbohydrate group; a lower concentration was observed in pre-exercise vs. post-exercise and recovery. TNF-α had a reduction from baseline vs. post-exercise for both supplementation groups, and a lower secretion between baseline vs. recovery, and pre-exercise vs. post-exercise for Hypoxia + Carbohydrate group. Five hours of hypoxia and exercise did not change IgA. Carbohydrates, with greater efficiency than glutamine, induced anti-inflammatory responses. PMID:28671626

  8. Effects of Dietary Nitrate Supplementation on Physiological Responses, Cognitive Function, and Exercise Performance at Moderate and Very-High Simulated Altitude

    PubMed Central

    Shannon, Oliver M.; Duckworth, Lauren; Barlow, Matthew J.; Deighton, Kevin; Matu, Jamie; Williams, Emily L.; Woods, David; Xie, Long; Stephan, Blossom C. M.; Siervo, Mario; O'Hara, John P.

    2017-01-01

    Purpose: Nitric oxide (NO) bioavailability is reduced during acute altitude exposure, contributing toward the decline in physiological and cognitive function in this environment. This study evaluated the effects of nitrate (NO3−) supplementation on NO bioavailability, physiological and cognitive function, and exercise performance at moderate and very-high simulated altitude. Methods:Ten males (mean (SD): V˙O2max: 60.9 (10.1) ml·kg−1·min−1) rested and performed exercise twice at moderate (~14.0% O2; ~3,000 m) and twice at very-high (~11.7% O2; ~4,300 m) simulated altitude. Participants ingested either 140 ml concentrated NO3−-rich (BRJ; ~12.5 mmol NO3−) or NO3−-deplete (PLA; 0.01 mmol NO3−) beetroot juice 2 h before each trial. Participants rested for 45 min in normobaric hypoxia prior to completing an exercise task. Exercise comprised a 45 min walk at 30% V˙O2max and a 3 km time-trial (TT), both conducted on a treadmill at a 10% gradient whilst carrying a 10 kg backpack to simulate altitude hiking. Plasma nitrite concentration ([NO2−]), peripheral oxygen saturation (SpO2), pulmonary oxygen uptake (V˙O2), muscle and cerebral oxygenation, and cognitive function were measured throughout. Results: Pre-exercise plasma [NO2−] was significantly elevated in BRJ compared with PLA (p = 0.001). Pulmonary V˙O2 was reduced (p = 0.020), and SpO2 was elevated (p = 0.005) during steady-state exercise in BRJ compared with PLA, with similar effects at both altitudes. BRJ supplementation enhanced 3 km TT performance relative to PLA by 3.8% [1,653.9 (261.3) vs. 1718.7 (213.0) s] and 4.2% [1,809.8 (262.0) vs. 1,889.1 (203.9) s] at 3,000 and 4,300 m, respectively (p = 0.019). Oxygenation of the gastrocnemius was elevated during the TT consequent to BRJ (p = 0.011). The number of false alarms during the Rapid Visual Information Processing Task tended to be lower with BRJ compared with PLA prior to altitude exposure (p = 0.056). Performance in all other cognitive

  9. High altitude medicine education in China: exploring a new medical education reform.

    PubMed

    Luo, Yongjun; Luo, Rong; Li, Weiming; Huang, Jianjun; Zhou, Qiquan; Gao, Yuqi

    2012-03-01

    China has the largest plateau in the world, which includes the whole of Tibet, part of Qinghai, Xinjiang, Yunnan, and Sichuan. The plateau area is about 257.2×10(4) km(2), which accounts for about 26.8% of the total area of China. According to data collected in 2006, approximately twelve million people were living at high altitudes, between 2200 to 5200 m high, on the Qinghai-Tibetan Plateau. Therefore, there is a need for medical workers who are trained to treat individuals living at high altitudes. To train undergraduates in high altitude medicine, the College of High Altitude Military Medicine was set up at the Third Military Medical University (TMMU) in Chongqing in 1999. This is the only school to teach high altitude medicine in China. Students at TMMU study natural and social sciences, basic medical sciences, clinical medical sciences, and high altitude medicine. In their 5(th) year, students work as interns at the General Hospital of Tibet Military Command in Lhasa for 3 months, where they receive on-site teaching. The method of on-site teaching is an innovative approach for training in high altitude medicine for undergraduates. Three improvements were implemented during the on-site teaching component of the training program: (1) standardization of the learning progress; (2) integration of formal knowledge with clinical experience; and (3) coaching students to develop habits of inquiry and to engage in ongoing self-improvement to set the stage for lifelong learning. Since the establishment of the innovative training methods in 2001, six classes of high altitude medicine undergraduates, who received on-site teaching, have graduated and achieved encouraging results. This evidence shows that on-site teaching needs to be used more widely in high altitude medicine education.

  10. Heart rate and respiratory rhythm dynamics on ascent to high altitude

    NASA Technical Reports Server (NTRS)

    Lipsitz, L. A.; Hashimoto, F.; Lubowsky, L. P.; Mietus, J.; Moody, G. B.; Appenzeller, O.; Goldberger, A. L.

    1995-01-01

    OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress.

  11. Respiratory gas exchange of high altitude adapted chick embryos

    NASA Technical Reports Server (NTRS)

    Wangensteen, O. D.; Rahn, H.; Burton, R. R.; Smith, A. H.

    1974-01-01

    Study of gas exchange by embryos from chickens acclimatized to an altitude of 3800 m. The oxygen partial pressure and carbon dioxide partial pressure differences across the egg shell were measured and found to be less than the values previously reported for sea-level eggs by about a factor of two. Further measurements of embryonic oxygen consumption and shell conductivity to oxygen indicated that, compared to eggs at sea level, oxygen consumption was reduced by a factor of 0.58 while conductivity to oxygen was increased only by a factor of 1.07 in the high-altitude eggs. These independent measurements predict the change in oxygen partial pressure across the egg shell of the high-altitude eggs to be only 0.54 times that of sea-level eggs; the directly measured factor was 0.53. The authors conclude that at high altitude, a major adaptation of the chick embryo is a reduced metabolism which decreases the change in oxygen partial pressure across the egg shell since its gas conductivity remains essentially unchanged.

  12. The Effects of Differing Oxygen Concentrations on Reaction Time Performance at Altitude

    DTIC Science & Technology

    2014-12-04

    49, 943-946. Harding, R. M., Mills, F. J. (1983). Problems of altitude: Hypoxia and hyperventilation . British Medical Journal, 286, 1408-1410...K. P., Schippers, N., & Van den Bergh, O. (2000). Hyperventilation and attention: effects of hypocapnia on performance in a Stroop task. Biological

  13. Different hematologic responses to hypoxia in Sherpas and Quechua Indians.

    PubMed

    Winslow, R M; Chapman, K W; Gibson, C C; Samaja, M; Monge, C C; Goldwasser, E; Sherpa, M; Blume, F D; Santolaya, R

    1989-04-01

    Previous studies of the erythropoietic response to hypoxia in high-altitude natives suggest that the hematocrit and hemoglobin values in Himalayan natives (Sherpas) are lower than expected for the altitude, perhaps because of a genetic adaptation. However, differences in sampling techniques and experimental methods make comparisons difficult. Our studies were carried out to compare the erythropoietic response with the same altitude in age-matched natives of the Himalayas and Andes by the same experimental techniques. Healthy male subjects were selected in Ollagüe, Chile (n = 29, 27.3 +/- 5.9 yr) and in Khunde, Nepal (n = 30, 24.7 +/- 3.8 yr). Both of these villages are located at 3,700 m above sea level. Hematologic measurements confirmed lower hematocrit values in Nepal (48.4 +/- 4.5%) than in Chile (52.2 +/- 4.6%) (P less than 0.003). When subjects were matched for hematocrit, erythropoietin concentrations in Chile were higher than in Nepal (P less than 0.01). Detailed measurements of blood O2 affinity in Nepal showed no differences in shape or position of the O2 equilibrium curve between Sherpas and Western sojourners. Our results indicate that although Quechua Indians have higher hematocrits than Sherpas living at the same altitude, nevertheless they may be functionally anemic.

  14. Effects on Task Performance and Psychophysiological Measures of Performance During Normobaric Hypoxia Exposure

    NASA Technical Reports Server (NTRS)

    Stephens, Chad; Kennedy, Kellie; Napoli, Nicholas; Demas, Matthew; Barnes, Laura; Crook, Brenda; Williams, Ralph; Last, Mary Carolyn; Schutte, Paul

    2017-01-01

    Human-autonomous systems have the potential to mitigate pilot cognitive impairment and improve aviation safety. A research team at NASA Langley conducted an experiment to study the impact of mild normobaric hypoxia induction on aircraft pilot performance and psychophysiological state. A within-subjects design involved non-hypoxic and hypoxic exposures while performing three 10-minute tasks. Results indicated the effect of 15,000 feet simulated altitude did not induce significant performance decrement but did produce increase in perceived workload. Analyses of psychophysiological responses evince the potential of biomarkers for hypoxia onset. This study represents on-going work at NASA intending to add to the current knowledge of psychophysiologically-based input to automation to increase aviation safety. Analyses involving coupling across physiological systems and wavelet transforms of cortical activity revealed patterns that can discern between the simulated altitude conditions. Specifically, multivariate entropy of ECG/Respiration components were found to be significant predictors (p< 0.02) of hypoxia. Furthermore, in EEG, there was a significant decrease in mid-level beta (15.19-18.37Hz) during the hypoxic condition in thirteen of sixteen sites across the scalp. Task performance was not appreciably impacted by the effect of 15,000 feet simulated altitude. Analyses of psychophysiological responses evince the potential of biomarkers for mild hypoxia onset.The potential for identifying shifts in underlying cortical and physiological systems could serve as a means to identify the onset of deteriorated cognitive state. Enabling such assessment in future flightdecks could permit increasingly autonomous systems-supported operations. Augmenting human operator through assessment of cognitive impairment has the potential to further improve operator performance and mitigate human error in safety critical contexts. This study represents ongoing work at NASA intending to add

  15. Low-resolution ship detection from high-altitude aerial images

    NASA Astrophysics Data System (ADS)

    Qi, Shengxiang; Wu, Jianmin; Zhou, Qing; Kang, Minyang

    2018-02-01

    Ship detection from optical images taken by high-altitude aircrafts such as unmanned long-endurance airships and unmanned aerial vehicles has broad applications in marine fishery management, ship monitoring and vessel salvage. However, the major challenge is the limited capability of information processing on unmanned high-altitude platforms. Furthermore, in order to guarantee the wide detection range, unmanned aircrafts generally cruise at high altitudes, resulting in imagery with low-resolution targets and strong clutters suffered by heavy clouds. In this paper, we propose a low-resolution ship detection method to extract ships from these high-altitude optical images. Inspired by a recent research on visual saliency detection indicating that small salient signals could be well detected by a gradient enhancement operation combined with Gaussian smoothing, we propose the facet kernel filtering to rapidly suppress cluttered backgrounds and delineate candidate target regions from the sea surface. Then, the principal component analysis (PCA) is used to compute the orientation of the target axis, followed by a simplified histogram of oriented gradient (HOG) descriptor to characterize the ship shape property. Finally, support vector machine (SVM) is applied to discriminate real targets and false alarms. Experimental results show that the proposed method actually has high efficiency in low-resolution ship detection.

  16. Hypobaric Hypoxia Regulates Brain Iron Homeostasis in Rats.

    PubMed

    Li, Yaru; Yu, Peng; Chang, Shi-Yang; Wu, Qiong; Yu, Panpan; Xie, Congcong; Wu, Wenyue; Zhao, Baolu; Gao, Guofen; Chang, Yan-Zhong

    2017-06-01

    Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley (SD) rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after 4 weeks of treatment. We found that the iron levels significantly decreased in the cortex and hippocampus of rat brain as compared to that of the control rats without hypobaric hypoxia treatment. The expression levels of iron storage protein L-ferritin and iron transport proteins, including transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin1 (FPN1), were also altered. Further studies found that the iron regulatory protein 2 (IRP2) played a dominant regulatory role in the changes of iron hemostasis, whereas iron regulatory protein 1 (IRP1) mainly acted as cis-aconitase. These results, for the first time, showed the alteration of iron metabolism during hypobaric hypoxia in rat models, which link the potential neuroprotective role of hypobaric hypoxia treatment to the decreased iron level in brain. This may provide insight into the treatment of iron-overloaded neurodegenerative diseases. J. Cell. Biochem. 118: 1596-1605, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Effects of Hypobaric Hypoxia on Rat Retina and Protective Response of Resveratrol to the Stress

    PubMed Central

    Xin, Xiaorong; Dang, Hong; Zhao, Xiaojing; Wang, Haohao

    2017-01-01

    High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group. The hypoxia group and the resveratrol intervention group were maintained in a low-pressure oxygen cabin, and the resveratrol intervention group was given daily intraperitoneal injections with resveratrol. We found that hypobaric hypoxia increased thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) expression in retinas, and resveratrol treatment significantly reversed these changes (P < 0.05, P < 0.05 respectively). In comparison with controls, hypoxia upregulated the mRNA expression levels of caspase3 (P < 0.001), caspase9 (P < 0.01), heat shock protein 70 (Hsp70) (P < 0.05), heat shock protein 90 (Hsp90) (P < 0.001) and hypoxia-inducible factor-1 (HIF-1) (P < 0.05). Resveratrol administration caused a significant decrease in the gene expression of caspase3 (P< 0.001), HSP90 (P < 0.05) and HIF-1 mRNA (P < 0.01) as well as an increase in HSP70 mRNA when compared with the hypoxia group. These findings indicated that resveratrol exerted an anti-oxidative role by modulating hypoxia stress- associated genes and an anti-apoptosis role by regulating apoptosis-related cytokines. In conclusion, hypobaric hypoxia may have a pathological impact on rat retinas. The intervention of resveratrol reverses the effect induced by hypobaric hypoxia and elicits a protective response to the stress. PMID:28924365

  18. Effects of Hypobaric Hypoxia on Rat Retina and Protective Response of Resveratrol to the Stress.

    PubMed

    Xin, Xiaorong; Dang, Hong; Zhao, Xiaojing; Wang, Haohao

    2017-01-01

    High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group. The hypoxia group and the resveratrol intervention group were maintained in a low-pressure oxygen cabin, and the resveratrol intervention group was given daily intraperitoneal injections with resveratrol. We found that hypobaric hypoxia increased thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) expression in retinas, and resveratrol treatment significantly reversed these changes ( P < 0.05, P < 0.05 respectively). In comparison with controls, hypoxia upregulated the mRNA expression levels of caspase3 ( P < 0.001), caspase9 ( P < 0.01), heat shock protein 70 (Hsp70) ( P < 0.05), heat shock protein 90 (Hsp90) ( P < 0.001) and hypoxia-inducible factor-1 (HIF-1) ( P < 0.05). Resveratrol administration caused a significant decrease in the gene expression of caspase3 ( P < 0.001), HSP90 ( P < 0.05) and HIF-1 mRNA ( P < 0.01) as well as an increase in HSP70 mRNA when compared with the hypoxia group. These findings indicated that resveratrol exerted an anti-oxidative role by modulating hypoxia stress- associated genes and an anti-apoptosis role by regulating apoptosis-related cytokines. In conclusion, hypobaric hypoxia may have a pathological impact on rat retinas. The intervention of resveratrol reverses the effect induced by hypobaric hypoxia and elicits a protective response to the stress.

  19. Heart rate and respiratory rhythm dynamics on ascent to high altitude.

    PubMed Central

    Lipsitz, L. A.; Hashimoto, F.; Lubowsky, L. P.; Mietus, J.; Moody, G. B.; Appenzeller, O.; Goldberger, A. L.

    1995-01-01

    OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress. PMID:7488453

  20. Soft Contact Lens Wear at Altitude: Effects of Hypoxia

    DTIC Science & Technology

    1988-01-01

    conjunctiva (2). If the edema is severe, breakdown of some and aircraft with cabin pressures equivalent to lower altitudes, of the epithelial cells from...debris, conjunctival injection, and corneal epithelial of hydrogel lenses. International Contact Lens Clinic. 1983. staining, showed heightened...cornea may be severe enough to affect vision stnae accompanying the wearing of hydrogel lenses. Am. J. and preclude wearing soft contact lenses during

  1. Outdoor Activity and High Altitude Exposure During Pregnancy: A Survey of 459 Pregnancies.

    PubMed

    Keyes, Linda E; Hackett, Peter H; Luks, Andrew M

    2016-06-01

    To evaluate whether women engage in outdoor activities and high altitude travel during pregnancy; the health care advice received regarding high altitude during pregnancy; and the association between high altitude exposure and self-reported pregnancy complications. An online survey of women with at least 1 pregnancy distributed on websites and e-mail lists targeting mothers and/or mountain activities. Outcome measures were outdoor activities during pregnancy, high altitude (>2440 m) exposure during pregnancy, and pregnancy and perinatal complications. Hiking, running, and swimming were the most common activities performed during pregnancy. Women traveled to high altitude in over half of the pregnancies (244/459), and most did not receive counseling regarding altitude (355, 77%), although a small proportion (14, 3%) were told not to go above 2440 m. Rates of miscarriage and most other complications were similar between pregnancies with and without travel above 2440 m. Pregnancies with high altitude exposure were more likely to have preterm labor (odds ratio [OR] 2.3; 95% CI 0.97-5.4; P = .05). Babies born to women who went to high altitude during pregnancy were more likely to need oxygen at birth (OR 2.34; 95% CI 1.04-5.26; P < .05) but had similar rates of neonatal intensive care unit admission (P = not significant). Our results suggest pregnant women who are active in outdoor sports and travel to high altitude have a low rate of complications. Given the limitations of our data, further research is necessary on the risks associated with high altitude travel and physical activity and how these apply to the general population. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  2. Effect of Propranolol on Metabolic Responses to Exercise at High Altitude

    DTIC Science & Technology

    1988-02-01

    the low carbohydrate/ hypocaloric diet often assumed by altitude sojourners due to anorexia or ration restrictions. The results of the present...end of the altitude sojourn than at sea level. Although the subjects in this study consumed an ad libitum diet , they 15 were strongly encouraged to...consume a high carbohydrate diet particularly during the last five days at high altitude preceding the biopsy experiment. Dietary records were not kept

  3. Helicopter pilot scan techniques during low-altitude high-speed flight.

    PubMed

    Kirby, Christopher E; Kennedy, Quinn; Yang, Ji Hyun

    2014-07-01

    This study examined pilots' visual scan patterns during a simulated high-speed, low-level flight and how their scan rates related to flight performance. As helicopters become faster and more agile, pilots are expected to navigate at low altitudes while traveling at high speeds. A pilot's ability to interpret information from a combination of visual sources determines not only mission success, but also aircraft and crew survival. In a fixed-base helicopter simulator modeled after the U.S. Navy's MH-60S, 17 active-duty Navy helicopter pilots with varying total flight times flew and navigated through a simulated southern Californian desert course. Pilots' scan rate and fixation locations were monitored using an eye-tracking system while they flew through the course. Flight parameters, including altitude, were recorded using the simulator's recording system. Experienced pilots with more than 1000 total flight hours better maintained a constant altitude (mean altitude deviation = 48.52 ft, SD = 31.78) than less experienced pilots (mean altitude deviation = 73.03 ft, SD = 10.61) and differed in some aspects of their visual scans. They spent more time looking at the instrument display and less time looking out the window (OTW) than less experienced pilots. Looking OTW was associated with less consistency in maintaining altitude. Results may aid training effectiveness specific to helicopter aviation, particularly in high-speed low-level flight conditions.

  4. High-altitude medical and operations problems and solutions for the Millimeter Array

    NASA Astrophysics Data System (ADS)

    Napier, Peter J.; West, John B.

    1998-07-01

    The 5000m altitude of the potential site for the Millimeter Array (MMA) in Northern Chile is so high that high-altitude problems for both the staff and equipment must be considered and included in planing for the facility. The very good accessibility of the site, only one hour's drive from the nearest town at altitude 2440m, makes it possible for MMA workers to sleep and perform much of their work at low altitude. Workers on the site will have 11 percent less oxygen available than workers at Mauna Kea Observatory. It is expected that the mental abilities and ability to do hard physical labor of workers on the high site will be reduced by 10 percent to 30 percent compared to sea-level. In-doors working areas on the MMA site will have their atmospheres oxygen enriched to provide an effective working altitude of 3500m where loss of mental ability should be small. Tests of oxygen enrichment at high-altitude Chilean mines and at the University of California White Mountain Research Station show that it is feasible and economic. Problems of equipment operation at 5000m altitude are expected to be manageable.

  5. Electrocardiography in people living at high altitude of Nepal

    PubMed Central

    Aryal, Nirmal; Weatherall, Mark; Bhatta, Yadav Kumar Deo; Mann, Stewart

    2017-01-01

    Objective The main objective of this study was to estimate the prevalence of coronary heart disease (CHD) of high-altitude populations in Nepal determined by an ECG recordings and a medical history. Methods We carried out a cross-sectional survey of cardiovascular disease and risk factors among people living at four different altitude levels, all above 2800 m, in the Mustang and Humla districts of Nepal. 12-lead ECGs were recorded on 485 participants. ECG recordings were categorised as definitely abnormal, borderline or normal. Results No participant had Q waves to suggest past Q-wave infarction. Overall, 5.6% (95% CI 3.7 to 8.0) of participants gave a self-report of CHD. The prevalence of abnormal (or borderline abnormal) ECG was 19.6% (95% CI 16.1 to 23.4). The main abnormalities were: right axis deviation in 5.4% (95% CI 3.5 to 7.7) and left ventricular hypertrophy by voltage criteria in 3.5% (95% CI 2.0 to 5.5). ECG abnormalities were mainly on the left side of the heart for Mustang participants (Tibetan origin) and on the right side for Humla participants (Indo-Aryans). There was a moderate association between the probability of abnormal (or borderline abnormal) ECG and altitude when adjusted for potential confounding variables in a multivariate logistic model; with an OR for association per 1000 m elevation of altitude of 2.83 (95% CI 1.07 to 7.45), p=0.03. Conclusions Electrocardiographic evidence suggests that although high-altitude populations do not have a high prevalence of CHD, abnormal ECG findings increase by altitude and risk pattern varies by ethnicity. PMID:28243317

  6. Alaska High Altitude Photography Program

    NASA Technical Reports Server (NTRS)

    Petersen, Earl V.; Knutson, Martin A.; Ekstrand, Robert E.

    1986-01-01

    In 1978, the Alaska High Altitude Photography Program was initiated to obtain simultaneous black and white and color IR aerial photography of Alaska. Dual RC-10 and Zeiss camera systems were used for this program on NASA's U-2 and WB-57F, respectively. Data collection, handling, and distribution are discussed as well as general applications and the current status.

  7. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Wilson, Megan J.; Lopez, Miriam; Yamashiro, Henry; Tellez, Wilma; Rodriguez, Armando; Bigham, Abigail W.; Shriver, Mark D.; Rodriguez, Carmelo; Vargas, Enrique; Moore, Lorna G.

    2009-01-01

    The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100–4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O2 delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O2 delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O2 delivery than European women at high altitude. PMID:19244584

  8. High altitude observations of Birkeland currents

    NASA Technical Reports Server (NTRS)

    Russell, C. T.

    1977-01-01

    Several models of field-aligned currents (Birkeland currents) in the magnetosphere are discussed, and high altitude observations of these currents, carried out with the aid of highly eccentric earth-orbiting spacecraft of the OGO and IMP series, are reviewed. The essential roles of Birkeland currents are identified: they relieve charge imbalances, transmit stresses, and lead to particle acceleration anomalous resistivity.

  9. Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells.

    PubMed

    Sandbichler, Adolf M; Jansen, Bianca; Peer, Bettina A; Paulitsch, Monika; Pelster, Bernd; Egg, Margit

    2018-01-01

    Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly

  10. High-altitude reconnaissance aircraft

    NASA Technical Reports Server (NTRS)

    Yazdi, Renee Anna

    1991-01-01

    At the equator the ozone layer ranges from 65,000 to 130,000+ ft, which is beyond the capabilities of the ER-2, NASA's current high-altitude reconnaissance aircraft. This project is geared to designing an aircraft that can study the ozone layer. The aircraft must be able to satisfy four mission profiles. The first is a polar mission that ranges from Chile to the South Pole and back to Chile, a total range of 6000 n.m. at 100,000 ft with a 2500-lb payload. The second mission is also a polar mission with a decreased altitude and an increased payload. For the third mission, the aircraft will take off at NASA Ames, cruise at 100,000 ft, and land in Chile. The final mission requires the aircraft to make an excursion to 120,000 ft. All four missions require that a subsonic Mach number be maintained because of constraints imposed by the air sampling equipment. Three aircraft configurations were determined to be the most suitable for meeting the requirements. The performance of each is analyzed to investigate the feasibility of the mission requirements.

  11. High Altitude Towed Glider

    NASA Technical Reports Server (NTRS)

    Colozza, Anthony J.

    1996-01-01

    The concept of using an unmanned towed glider for high altitude scientific research had been previously proposed. This paper examines the feasibility of this concept by determining what impact the various characteristics of the tow line, glider and tow aircraft have on tow line drag. A description of the analysis and computer code used to generate the results is given. The parameters examined were glider altitude, tow aircraft glider separation distance, velocity, tow line drag coefficient and tow line material properties. The results from the analysis show that the tow line drag increases significantly with tow aircraft/glider separation. The drag increased from 940 N (211 lb) with a tow aircraft/glider separation of 3 km to 11,970 N (2691 lb) with a tow aircraft/glider separation of 10 km. The results also show that by varying some of the initial assumptions significant reductions in tow line drag and weight can be obtained. The variables which had the greatest effect on reducing the tow line drag were the decrease in tow aircraft/glider separation distance, the increase in tow line strength and the decrease in glider Mach number.

  12. Severity-dependent influence of isocapnic hypoxia on reaction time is independent of neurovascular coupling.

    PubMed

    Caldwell, Hannah G; Coombs, Geoff B; Tymko, Michael M; Nowak-Flück, Daniela; Ainslie, Philip N

    2018-05-01

    With exposure to acute normobaric hypoxia, global cerebral oxygen delivery is maintained via increases in cerebral blood flow (CBF); therefore, regional and localized changes in oxygen tension may explain neurocognitive impairment. Neurovascular coupling (NVC) is the close temporal and regional relationship of CBF to changes in neural activity and may aid in explaining the localized CBF response with cognitive activation. High-altitude related cognitive impairment is likely affected by hypocapnic cerebral vasoconstriction that may influence regional CBF regulation independent of hypoxia. We assessed neurocognition and NVC following 30 min of acute exposure to isocapnic hypoxia (decreased partial pressure of end-tidal oxygen; P ET O 2 ) during moderate hypoxia (MOD HX; 55 mm Hg P ET O 2 ), and severe hypoxia (SEV HX; 45 mm Hg P ET O 2 ) in 10 healthy individuals (25.5 ± 3.3 yrs). Transcranial Doppler ultrasound was used to assess mean posterior and middle cerebral blood velocity (PCAv and MCAv, respectively) and neurocognitive performance was assessed via validated computerized tests. The main finding was that reaction time (i.e., kinesthetic and visual-motor ability via Stroop test) was selectively impaired in SEV HX (-4.6 ± 5.2%, P = 0.04), but not MOD HX, while complex cognitive performance (e.g., psychomotor speed, cognitive flexibility, processing speed, executive function, and motor speed) was unaffected with hypoxia (P > 0.05). Additionally, severity of hypoxia had no effect on NVC (PCAv CON vs. SEV HX relative peak response 13.7 ± 6.4% vs. 16.2 ± 11.5%, P = 0.71, respectively). In summary, severe isocapnic hypoxia impaired reaction time, but not complex cognitive performance or NVC. These findings have implications for recreational and military personnel who may experience acute hypoxia. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Mild Normobaric Hypoxia Exposure for Human-Autonomy System Testing

    NASA Technical Reports Server (NTRS)

    Stephens, Chad L.; Kennedy, Kellie D.; Crook, Brenda L.; Williams, Ralph A.; Schutte, Paul

    2017-01-01

    An experiment investigated the impact of normobaric hypoxia induction on aircraft pilot performance to specifically evaluate the use of hypoxia as a method to induce mild cognitive impairment to explore human-autonomous systems integration opportunities. Results of this exploratory study show that the effect of 15,000 feet simulated altitude did not induce cognitive deficits as indicated by performance on written, computer-based, or simulated flight tasks. However, the subjective data demonstrated increased effort by the human test subject pilots to maintain equivalent performance in a flight simulation task. This study represents current research intended to add to the current knowledge of performance decrement and pilot workload assessment to improve automation support and increase aviation safety.

  14. Is decision making in hypoxia affected by pre-acclimatisation? A randomized controlled trial.

    PubMed

    Niedermeier, Martin; Weisleitner, Andreas; Lamm, Claus; Ledochowski, Larissa; Frühauf, Anika; Wille, Maria; Burtscher, Martin; Kopp, Martin

    2017-05-01

    Decision making is impaired in hypoxic environments, which may have serious or even lethal consequences for mountaineers. An acclimatisation period prior to high altitude exposures may help to overcome adverse effects of hypoxia. Thus, we investigated possible effects of short-term pre-acclimatisation on decision making in hypoxia. In a randomized controlled study design, 52 healthy participants were allocated to a hypoxia group (HG: short-term pre-acclimatisation by the use of intermittent hypoxia 7×1h at F i O 2 =12.6%, equivalent to 4500m) or a control group (CG: sham pre-acclimatisation 7×1h at F i O 2 =20.9%, equivalent to 600m). The number of risky decisions was assessed using the Game of Dice Task at four time points during a 12-hours stay in hypoxia (F i O 2 =12.6%). 42 (HG: 27, CG: 25) participants completed the study. The number of risky decisions was significantly (p=0.048 as determined by 4×2 ANCOVA) reduced in the hypoxia group compared to the control group, partial η 2 =0.11, when the age-effect on decision making was controlled. Self-reported positive affective valence prior to decision making was negatively related to the number of risky decisions, r<-0.38. Short-term pre-acclimatisation might influence decision making in hypoxia in a positive way and might be considered as a risk-reducing preparation method prior to exposures to hypoxic environments. Positive affective states seem to have a medium-sized protective effect against risky decision making. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Positive Association of D Allele of ACE Gene With High Altitude Pulmonary Edema in Indian Population.

    PubMed

    Bhagi, Shuchi; Srivastava, Swati; Tomar, Arvind; Bala Singh, Shashi; Sarkar, Soma

    2015-06-01

    High altitude pulmonary edema (HAPE) is a potentially fatal high altitude illness occurring as a result of hypobaric hypoxia with an unknown underlying genetic mechanism. Recent studies have shown a possible association between HAPE and polymorphisms in genes of the renin-angiotensin-aldosterone system (RAAS), which play a key role in sensitivity of an individual toward HAPE. For the present investigation, study groups consisted of HAPE patients (HAPE) and acclimatized control subjects (rCON). Four single-nucleotide polymorphisms (SNPs) were genotyped using restriction fragment length polymorphism (RFLP) analysis in genes of the RAAS pathway, specifically, renin (REN) C(-4063)T (rs41317140) and RENi8-83 (rs2368564), angiotensin (AGT) M(235)T (rs699), and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) (rs1799752). Only the I/D polymorphism of the ACE gene showed a significant difference between the HAPE and rCON groups. The frequency of the D allele was found to be significantly higher in the HAPE group. Arterial oxygen saturation levels were significantly lower in the HAPE group compared with the rCON group and also decreased in the I/D and D/D genotypes compared with the I/I genotype in these groups. The other polymorphisms occurring in the REN and AGT genes were not significantly different between the 2 groups. These findings demonstrate a possible association of the I/D polymorphism of the ACE gene with the development of HAPE, with D/D being the at-risk genotype. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  16. Functional characterization and expression analysis of myoglobin in high-altitude lizard Phrynocephalus erythrurus.

    PubMed

    Xin, Ying; Tang, Xiaolong; Wang, Huihui; Lu, Songsong; Wang, Yan; Zhang, Yang; Chen, Qiang

    2015-10-01

    Myoglobin (Mb) is a monomeric hemoprotein which plays an important role in oxygen storage and transport in cardiac and skeletal muscle under hypoxia. The red tail toad-headed lizard Phrynocephalus erythrurus (Lacertilia: Agamidae), which inhabits at an elevation of 4500-5300 m on the Qinghai-Tibetan plateau, is known to be the highest living lizard in the world. To investigate the characters of myoglobin of this unique species, another low altitude lizard Phrynocephalus przewalskii (Lacertilia: Agamidae) was selected as a reference. The open reading frame (ORF) of myoglobin in two lizards was 465 bp which encodes a polypeptide of 154 amino acids with different theoretical molecular weight and isoelectric point. The amino acid substitutions of myoglobin between two species were found at Thr13Ile, Lys87Thr and His118Asn. Homology modeling results indicated that P. erythrurus myoglobin has a greater heme pocket, which may be more favorable to oxygen binding and unloading. On the other hand, the mRNA levels of myoglobin in both cardiac and skeletal muscle in P. erythrurus were significantly larger than those in low altitude P. przewalskii. At protein level, myoglobin concentration in skeletal muscle in P. erythrurus was notably increased, but no significant difference was observed in cardiac muscle. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric Hypoxia Exposure in a Rat Model: Role of Oxidative Stress

    PubMed Central

    Aguilar, Miguel; Rodríguez, Jorge; Carrasco-Pozo, Catalina; Cañas, Daniel; García-Herrera, Claudio; Herrera, Emilio A.

    2018-01-01

    More than 140 million people live and works (in a chronic or intermittent form) above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 55,000 persons work in high altitude shifts, where stays at lowlands and interspersed with working stays at highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders, due to an increase in free radical formation and a decrease in antioxidant capacity. However, in animal models, intermittent hypoxia (IH) induce preconditioning, like responses and cardioprotection. Here, we aimed to describe in a rat model the responses on cardiac and vascular function to 4 cycles of intermittent hypobaric hypoxia (IHH). Twelve adult Wistar rats were randomly divided into two equal groups, a four-cycle of IHH, and a normobaric hypoxic control. Intermittent hypoxia was induced in a hypobaric chamber in four continuous cycles (1 cycle = 4 days hypoxia + 4 days normoxia), reaching a barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of the first and fourth cycle, cardiac structural, and functional variables were determined by echocardiography. Thereafter, ex vivo vascular function and biomechanical properties were determined in femoral arteries by wire myography. We further measured cardiac oxidative stress biomarkers (4-Hydroxy-nonenal, HNE; nytrotirosine, NT), reactive oxygen species (ROS) sources (NADPH and mitochondrial), and antioxidant enzymes activity (catalase, CAT; glutathione peroxidase, GPx, and superoxide dismutase, SOD). Our results show a higher ejection and shortening fraction of the left ventricle function by the end of the 4th cycle. Further, femoral vessels showed an improvement of vasodilator capacity and diminished stiffening. Cardiac tissue presented a higher expression of antioxidant enzymes and mitochondrial ROS formation in IHH, as compared with normobaric hypoxic controls. IHH exposure

  18. Reduced oxygen at high altitude limits maximum size.

    PubMed

    Peck, L S; Chapelle, G

    2003-11-07

    The trend towards large size in marine animals with latitude, and the existence of giant marine species in polar regions have long been recognized, but remained enigmatic until a recent study showed it to be an effect of increased oxygen availability in sea water of a low temperature. The effect was apparent in data from 12 sites worldwide because of variations in water oxygen content controlled by differences in temperature and salinity. Another major physical factor affecting oxygen content in aquatic environments is reduced pressure at high altitude. Suitable data from high-altitude sites are very scarce. However, an exceptionally rich crustacean collection, which remains largely undescribed, was obtained by the British 1937 expedition from Lake Titicaca on the border between Peru and Bolivia in the Andes at an altitude of 3809 m. We show that in Lake Titicaca the maximum length of amphipods is 2-4 times smaller than other low-salinity sites (Caspian Sea and Lake Baikal).

  19. Reduced oxygen at high altitude limits maximum size.

    PubMed Central

    Peck, L S; Chapelle, G

    2003-01-01

    The trend towards large size in marine animals with latitude, and the existence of giant marine species in polar regions have long been recognized, but remained enigmatic until a recent study showed it to be an effect of increased oxygen availability in sea water of a low temperature. The effect was apparent in data from 12 sites worldwide because of variations in water oxygen content controlled by differences in temperature and salinity. Another major physical factor affecting oxygen content in aquatic environments is reduced pressure at high altitude. Suitable data from high-altitude sites are very scarce. However, an exceptionally rich crustacean collection, which remains largely undescribed, was obtained by the British 1937 expedition from Lake Titicaca on the border between Peru and Bolivia in the Andes at an altitude of 3809 m. We show that in Lake Titicaca the maximum length of amphipods is 2-4 times smaller than other low-salinity sites (Caspian Sea and Lake Baikal). PMID:14667371

  20. Extreme Terrestrial Environments: Life in Thermal Stress and Hypoxia. A Narrative Review.

    PubMed

    Burtscher, Martin; Gatterer, Hannes; Burtscher, Johannes; Mairbäurl, Heimo

    2018-01-01

    Living, working and exercising in extreme terrestrial environments are challenging tasks even for healthy humans of the modern new age. The issue is not just survival in remote environments but rather the achievement of optimal performance in everyday life, occupation, and sports. Various adaptive biological processes can take place to cope with the specific stressors of extreme terrestrial environments like cold, heat, and hypoxia (high altitude). This review provides an overview of the physiological and morphological aspects of adaptive responses in these environmental stressors at the level of organs, tissues, and cells. Furthermore, adjustments existing in native people living in such extreme conditions on the earth as well as acute adaptive responses in newcomers are discussed. These insights into general adaptability of humans are complemented by outcomes of specific acclimatization/acclimation studies adding important information how to cope appropriately with extreme environmental temperatures and hypoxia.

  1. Extreme Terrestrial Environments: Life in Thermal Stress and Hypoxia. A Narrative Review

    PubMed Central

    Burtscher, Martin; Gatterer, Hannes; Burtscher, Johannes; Mairbäurl, Heimo

    2018-01-01

    Living, working and exercising in extreme terrestrial environments are challenging tasks even for healthy humans of the modern new age. The issue is not just survival in remote environments but rather the achievement of optimal performance in everyday life, occupation, and sports. Various adaptive biological processes can take place to cope with the specific stressors of extreme terrestrial environments like cold, heat, and hypoxia (high altitude). This review provides an overview of the physiological and morphological aspects of adaptive responses in these environmental stressors at the level of organs, tissues, and cells. Furthermore, adjustments existing in native people living in such extreme conditions on the earth as well as acute adaptive responses in newcomers are discussed. These insights into general adaptability of humans are complemented by outcomes of specific acclimatization/acclimation studies adding important information how to cope appropriately with extreme environmental temperatures and hypoxia. PMID:29867589

  2. Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia

    PubMed Central

    2010-01-01

    Background The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses. Methods Design Observational cohort study of progressive incremental exposure to EHH. Setting University human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m. Participants 198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest. Main outcome measures Exercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry. Results Of 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood

  3. Importance of functional ingredients in yak milk-derived food on health of Tibetan nomads living under high-altitude stress: a review.

    PubMed

    Guo, Xusheng; Long, Ruijun; Kreuzer, Michael; Ding, Luming; Shang, Zhanhuan; Zhang, Ying; Yang, Yang; Cui, Guangxin

    2014-01-01

    Tibetan nomads have lived since ancient times in the unique and harsh environment of the Qinghai-Tibetan Plateau with average altitudes over 4000 m. These people have been able to live and multiply healthily over numerous generations under the extreme stress of high-altitude environment, including cold, hypoxia, and strong ultraviolet radiation, and with a simple diet devoid of vegetables and fruits for most of the year. Their survival depends heavily on yak milk, and its products comprise the main portion of their daily diet. In this review, yak milk and its derived products are examined in detail and compared with milk from other ruminant species. Yak milk products seem to be particularly rich in functional and bioactive components, which may play a role in maintaining the health status of Tibetan nomads. This includes particular profiles of amino acids and fatty acids, and high levels of antioxidant vitamins, specific enzymes, and bacteria with probiotic activity (yoghurt is the main food). Based on that, it is proposed that the Tibetan nomads have developed a nutritional mechanism adapted to cope with the specific challenges posed by the environment of the world's highest plateau. Systematic studies are required to demonstrate this in a more mechanistic way.

  4. Long-Term Health Outcomes in High-Altitude Pulmonary Hypertension

    PubMed Central

    Abbott, Cheryl; Meadows, Christina A.; Roach, Robert C.; Honigman, Benjamin; Bull, Todd M.

    2017-01-01

    Abstract Robinson, Jeffrey C., Cheryl Abbott, Christina A. Meadows, Robert C. Roach, Benjamin Honigman, and Todd M. Bull. Long-term health outcomes in high-altitude pulmonary hypertension. High Alt Med Biol. 18:61–66, 2017. Background: High-altitude pulmonary hypertension (HAPH) is one of several known comorbidities that effect populations living at high altitude, but there have been no studies looking at long-term health consequences of HAPH. We aimed to determine whether HAPH during adolescence predisposes to significant pulmonary hypertension (PH) later in life, as well as identify how altitude exposure and HAPH correlate with functional class and medical comorbidities. Methods: We utilized a previously published cohort of 28 adolescents from Leadville, Colorado, that underwent right heart catheterization at 10,150 ft (3094 m) in 1962, with many demonstrating PH as defined by resting mean pulmonary arterial pressure ≥25 mmHg. We located participants of the original study and had living subjects complete demographic and health surveys to assess for the presence of PH and other medical comorbidities, along with current functional status. Results: Seventy-five percent of the individuals who participated in the original study were located. Those with HAPH in the past were more prone to have exertional limitation corresponding to WHO functional class >1. Fifty-five years following the original study, we found no significant differences in prevalence of medical comorbidities, including PH, among those with and without HAPH in their youth. Conclusions: Surveyed individuals did not report significant PH, but those with HAPH in their youth were more likely to report functional limitation. With a significant worldwide population living at moderate and high altitudes, further study of long-term health consequences is warranted. PMID:28061144

  5. Measuring arterial oxygenation in a high altitude field environment: comparing portable pulse oximetry with blood gas analysis.

    PubMed

    Ross, Elliot M; Matteucci, Michael J; Shepherd, Matthew; Barker, Matthew; Orr, Lance

    2013-06-01

    High altitude environments present unique medical treatment challenges. Medical providers often use small portable pulse oximetry devices to help guide their clinical decision making. A significant body of high altitude research is based on the use of these devices to monitor hypoxia, yet there is a paucity of evidence that these devices are accurate in these environments. We studied whether these devices perform accurately and reliably under true mountain conditions. Healthy unacclimatized active-duty military volunteers participating in mountain warfare training at 2100 m (6900 feet) above sea level were evaluated with several different pulse oximetry devices while in a cold weather, high altitude field environment and then had arterial blood gases (ABG) drawn using an i-STAT for comparison. The pulse oximeter readings were compared with the gold standard ABG readings. A total of 49 individuals completed the study. There was no statistically significant difference between any of the devices and the gold standard of ABG. The best performing device was the PalmSAT (PS) 8000SM finger probe with a mean difference of 2.17% and SD of 2.56 (95% CI, 1.42% to 2.92%). In decreasing order of performance were the PS 8000AA finger probe (mean ± SD, 2.54% ± 2.68%; 95% CI, 1.76% to 3.32%), the PS 8000Q ear probe (2.47% ± 4.36%; 95% CI, 1.21% to 3.75%), the Nonin Onyx 9500 (3.29% ± 3.12%; 95% CI, 2.39% to 4.20%), and finally the PS 8000R forehead reflectance sensor (5.15% ± 2.97%; 95% CI, 4.28% to 6.01%). Based on the results of this study, results of the newer portable pulse oximeters appear to be closely correlated to that of the ABG measurements when tested in true mountain conditions. Copyright © 2013 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  6. Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia

    PubMed Central

    Petousi, Nayia; Croft, Quentin P. P.; Cavalleri, Gianpiero L.; Cheng, Hung-Yuan; Formenti, Federico; Ishida, Koji; Lunn, Daniel; McCormack, Mark; Shianna, Kevin V.; Talbot, Nick P.; Ratcliffe, Peter J.

    2013-01-01

    Tibetan natives have lived on the Tibetan plateau (altitude ∼4,000 m) for at least 25,000 years, and as such they are adapted to life and reproduction in a hypoxic environment. Recent studies have identified two genetic loci, EGLN1 and EPAS1, that have undergone natural selection in Tibetans, and further demonstrated an association of EGLN1/EPAS1 genotype with hemoglobin concentration. Both genes encode major components of the hypoxia-inducible factor (HIF) transcriptional pathway, which coordinates an organism's response to hypoxia. Patients living at sea level with genetic disease of the HIF pathway have characteristic phenotypes at both the integrative-physiology and cellular level. We sought to test the hypothesis that natural selection to hypoxia within Tibetans results in related phenotypic differences. We compared Tibetans living at sea level with Han Chinese, who are Tibetans' most closely related major ethnic group. We found that Tibetans had a lower hemoglobin concentration, a higher pulmonary ventilation relative to metabolism, and blunted pulmonary vascular responses to both acute (minutes) and sustained (8 h) hypoxia. At the cellular level, the relative expression and hypoxic induction of HIF-regulated genes were significantly lower in peripheral blood lymphocytes from Tibetans compared with Han Chinese. Within the Tibetans, we found a significant correlation between both EPAS1 and EGLN1 genotype and the induction of erythropoietin by hypoxia. In conclusion, this study provides further evidence that Tibetans respond less vigorously to hypoxic challenge. This is evident at sea level and, at least in part, appears to arise from a hyporesponsive HIF transcriptional system. PMID:24030663

  7. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats

    PubMed Central

    Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

    2016-01-01

    Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID:26901349

  8. AltitudeOmics: exercise-induced supraspinal fatigue is attenuated in healthy humans after acclimatization to high altitude.

    PubMed

    Goodall, S; Twomey, R; Amann, M; Ross, E Z; Lovering, A T; Romer, L M; Subudhi, A W; Roach, R C

    2014-04-01

    We asked whether acclimatization to chronic hypoxia (CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia (AH). Seven recreationally active participants performed identical bouts of constant-load cycling (131 ± 39 W, 10.1 ± 1.4 min) on three occasions: (i) in normoxia (N, PI O2 , 147.1 mmHg); (ii) in AH (FI O2 , 0.105; PI O2 , 73.8 mmHg); and (iii) after 14 days in CH (5260 m; PI O2 , 75.7 mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared-spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch responses to femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and corticospinal function. In AH, prefrontal oxygenation declined at rest (Δ7 ± 5%) and end-exercise (Δ26 ± 13%) (P < 0.01); the degree of deoxygenation in AH was greater than N and CH (P < 0.05). The cerebral O2 delivery index (MCAV × Ca O2 ) was 19 ± 14% lower during the final minute of exercise in AH compared to N (P = 0.013) and 20 ± 12% lower compared to CH (P = 0.040). Maximum voluntary and potentiated twitch force were decreased below baseline after exercise in AH and CH, but not N. Cortical voluntary activation decreased below baseline after exercise in AH (Δ11%, P = 0.014), but not CH (Δ6%, P = 0.174) or N (Δ4%, P = 0.298). A twofold greater increase in motor-evoked potential amplitude was evident after exercise in CH compared to AH and N. These data indicate that exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days of acclimatization to altitude. The reduced development of supraspinal fatigue in CH may have been attributable to increased corticospinal excitability, consequent to an increased cerebral O2 delivery. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  9. The Effects of Altitude Training on Erythropoietic Response and Hematological Variables in Adult Athletes: A Narrative Review

    PubMed Central

    Płoszczyca, Kamila; Langfort, Józef; Czuba, Miłosz

    2018-01-01

    Background: One of the goals of altitude training is to increase blood oxygen-carrying capacity in order to improve sea-level endurance performance in athletes. The elevated erythropoietin (EPO) production in hypoxia is a key factor in the achievement of enhanced hematological variables. The level of the EPO increase and acceleration of erythropoiesis depend on the duration of exposure and degree of hypoxia. Furthermore, many other factors may affect the hematological response to altitude training. Aim: The purpose of this narrative review was to: (1) analyze the kinetics of EPO and hematological variables during and after altitude training; (2) summarize the current state of knowledge about the possible causes of individual or cohort differences in EPO and hematological response to altitude training; (3) formulate practical guidelines for athletes to improve the efficiency of altitude training. Methods: A narrative review was performed following an electronic search of the databases PubMed/MEDLINE and SPORTDiscus via EBSCO for all English-language articles published between 1997 and 2017. Results: Complete unification of results from studies on EPO kinetics was difficult due to different time and frequency of blood sampling by different researchers during and after altitude training, but the data presented in the reviewed literature allowed us to detect certain trends. The results of the reviewed studies were divergent and indicated either increase or no change of hematological variables following altitude training. Factors that may affect the hematological response to altitude training include hypoxic dose, training content, training background of athletes, and/or individual variability of EPO production. Conclusions: Despite the potential benefits arising from altitude training, its effectiveness in improving hematological variables is still debatable. Further research and better understanding of factors influencing the response to altitude, as well as factors

  10. Altitude, gun ownership, rural areas, and suicide.

    PubMed

    Kim, Namkug; Mickelson, Jennie B; Brenner, Barry E; Haws, Charlotte A; Yurgelun-Todd, Deborah A; Renshaw, Perry F

    2011-01-01

    The authors recently observed a correlation between state altitude and suicide rate in the United States, which could be explained by higher rates of gun ownership and lower population density in the intermountain West. The present study evaluated the relationship between mean county and state altitude in the United States and total age-adjusted suicide rates, firearm-related suicide rates, and non-firearm-related suicide rates. The authors hypothesized that altitude would be significantly associated with suicide rate. Elevation data were calculated with an approximate spatial resolution of 0.5 km, using zonal statistics on data sets compiled from the National Geospatial-Intelligence Agency and the National Aeronautics and Space Administration. Suicide and population density data were obtained through the Centers for Disease Control and Prevention (CDC) WONDER database. Gun ownership data were obtained through the CDC's Behavioral Risk Factor Surveillance System. A significant positive correlation was observed between age-adjusted suicide rate and county elevation (r=0.51). Firearm (r=0.41) and non-firearm suicide rates (r=0.32) were also positively correlated with mean county elevation. When altitude, gun ownership, and population density are considered as predictor variables for suicide rates on a state basis, altitude appears to be a significant independent risk factor. This association may be related to the effects of metabolic stress associated with mild hypoxia in individuals with mood disorders.

  11. High altitude, prolonged exercise, and the athlete biological passport.

    PubMed

    Schumacher, Yorck O; Garvican, Laura A; Christian, Ryan; Lobigs, Louisa M; Qi, Jiliang; Fan, Rongyun; He, Yingying; Wang, Hailing; Gore, Christopher J; Ma, Fuhai

    2015-01-01

    The Athlete Biological Passport (ABP) detects blood doping in athletes through longitudinal monitoring of erythropoietic markers. Mathematical algorithms are used to define individual reference ranges for these markers for each athlete. It is unclear if altitude and exercise can affect the variables included in these calculations in a way that the changes might be mistaken for blood manipulation. The aim of this study was to investigate the influence of the simultaneous strenuous exercise and low to high altitude exposure on the calculation algorithms of the ABP. 14 sea level (SL) and 11 altitude native (ALT) highly trained athletes participated in a 14-day cycling stage race taking place at an average altitude of 2496 m above sea level (min. 1014 m, max. 4120 m), race distances ranged between 96 and 227 km per day. ABP blood measures were taken on days -1,3,6,10,14 (SL) and -1,9,15 (ALT) of the race. Four results from three samples of two different SL athletes exceeded the individual limits at the 99% specificity threshold and one value at 99.9%. In ALT, three results from three samples of three different athletes were beyond the individual limits at 99%, one at 99.9%. The variations could be explained by the expected physiological reaction to exercise and altitude. In summary, the abnormalities observed in the haematological ABP´s of well-trained athletes during extensive exercise at altitude are limited and in line with expected physiological changes. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Chronic Hypoxia Suppresses Pregnancy-Induced Upregulation of Large-Conductance Ca2+-Activated K+ Channel Activity in Uterine Arteries

    PubMed Central

    Hu, Xiang-Qun; Xiao, Daliao; Zhu, Ronghui; Huang, Xiaohui; Yang, Shumei; Wilson, Sean M.; Zhang, Lubo

    2013-01-01

    Our previous study demonstrated that increased Ca2+-activated K+ (BKCa) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BKCa channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BKCa channel activity and suppressed BKCa channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BKCa channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BKCa channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BKCa channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BKCa channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BKCa channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia. PMID:22665123

  13. Size restricted silymarin suspension evokes integrated adaptive response against acute hypoxia exposure in rat lung.

    PubMed

    Paul, Subhojit; Arya, Aditya; Gangwar, Anamika; Bhargava, Kalpana; Ahmad, Yasmin

    2016-07-01

    Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous solubility, are two main causes that have dampened the clinical applicability and scope of this preparation. We took these two challenges and suggested an unexplored application of silymarin. Apart from liver, two of the most susceptible vital organs at the highest risk of oxidative stress are brain and lung, especially during reduced oxygen saturation (hypoxia) at anatomical level. Hypoxia causes excess generation of radicals primarily in the lungs as it is the first organ at the interphase of atmosphere and organism making it the most prone and vulnerable to oxidative stress and the first responder against hypobaric hypoxia. As our first objective, we improved the silymarin formulation by restricting its size to the lower threshold and then successfully tested the prophylactic and therapeutic action in rat lung challenged with simulated hypobaric hypoxia. After dose optimization, we observed that 50mg/kg BW silymarin as size restricted and homogenous aqueous suspension successfully minimized the reactive oxygen species and augmented the antioxidant defense by significant upregulation of catalase and superoxide dismutase and reduced glutathione. Moreover, the well-established hypoxia markers and proteins related to hypoxia adaptability, hif1a and VEGF were differentially regulated conferring significant reduction in the inflammation caused by hypobaric hypoxia. We therefore report,the unexplored potential benefits of silymarin for preventing high altitude associated pathophysiology further paving its road to clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Circulatory adaptation to long-term high altitude exposure in Aymaras and Caucasians.

    PubMed

    Stuber, Thomas; Scherrer, Urs

    2010-01-01

    About 30 million people live above 2500 m in the Andean Mountains of South America. Among them are 5.5 million Aymaras, an ethnic group with its own language, living on the altiplano of Bolivia, Peru, and northern Chile at altitudes of up to 4400 m. In this high altitude region traces of human population go back for more than 2000 years with constant evolutionary pressure on its residents for genetic adaptation to high altitude. Aymaras as the assumed direct descendents of the ancient cultures living in this region were the focus of much research interest during the last decades and several distinctive adaptation patterns to life at high altitude have been described in this ethnic group. The aim of this article was to review the physiology and pathophysiology of circulatory adaptation and maladaptation to longtime altitude exposure in Aymaras and Caucasians.

  15. Evolution of nonspectral rhodopsin function at high altitudes.

    PubMed

    Castiglione, Gianni M; Hauser, Frances E; Liao, Brian S; Lujan, Nathan K; Van Nynatten, Alexander; Morrow, James M; Schott, Ryan K; Bhattacharyya, Nihar; Dungan, Sarah Z; Chang, Belinda S W

    2017-07-11

    High-altitude environments present a range of biochemical and physiological challenges for organisms through decreases in oxygen, pressure, and temperature relative to lowland habitats. Protein-level adaptations to hypoxic high-altitude conditions have been identified in multiple terrestrial endotherms; however, comparable adaptations in aquatic ectotherms, such as fishes, have not been as extensively characterized. In enzyme proteins, cold adaptation is attained through functional trade-offs between stability and activity, often mediated by substitutions outside the active site. Little is known whether signaling proteins [e.g., G protein-coupled receptors (GPCRs)] exhibit natural variation in response to cold temperatures. Rhodopsin (RH1), the temperature-sensitive visual pigment mediating dim-light vision, offers an opportunity to enhance our understanding of thermal adaptation in a model GPCR. Here, we investigate the evolution of rhodopsin function in an Andean mountain catfish system spanning a range of elevations. Using molecular evolutionary analyses and site-directed mutagenesis experiments, we provide evidence for cold adaptation in RH1. We find that unique amino acid substitutions occur at sites under positive selection in high-altitude catfishes, located at opposite ends of the RH1 intramolecular hydrogen-bonding network. Natural high-altitude variants introduced into these sites via mutagenesis have limited effects on spectral tuning, yet decrease the stability of dark-state and light-activated rhodopsin, accelerating the decay of ligand-bound forms. As found in cold-adapted enzymes, this phenotype likely compensates for a cold-induced decrease in kinetic rates-properties of rhodopsin that mediate rod sensitivity and visual performance. Our results support a role for natural variation in enhancing the performance of GPCRs in response to cold temperatures.

  16. Reference values for pulse oximetry at high altitude

    PubMed Central

    Gamponia, M; Babaali, H; Yugar, F; Gilman, R

    1998-01-01

    OBJECTIVE—To determine reference values for oxygen saturation (SaO2) in healthy children younger than 5 years living at high altitude.
DESIGN—One hundred and sixty eight children were examined for SaO2 at 4018 m during well child visits. Physiological state was also noted during the examination.
RESULTS—The mean SaO2 was 87.3% (95% confidence intervals (CI) 86.7%, 87.9%) with a median value of 87.7%. A significant difference was observed in SaO2 between children younger than 1 year compared with older children, although the difference was no longer demonstrable when sleeping children were excluded.
CONCLUSIONS—This study has provided a reference range of SaO2 values for healthy children under 5 years old so that pulse oximetry may be used as an adjunct in diagnosing acute respiratory infections. Younger children were also shown to have a lower mean SaO2 than older children living at high altitude, which suggests physiological adaptation to high altitude over time. In addition, sleep had a lowering effect on SaO2, although the clinical importance of this remains undetermined.

 PMID:9659095

  17. Adaption to High Altitude: An Evaluation of the Storage Quality of Suspended Red Blood Cells Prepared from the Whole Blood of Tibetan Plateau Migrants

    PubMed Central

    Wang, Hong; Li, Xiaojuan; He, Zeng; Gangla, Meiduo; Zhang, Jingdan; Han, Dingding; Liu, Jiaxin

    2015-01-01

    Hypoxia has been reported to cause the significant enhancement of hemoglobin (Hb) and hematocrit (Hct), which stabilizes at relatively high levels after an individual ascends to a high altitude. However, the quality of the suspended red blood cells (SRBCs) obtained from individuals at high altitudes such as Tibetan plateau migrants after storage has not been studied. In this study, we compared the storage quality of SRBCs prepared from Tibetan plateau and Deyang lowland populations by adding a normal volume of mannitol-adenine-phosphate (MAP), which is a common additive solution used in blood storage in Asian countries. The storage cell characteristics were examined on days1, 7, 14 and 35.We found higher Hct and Hb levels and viscosity in the high altitude samples. The metabolic rates, including those for electrolytes and lactate, were higher in plateau SRBCs than in lowland SRBCs; these findings were consistent with the higher osmotic fragility and hemolysis of plateau SRBCs throughout the entire storage period. In addition, the reduction rates of 2,3-diphosphoglycerate (2,3-DPG) and oxygen tension to attain 50% oxygen saturation of Hb (P50) in plateau SRBCs were higher than those in lowland SRBCs, and the oxygen delivering capacity in plateau SRBCs was weaker than that in lowland SRBCs. We concluded that the storage quality of plateau SRBCs was inferior to that of lowland SRBCs when using the same concentration of MAP. We suggested that the optimal formula, including the MAP concentration or even a new additive solution, to store the plateau SRBCs must be assessed and regulated. PMID:26637115

  18. The radiation protection problems of high altitude and space flight

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fry, R.J.M.

    1993-04-01

    This paper considers the radiation environment in aircraft at high altitudes and spacecraft in low earth orbit and in deep space and the factors that influence the dose equivalents. Altitude, latitude and solar cycle are the major influences for flights below the radiation belts. In deep space, solar cycle and the occurrence of solar particle events are the factors of influence. The major radiation effects of concern are cancer and infertility in males. In high altitude aircraft the radiation consists mainly of protons and neutrons, with neutrons contributing about half the equivalent dose. The average dose rate at altitudes ofmore » transcontinental flights that approach the polar regions are greater by a factor of about 2.5 than on routes at low latitudes. Current estimates of does to air crews suggest they are well within the ICRP (1990) recommended dose limits for radiation workers.« less

  19. Adaptation of the Long-Lived Monocarpic Perennial Saxifraga longifolia to High Altitude.

    PubMed

    Munné-Bosch, Sergi; Cotado, Alba; Morales, Melanie; Fleta-Soriano, Eva; Villellas, Jesús; Garcia, Maria B

    2016-10-01

    Global change is exerting a major effect on plant communities, altering their potential capacity for adaptation. Here, we aimed at unveiling mechanisms of adaptation to high altitude in an endemic long-lived monocarpic, Saxifraga longifolia, by combining demographic and physiological approaches. Plants from three altitudes (570, 1100, and 2100 m above sea level [a.s.l.]) were investigated in terms of leaf water and pigment contents, and activation of stress defense mechanisms. The influence of plant size on physiological performance and mortality was also investigated. Levels of photoprotective molecules (α-tocopherol, carotenoids, and anthocyanins) increased in response to high altitude (1100 relative to 570 m a.s.l.), which was paralleled by reduced soil and leaf water contents and increased ABA levels. The more demanding effect of high altitude on photoprotection was, however, partly abolished at very high altitudes (2100 m a.s.l.) due to improved soil water contents, with the exception of α-tocopherol accumulation. α-Tocopherol levels increased progressively at increasing altitudes, which paralleled with reductions in lipid peroxidation, thus suggesting plants from the highest altitude effectively withstood high light stress. Furthermore, mortality of juveniles was highest at the intermediate population, suggesting that drought stress was the main environmental driver of mortality of juveniles in this rocky plant species. Population structure and vital rates in the high population evidenced lower recruitment and mortality in juveniles, activation of clonal growth, and absence of plant size-dependent mortality. We conclude that, despite S. longifolia has evolved complex mechanisms of adaptation to altitude at the cellular, whole-plant and population levels, drought events may drive increased mortality in the framework of global change. © 2016 American Society of Plant Biologists. All Rights Reserved.

  20. Project ARES 2: High-altitude battery-powered aircraft

    NASA Technical Reports Server (NTRS)

    1991-01-01

    A high-altitude, battery-powered, propeller-driven aircraft was designed and is being built by undergraduate students at California State University, Northridge. The aircraft will fly at an altitude of 104,000 ft at Mach 0.2 (190 ft/sec) and will be instrumented to record flight performance data, including low Reynolds number propeller and airfoil information. This project will demonstrate the feasibility of electric-powered flight in a low-density, low-temperature Earth environment that models the atmosphere of Mars. Data collected will be used to design a Mars aircraft to investigate the surface of Mars prior to manned missions. The instrumented payload and the mission profile for the high-altitude Earth flight were determined. Detailed aerodynamic and structural analyses were performed. Control, tracking, and data recording subsystems were developed. Materials were obtained and fabrication begun. The aircraft has a 32-ft wing span, a wing area of 105 sq ft, is 17.5 ft long, has a 12-in payload bay, and weighs 42 lb. It is composed primarily of lightweight materials, including Mylar, and composite materials, including graphite/epoxy and aramid core honeycomb sandwich. Low-altitude flight testing to check guidance and control systems and to calibrate data-gathering instruments will take place this summer, followed shortly by the 104,000-ft flight.

  1. Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

    PubMed

    Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

    2015-06-15

    Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

  2. From Low Altitude to High Altitude: Assimilating SAMPEX Data in Global Radiation Belt Models by Quantifying Precipitation and Loss

    NASA Astrophysics Data System (ADS)

    Tu, W.; Reeves, G. D.; Cunningham, G.; Selesnick, R. S.; Li, X.; Looper, M. D.

    2012-12-01

    Since its launch in 1992, SAMPEX has been continuously providing measurements of radiation belt electrons at low altitude, which are not only ideal for the direct quantification of the electron precipitation loss in the radiation belt, but also provide data coverage in a critical region for global radiation belt data assimilation models. However, quantitatively combining high-altitude and low-earth-orbit (LEO) measurements on the same L-shell is challenging because LEO measurements typically contain a dynamic mixture of trapped and precipitating populations. Specifically, the electrons measured by SAMPEX can be distinguished as trapped, quasi-trapped (in the drift loss cone), and precipitating (in the bounce loss cone). To simulate the low-altitude electron distribution observed by SAMPEX/PET, a drift-diffusion model has been developed that includes the effects of azimuthal drift and pitch angle diffusion. The simulation provides direct quantification of the rates and variations of electron loss to the atmosphere, a direct input to our Dynamic Radiation Environment Assimilation Model (DREAM) as the electron loss lifetimes. The current DREAM uses data assimilation to combine a 1D radial diffusion model with observational data of radiation belt electrons. In order to implement the mixed electron measurements from SAMPEX into DREAM, we need to map the SAMPEX data from low altitude to high altitudes. To perform the mapping, we will first examine the well-known 'global coherence' of radiation belt electrons by comparing SAMPEX electron fluxes with the energetic electron data from LANL GEO and GPS spacecraft. If the correlation is good, we can directly map the SAMPEX fluxes to high altitudes based on the global coherence; if not, we will use the derived pitch angle distribution from the drift-diffusion model to map up the field and test the mapping by comparing to the high-altitude flux measurements. Then the globally mapped electron fluxes can be assimilated into DREAM

  3. Scientific Approach for Optimising Performance, Health and Safety in High-Altitude Observatories

    NASA Astrophysics Data System (ADS)

    Böcker, Michael; Vogy, Joachim; Nolle-Gösser, Tanja

    2008-09-01

    The ESO coordinated study “Optimising Performance, Health and Safety in High-Altitude Observatories” is based on a psychological approach using a questionnaire for data collection and assessment of high-altitude effects. During 2007 and 2008, data from 28 staff and visitors involved in APEX and ALMA were collected and analysed and the first results of the study are summarised. While there is a lot of information about biomedical changes at high altitude, relatively few studies have focussed on psychological changes, for example with respect to performance of mental tasks, safety consciousness and emotions. Both, biomedical and psychological changes are relevant factors in occupational safety and health. The results of the questionnaire on safety, health and performance issues demonstrate that the working conditions at high altitude are less detrimental than expected.

  4. Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population.

    PubMed

    Calderón-Gerstein, Walter S; López-Peña, Antonio; Macha-Ramírez, Raúl; Bruno-Huamán, Astrid; Espejo-Ramos, Roxana; Vílchez-Bravo, Stephany; Ramírez-Breña, María; Damián-Mucha, Milagros; Matos-Mucha, Adriana

    2017-01-01

    Endothelial function at high altitude has been measured only in populations that are genetically adapted to chronic hypoxia. The objective of this study was to evaluate endothelial dysfunction (ED) in a nongenetically adapted high-altitude population of the Andes mountains, in Huancayo, Peru (3,250 meters above sea level). Participants included 61 patients: 28 cases and 33 controls. The cases were subjects with hypertension, diabetes mellitus, obesity, or a history of stroke or coronary artery disease. Flow-mediated vasodilation (FMD) of the brachial artery was measured in the supine position, at noon, after 5 minutes of resting. The brachial artery was identified above the elbow. Its basal diameter was measured during diastole, and FMD was tested after 5 minutes of forearm ischemia. Intima-media complex in the right carotid artery was also determined. An increase in the artery's baseline diameter <10% indicated a positive test. Endothelium-independent vasodilation was evaluated with sublingual nitrate administration. The intima-media complex in the right carotid artery was also measured. 100% of diabetics had ED; ED was also found in 68.8% of obese individuals, 55% of hypertensive patients, and 46.5% of controls. Age, height, body mass index, and waist diameter were higher in the cases as compared with the controls. A total of 57.9% (n=11) of the cases and 45.2% (n=19) of the controls presented ED. Patients without ED had a mean increase in brachial artery diameter of 23.16%, while in those with ED it was only 3.84%. Individuals with diabetes or hypertension had a greater thickness of the carotid artery intima media layer (1.092 versus 0.664 cm) ( p =0.037). A positive test for ED was associated with a greater basal diameter of the brachial artery (4.66±0.62 versus 4.23±0.59 cm) ( p =0.02). A total of 7 patients presented paradoxical response, developing posthyperemia vasoconstriction. The proportion of ED was high among controls and among patients with risk

  5. High-Altitude Particle Acceleration and Radiation in Pulsar Slot Gaps

    NASA Technical Reports Server (NTRS)

    Muslimov, Alex G.; Harding, Alice K.

    2004-01-01

    We explore the pulsar slot gap (SG) electrodynamics up to very high altitudes, where for most relatively rapidly rotating pulsars both the standard small-angle approximation and the assumption that the magnetic field lines are ideal stream lines break down. We address the importance of the electrodynamic conditions at the SG boundaries and the occurrence of a steady-state drift of charged particles across the SG field lines at very high altitudes. These boundary conditions and the cross-field particle motion determine the asymptotic behavior of the scalar potential at all radii from the polar cap (PC) to near the light cylinder. As a result, we demonstrate that the steady-state accelerating electric field, E(sub ll), must approach a small and constant value at high altitude above the PC. This E(sub ll) is capable of maintaining electrons moving with high Lorentz factors (approx. a few x 10(exp 7)) and emitting curvature gamma-ray photons up to nearly the light cylinder. By numerical simulations, we show that primary electrons accelerating from the PC surface to high altitude in the SG along the outer edge of the open field region will form caustic emission patterns on the trailing dipole field lines. Acceleration and emission in such an extended SG may form the physical basis of a model that can successfully reproduce some pulsar high-energy light curves.

  6. Study on Oxygen Supply Standard for Physical Health of Construction Personnel of High-Altitude Tunnels.

    PubMed

    Guo, Chun; Xu, Jianfeng; Wang, Mingnian; Yan, Tao; Yang, Lu; Sun, Zhitao

    2015-12-22

    The low atmospheric pressure and low oxygen content in high-altitude environment have great impacts on the functions of human body. Especially for the personnel engaged in complicated physical labor such as tunnel construction, high altitude can cause a series of adverse physiological reactions, which may result in multiple high-altitude diseases and even death in severe cases. Artificial oxygen supply is required to ensure health and safety of construction personnel in hypoxic environments. However, there are no provisions for oxygen supply standard for tunnel construction personnel in high-altitude areas in current tunnel construction specifications. As a result, this paper has theoretically studied the impacts of high-altitude environment on human bodies, analyzed the relationship between labor intensity and oxygen consumption in high-altitude areas and determined the critical oxygen-supply altitude values for tunnel construction based on two different standard evaluation systems, i.e., variation of air density and equivalent PIO₂. In addition, it has finally determined the oxygen supply standard for construction personnel in high-altitude areas based on the relationship between construction labor intensity and oxygen consumption.

  7. Effects of Five Nights under Normobaric Hypoxia on Sleep Quality.

    PubMed

    Hoshikawa, Masako; Uchida, Sunao; Osawa, Takuya; Eguchi, Kazumi; Arimitsu, Takuma; Suzuki, Yasuhiro; Kawahara, Takashi

    2015-07-01

    The purpose of this study was to evaluate the effects of five nights' sleep under normobaric hypoxia on ventilatory acclimatization and sleep quality. Seven men initially slept for six nights under normoxia and then for five nights under normobaric hypoxia equivalent to a 2000-m altitude. Nocturnal polysomnograms (PSGs), arterial blood oxygen saturation (SpO2), and respiratory events were recorded on the first and fifth nights under both conditions. The hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and resting end-tidal CO2 (resting PETCO2) were measured three times during the experimental period. The duration of slow-wave sleep (SWS: stage N3) and the whole-night delta (1-3 Hz) power of nonrapid eye movement (NREM) sleep EEG decreased on the first night under hypoxia. This hypoxia-induced sleep quality deterioration on the first night was accompanied by a lower mean and minimum SpO2, a longer time spent with SpO2 below 90% (<90% SpO2 time), and more episodes of respiratory disturbance. On the fifth night, the SWS duration and whole-night delta power did not differ between the conditions. Although the mean SpO2 under hypoxia was still lower than under normoxia, the minimum SpO2 increased, and the <90% SpO2 time and number of episodes of respiratory disturbance decreased during the five nights under hypoxia. The HVR increased and resting PETCO2 decreased after five nights under hypoxia. The results suggest that five nights under hypoxia improves the sleep quality. This may be derived from improvements of respiratory disturbances, the minimum SpO2, and <90% SpO2 time.

  8. Civilian Training in High-Altitude Flight Physiology

    DOT National Transportation Integrated Search

    1991-08-01

    A survey was conducted to determine if training in high-altitude physiology should : be required for civilian pilots; what the current status of such training was; and, : if required, what should be included in an ideal curriculum. The survey include...

  9. Post-translational modifications of eNOS augment nitric oxide availability and facilitates hypoxia adaptation in Ladakhi women.

    PubMed

    Pooja; Ghosh, Dishari; Bhargava, Kalpana; Sethy, Niroj Kumar

    2018-06-09

    The lower inhaled oxygen per volume at high altitude poses an intimidating challenge for humans to survive and reproduce. Indigenous populations of the Himalayas reportedly exhibit higher microcirculatory blood flow accompanied by higher orders of magnitude of nitric oxide (NO) products in lung, plasma and red blood cells as a vascular adaptation strategy for hypobaric hypoxia. The precise mechanism of such observed higher NO metabolites for hypoxia adaptation remains elusive. Studying high altitude native Ladakhi women, we observed significant higher eNOS mRNA and protein in blood/plasma as compared to lowland women. We also observed higher level of plasma l-citrulline and NOx (nitrates and nitrites) with concomitant lower levels of arginase mRNA and protein further suggesting higher eNOS activity and NO bioavailability. Interestingly, middle aged postmenopausal Ladakhi women exhibited significantly higher level of eNOS activity, NOx and cGMP as compared to age matched lowland women. Preferential phosphorylation of eNOS on stimulatory Ser1177 and Ser615 as well as dephosphorylation of inhibitory Thr495 site contributed to higher NO availability in Ladakhi women irrespective of age. We also observed higher levels of eNOS activating humoral factors like bradykinin and estrogen in both young and middle-aged Ladakhi women. These results suggest that an altered phosphorylation status, together with an enhanced expression of eNOS and potential humoral endothelial activators, are involved in enhanced activation of the eNOS-NO-cGMP pathway in Ladakhi women irrespective of age, reinforcing the hypothesis that NO metabolites play a major role in Himalayan pattern of hypoxia adaptation. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. [Hypoxia and memory. Specific features of nootropic agents effects and their use].

    PubMed

    Voronina, T A

    2000-01-01

    Hypoxia and hypoxic adaptation are powerful factors of controlling memory and behavior processes. Acute hypoxia exerts a differential impact on different deficits of mnestic and cognitive functions. Instrumental reflexes of active and passive avoidance, negative learning, behavior with a change in the stereotype of learning are more greatly damaged. Memory with spatial and visual differentiation and their rearrangement change to a lesser extent and conditional reflexes are not deranged. In this contract, altitude hypoxic adaptation enhances information fixation and increases the degree and duration of retention of temporary relations. Nootropic agents with an antihypoxic action exert a marked effect on hypoxia-induced cognitive and memory disorders and the magnitude of this effect depends on the ration of proper nootropic to antihypoxic components in the spectrum of the drugs' pharmacological activity. The agents that combine a prevailing antiamnestic effect and a marked and moderate antihypoxic action (mexidole, nooglutil, pyracetam, beglymin, etc.) are most effective in eliminating different hypoxia-induced cognitive and memory disorders, nootropic drugs that have a pronounced antiamnestic activity (centrophenoxine, etc.) and no antihypoxic component also restore the main types of mnestic disorders after hypoxia, but to a lesser extent.

  11. Hypoxic preconditioning facilitates acclimatization to hypobaric hypoxia in rat heart.

    PubMed

    Singh, Mrinalini; Shukla, Dhananjay; Thomas, Pauline; Saxena, Saurabh; Bansal, Anju

    2010-12-01

    Acute systemic hypoxia induces delayed cardioprotection against ischaemia-reperfusion injury in the heart. As cobalt chloride (CoCl₂) is known to elicit hypoxia-like responses, it was hypothesized that this chemical would mimic the preconditioning effect and facilitate acclimatization to hypobaric hypoxia in rat heart. Male Sprague-Dawley rats treated with distilled water or cobalt chloride (12.5 mg Co/kg for 7 days) were exposed to simulated altitude at 7622 m for different time periods (1, 2, 3 and 5 days). Hypoxic preconditioning with cobalt appreciably attenuated hypobaric hypoxia-induced oxidative damage as observed by a decrease in free radical (reactive oxygen species) generation, oxidation of lipids and proteins. Interestingly, the observed effect was due to increased expression of the antioxidant proteins hemeoxygenase and metallothionein, as no significant change was observed in antioxidant enzyme activity. Hypoxic preconditioning with cobalt increased hypoxia-inducible factor 1α (HIF-1α) expression as well as HIF-1 DNA binding activity, which further resulted in increased expression of HIF-1 regulated genes such as erythropoietin, vascular endothelial growth factor and glucose transporter. A significant decrease was observed in lactate dehydrogenase activity and lactate levels in the heart of preconditioned animals compared with non-preconditioned animals exposed to hypoxia. The results showed that hypoxic preconditioning with cobalt induces acclimatization by up-regulation of hemeoxygenase 1 and metallothionein 1 via HIF-1 stabilization. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.

  12. Altitude, Gun Ownership, Rural Areas, and Suicide

    PubMed Central

    Kim, Namkug; Mickelson, Jennie B.; Brenner, Barry E.; Haws, Charlotte A.; Yurgelun-Todd, Deborah A.; Renshaw, Perry F.

    2015-01-01

    Objective The authors recently observed a correlation between state altitude and suicide rate in the United States, which could be explained by higher rates of gun ownership and lower population density in the intermountain West. The present study evaluated the relationship between mean county and state altitude in the United States and total age-adjusted suicide rates, firearm-related suicide rates, and non-firearm-related suicide rates. The authors hypothesized that altitude would be significantly associated with suicide rate. Method Elevation data were calculated with an approximate spatial resolution of 0.5 km, using zonal statistics on data sets compiled from the National Geospatial-Intelligence Agency and the National Aeronautics and Space Administration. Suicide and population density data were obtained through the Centers for Disease Control and Prevention (CDC) WONDER database. Gun ownership data were obtained through the CDC’s Behavioral Risk Factor Surveillance System. Results A significant positive correlation was observed between age-adjusted suicide rate and county elevation (r=0.51). Firearm (r=0.41) and non-firearm suicide rates (r=0.32) were also positively correlated with mean county elevation. Conclusions When altitude, gun ownership, and population density are considered as predictor variables for suicide rates on a state basis, altitude appears to be a significant independent risk factor. This association may be related to the effects of metabolic stress associated with mild hypoxia in individuals with mood disorders. PMID:20843869

  13. High altitude solar power platform. [aircraft design analysis

    NASA Technical Reports Server (NTRS)

    Bailey, M. D.; Bower, M. V.

    1992-01-01

    Solar power is a preeminent alternative to conventional aircraft propulsion. With the continued advances in solar cells, fuel cells, and composite materials technology, the solar powered airplane is no longer a simple curiosity constrained to flights of several feet in altitude or minutes of duration. A high altitude solar powered platform (HASPP) has several potential missions, including communications and agriculture. In remote areas, a HASPP could be used as a communication link. In large farming areas, a HASPP could perform remote sensing of crops. The impact of HASPP in continuous flight for one year on agricultural monitoring mission is presented. This mission provides farmers with near real-time data twice daily from an altitude which allows excellant resolution on water conditions, crop diseases, and insect infestation. Accurate, timely data will enable farmers to increase their yield and efficiency. A design for HASPP for the foregoing mission is presented. In the design power derived from solar cells covering the wings is used for propulsion, avionics, and sensors. Excess power produced midday will be stored in fuel cells for use at night to maintain altitude and course.

  14. Effect of egg composition and oxidoreductase on adaptation of Tibetan chicken to high altitude.

    PubMed

    Jia, C L; He, L J; Li, P C; Liu, H Y; Wei, Z H

    2016-07-01

    Tibetan chickens have good adaptation to hypoxic conditions, which can be reflected by higher hatchability than lowland breeds when incubated at high altitude. The objective of this trial was to study changes in egg composition and metabolism with regards the adaptation of Tibetan chickens to high altitude. We measured the dry weight of chicken embryos, egg yolk, and egg albumen, and the activity of lactate dehydrogenase (LDH) and succinic dehydrogenase (SDH) in breast muscle, heart, and liver from embryos of Tibetan chicken and Dwarf chicken (lowland breed) incubated at high (2,900 m) and low (100 m) altitude. We found that growth of chicken embryos was restricted at high altitude, especially for Dwarf chicken embryos. In Tibetan chicken, the egg weight was lighter, but the dry weight of egg yolk was heavier than that of Dwarf chicken. The LDH activities of the three tissues from the high altitude groups were respectively higher than those of the lowland groups from d 15 to hatching, except for breast muscle of Tibetan chicken embryos on d 15. In addition, under the high altitude environment, the heart tissue from Tibetan chicken had lower LDH activity than that from Dwarf chicken at d 15 and 18. The lactic acid content of blood from Tibetan chicken embryos was lower than that of Dwarf chicken at d 12 and 15 of incubation at high altitude. There was no difference in SDH activity in the three tissues between the high altitude groups and the lowland groups except in three tissues of hatchlings and at d 15 of incubation in breast muscle, nor between the two breeds at high altitude except in the heart of hatchlings. Consequently, the adaptation of Tibetan chicken to high altitude may be associated with higher quantities of yolk in the egg and a low metabolic oxygen demand in tissue, which illuminate the reasons that the Tibetan chicken have higher hatchability with lower oxygen transport ability. © 2016 Poultry Science Association Inc.

  15. Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia.

    PubMed

    Santos, S A; Silva, E T; Caris, A V; Lira, F S; Tufik, S; Dos Santos, R V T

    2016-08-01

    Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P < 0.05). Supplementation decreased creatine kinase (CK)-TOTAL, CK-MB and lactate dehydrogenase 1 h after exercise (P < 0.05). The exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P < 0.05). Supplementation reversed the changes observed after exercise in hypoxia without supplementation (P < 0.05). We conclude that 250 mg of vitamin E supplementation at 1 h before exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise. © 2016 The British Dietetic Association Ltd.

  16. Butterflies of the high-altitude Atacama Desert: habitat use and conservation

    PubMed Central

    Despland, Emma

    2014-01-01

    The butterfly fauna of the high-altitude desert of Northern Chile, though depauperate, shows high endemism, is poorly known and is of considerable conservation concern. This study surveys butterflies along the Andean slope between 2400 and 5000 m asl (prepuna, puna and Andean steppe habitats) as well as in high and low-altitude wetlands and in the neoriparian vegetation of agricultural sites. We also include historical sightings from museum records. We compare abundances between altitudes, between natural and impacted sites, as well as between two sampling years with different precipitation regimes. The results confirm high altitudinal turnover and show greatest similarity between wetland and slope faunas at similar altitudes. Results also underscore vulnerability to weather fluctuations, particularly in the more arid low-altitude sites, where abundances were much lower in the low precipitation sampling season and several species were not observed at all. Finally, we show that some species have shifted to the neoriparian vegetation of the agricultural landscape, whereas others were only observed in less impacted habitats dominated by native plants. These results suggest that acclimation to novel habitats depends on larval host plant use. The traditional agricultural environment can provide habitat for many, but not all, native butterfly species, but an estimation of the value of these habitats requires better understanding of butterfly life history strategies and relationships with host plants. PMID:25309583

  17. Respiratory function in pregnancy at sea level and at high altitude.

    PubMed

    McAuliffe, Fionnuala; Kametas, Nikos; Espinoza, Jimmy; Greenough, Anne; Nicolaides, Kypros

    2004-04-01

    To determine the effect of pregnancy on respiratory function in a non-Caucasian group and determine whether there was an interaction between pregnancy and altitude of residence. Prospective cross sectional study. Antenatal clinics in Peru, at sea level in Lima and at high altitude in Cerro de Pasco. Peruvian women with singleton pregnancies; 122 living at sea level and 192 living at 4300 m altitude in the Peruvian Andes. At each location, 19 non-pregnant women were also studied. Respiratory function was measured in pregnant and non-pregnant women living at sea level and at 4300 m. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), total lung capacity (TLC), inspiratory capacity (IC), residual volume (RV), expiratory residual volume (ERV) and functional residual capacity (FRC). At sea level, RV and TLC were higher in the third compared with the first trimester (P < 0.05). At high altitude, FEV1 (P < 0.01), ERV (P < 0.01) and FRC (P < 0.01) were lower in the third compared with the first trimester. Pregnant and non-pregnant women at high altitude were 4 cm shorter (P < 0.0001) and had larger lung volumes (P < 0.01); their total lung capacities were approximately 1 L greater than women living at sea level (P < 0.0001). These results suggest that the effect of pregnancy on the respiratory function of healthy women is influenced by altitude of residence.

  18. High-Altitude Flight Cooling Investigation of a Radial Air-Cooled Engine

    NASA Technical Reports Server (NTRS)

    Manganiello, Eugene J; Valerino, Michael F; Bell, E Barton

    1947-01-01

    An investigation of the cooling of an 18-cylinder, twin-row, radial, air-cooled engine in a high-performance pursuit airplane has been conducted for variable engine and flight conditions at altitudes ranging from 5000 to 35,000 feet in order to provide a basis for predicting high-altitude cooling performance from sea-level or low altitude experimental results. The engine cooling data obtained were analyzed by the usual NACA cooling-correlation method wherein cylinder-head and cylinder-barrel temperatures are related to the pertinent engine and cooling-air variables. A theoretical analysis was made of the effect on engine cooling of the change of density of the cooling air across the engine (the compressibility effect), which becomes of increasing importance as altitude is increased. Good agreement was obtained between the results of the theoretical analysis and the experimental data.

  19. Oxidative phosphorylation of liver mitochondria from mice acclimatized to hypobaric hypoxia

    NASA Astrophysics Data System (ADS)

    Leon-Velarde, F.; Whittembury, J.; Monge, C.

    1986-09-01

    Mice exposed to intermittent hypobaric hypoxia for 20 hours a day, 6 days a week, develop extracellular adaptive responses similar to those found in humans exposed to oxygen tension equivalent to that found at an altitude of 4500 m. Isolated liver mitochondria from these animals show no significant differences in rates of substrate-stimulated respiration, ADP-stimulated respiration and the respiratory control ratio (RCR), when compared with sea level controls. Undetectable or negligible differences in these parameters are also noted when sea level animals are exposed for one hour to severe hypoxia (7% O2). We therefore conclude that the oxidative phosphorylation capacity of the isolated mouse liver mitochondria remains unaltered in both acute and chronic hypoxia. However the in vivo oxygen consumption by mice at this degree of hypoxia was markedly reduced. Lack of observable changes in oxidative phosphorylation could be accounted for by extracellular adaptations in mitochondria isolated from acclimatized animals. This explanation, however, is not consistent with the lack of changes on oxidative phosphorylation in mitochondria isolated from mice undergoing acute hypoxia at sea level. It is then suggested that isolated mitochondrial preparations are of limited value for investigating biochemical mechanisms underlying the variation of cellular respiration occurring in vivo.

  20. Decreased steady-state cerebral blood flow velocity and altered dynamic cerebral autoregulation during 5-h sustained 15% O2 hypoxia.

    PubMed

    Nishimura, Naoko; Iwasaki, Ken-ichi; Ogawa, Yojiro; Aoki, Ken

    2010-05-01

    Effects of hypoxia on cerebral circulation are important for occupational, high-altitude, and aviation medicine. Increased risk of fainting might be attributable to altered cerebral circulation by hypoxia. Dynamic cerebral autoregulation is reportedly impaired immediately by mild hypoxia. However, continuous exposure to hypoxia causes hyperventilation, resulting in hypocapnia. This hypocapnia is hypothesized to restore impaired dynamic cerebral autoregulation with reduced steady-state cerebral blood flow (CBF). However, no studies have examined hourly changes in alterations of dynamic cerebral autoregulation and steady-state CBF during sustained hypoxia. We therefore examined cerebral circulation during 5-h exposure to 15% O2 hypoxia and 21% O2 in 13 healthy volunteers in a sitting position. Waveforms of blood pressure and CBF velocity in the middle cerebral artery were measured using finger plethysmography and transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis. As expected, steady-state CBF velocity decreased significantly from 2 to 5 h of hypoxia, accompanying 2- to 3-Torr decreases in end-tidal CO2 (ETCO2). Furthermore, transfer function gain and coherence in the very-low-frequency range increased significantly at the beginning of hypoxia, indicating impaired dynamic cerebral autoregulation. However, contrary to the proposed hypothesis, indexes of dynamic cerebral autoregulation showed no significant restoration despite ETCO2 reductions, resulting in persistent higher values of very-low-frequency power of CBF velocity variability during hypoxia (214+/-40% at 5 h of hypoxia vs. control) without significant increases in blood pressure variability. These results suggest that sustained mild hypoxia reduces steady-state CBF and continuously impairs dynamic cerebral autoregulation, implying an increased risk of shortage of oxygen supply to the brain.

  1. Admixture facilitates genetic adaptations to high altitude in Tibet

    PubMed Central

    Jeong, Choongwon; Alkorta-Aranburu, Gorka; Basnyat, Buddha; Neupane, Maniraj; Witonsky, David B.; Pritchard, Jonathan K.; Beall, Cynthia M.; Di Rienzo, Anna

    2015-01-01

    Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower hemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here, we analyze genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive hemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments. PMID:24513612

  2. Gondola for High Altitude Planetary Science (GHAPS)

    NASA Technical Reports Server (NTRS)

    Hoffmann, Monica

    2017-01-01

    Description of the NASA Gondola for High Altitude Planetary Science (GHAPS) balloon project and its planetary science capabilities provided in a poster or fact sheet format as needed. The ability of GHAPS to provide a re-useable platform to collect planetary information is described.

  3. Hypoxia and training-induced adaptation of hormonal responses to exercise in humans.

    PubMed

    Engfred, K; Kjaer, M; Secher, N H; Friedman, D B; Hanel, B; Nielsen, O J; Bach, F W; Galbo, H; Levine, B D

    1994-01-01

    To establish whether or not hypoxia influences the training-induced adaptation of hormonal responses to exercise, 21 healthy, untrained subjects (2) years, mean (SE)] were studied in three groups before and after 5 weeks' training (cycle ergometer, 45 min.day-1, 5 days.week-1). Group 1 trained at sea level at 70% maximal oxygen uptake (VO2max), group 2 in a hypobaric chamber at a simulated altitude of 2500 m at 70% of altitude VO2max, and group 3 at a simulated altitude of 2500 m at the same absolute work rate as group 1. Arterial blood was sampled before, during and at the end of exhaustive cycling at sea level (85% of pretraining VO2max). VO2max increased by 12 (2)% with no significant difference between groups, whereas endurance improved most in group 1 (P < 0.05). Training-induced changes in response to exercise of noradrenaline, adrenaline, growth hormone, beta-endorphin, glucagon, and insulin were similar in the three groups. Concentrations of erythropoietin and 2,3-diphosphoglycerate at rest did not change over the training period. In conclusion, within 5 weeks of training, no further adaptation of hormonal exercise responses takes place if intensity is increased above 70% VO2max. Furthermore, hypoxia per se does not add to the training-induced hormonal responses to exercise.

  4. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

    PubMed

    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. © 2013.

  5. Canadian Academy of Sport and Exercise Medicine position statement: athletes at high altitude.

    PubMed

    Koehle, Michael S; Cheng, Ivy; Sporer, Benjamin

    2014-03-01

    Many sports incorporate training at altitude as a key component of their athlete training plan. Furthermore, many sports are required to compete at high altitude venues. Exercise at high altitude provides unique challenges to the athlete and to the sport medicine clinician working with these athletes. These challenges include altitude illness, alterations in training intensity and performance, nutritional and hydration difficulties, and challenges related to the austerity of the environment. Furthermore, many of the strategies that are typically utilized by visitors to altitude may have implications from an anti-doping point of view.This position statement was commissioned and approved by the Canadian Academy of Sport and Exercise Medicine. The purpose of this statement was to provide an evidence-based, best practices summary to assist clinicians with the preparation and management of athletes and individuals travelling to altitude for both competition and training.

  6. Text mining and network analysis to find functional associations of genes in high altitude diseases.

    PubMed

    Bhasuran, Balu; Subramanian, Devika; Natarajan, Jeyakumar

    2018-05-02

    Travel to elevations above 2500 m is associated with the risk of developing one or more forms of acute altitude illness such as acute mountain sickness (AMS), high altitude cerebral edema (HACE) or high altitude pulmonary edema (HAPE). Our work aims to identify the functional association of genes involved in high altitude diseases. In this work we identified the gene networks responsible for high altitude diseases by using the principle of gene co-occurrence statistics from literature and network analysis. First, we mined the literature data from PubMed on high-altitude diseases, and extracted the co-occurring gene pairs. Next, based on their co-occurrence frequency, gene pairs were ranked. Finally, a gene association network was created using statistical measures to explore potential relationships. Network analysis results revealed that EPO, ACE, IL6 and TNF are the top five genes that were found to co-occur with 20 or more genes, while the association between EPAS1 and EGLN1 genes is strongly substantiated. The network constructed from this study proposes a large number of genes that work in-toto in high altitude conditions. Overall, the result provides a good reference for further study of the genetic relationships in high altitude diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Oxidative stress in erythrocytes: a study on the effect of antioxidant mixtures during intermittent exposures to high altitude

    NASA Astrophysics Data System (ADS)

    Vani, R.; Shiva Shankar Reddy, C. S.; Asha Devi, S.

    2010-09-01

    The aim of our study was to compare and assess the effectiveness of antioxidant mixtures on the erythrocytes (RBC) of adult male albino rats (Wister) subjected to simulated intermittent high altitudes—5,100 m (AL1) and 6,700 m (AL2)—to induce oxidative stress (OS). To achieve our objective, we pre-supplemented four sets of animals with different antioxidant mixtures [vitamin E (vit.E; 50 IU/kg BW), vitamin C (vit.C; 400 mg/kg) and l-carnitine (400 mg/kg)] in different combinations [M1 (vit.E+vit.C), M2 (vit.C+carnitine), M3 (vit.E+carnitine) and M4 (vit.C+vit.E+carnitine)] for 30 days prior to as well during exposure to intermittent hypobaric hypoxia (IHH). Membrane instability, in terms of osmotic fragility and hemolysis, decreased in RBCs of supplemented animals. There was a significant increase in the activity of glutathione peroxidase in the RBCs of supplemented animals. We confirmed OS imposed by IHH with assays relating to lipid [thiobarbituric acid reactive substances (TBARS) and lipofuscin (LF)] and protein (carbonyl, PrC) oxidation, and found a positive correlation between PrC and hemolysis, with a decrease in both upon supplementation with M3 and M4 mixtures. Fluorescence microscopic observation showed a maximum decrease in the LF content in rats administered M4 and M1 compared to those on M2 and M3 mixtures at both altitudes. We suggest that multiple antioxidant fortifications are effective in overcoming increased OS experienced by RBCs at high altitudes.

  8. Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Cintron, N. M.; Pietrzyk, R. A.; Scotto, P.; Loeppky, J. A.

    1994-01-01

    In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

  9. Effect of phosphate supplementation on oxygen delivery at high altitude

    NASA Astrophysics Data System (ADS)

    Jain, S. C.; Singh, M. V.; Rawal, S. B.; Sharma, V. M.; Divekar, H. M.; Tyagi, A. K.; Panwar, M. R.; Swamy, Y. V.

    1987-09-01

    In the present communication, effect of low doses of phosphate supplementation on short-term high altitude adaptation has been examined. Studies were carried out in 36 healthy, male, sea-level residents divided in a double blind fashion into drug and placebo treated groups. 3.2 mmol of phosphate were given orally to each subject of the drug treated group once a day for 4 days on arrival at an altitude of 3,500 m. Sequential studies were done in the subjects in both groups on the 3rd, 7th, 14th and 21st day of their altitude stay. Haemoglobin, haematocrit, erythrocyte and reticulocyte counts increased to the similar extent in both groups. Blood pH, pO2 and adenosine tri-phosphate (ATP) did not differ between the two groups. On 3rd day of the altitude stay, inorganic phosphate and 2,3-diphosphoglycerate (2,3 DPG) levels in the drug treated group increased significantly as compared to the placebo group. No significant difference in inorganic phosphate and 2,3 DPG was observed later on in the two groups. Psychological and clinical tests also indicated that the drug treated subjects felt better as compared to the placebo treated subjects. The present study suggests that low doses of phosphate increases circulating 2,3-DPG concentration which in turn brings about beneficial effect towards short term high altitude adaptation.

  10. Piloted simulation study of a balloon-assisted deployment of an aircraft at high altitude

    NASA Technical Reports Server (NTRS)

    Murray, James; Moes, Timothy; Norlin, Ken; Bauer, Jeffrey; Geenen, Robert; Moulton, Bryan; Hoang, Stephen

    1992-01-01

    A piloted simulation was used to study the feasibility of a balloon assisted deployment of a research aircraft at high altitude. In the simulation study, an unmanned, modified sailplane was carried to 110,000 ft with a high altitude balloon and released in a nose down attitude. A remote pilot controlled the aircraft through a pullout and then executed a zoom climb to a trimmed, 1 g flight condition. A small parachute was used to limit the Mach number during the pullout to avoid adverse transonic effects. The use of small rocket motor was studied for increasing the maximum attainable altitude. Aerodynamic modifications to the basic sailplane included applying supercritical airfoil gloves over the existing wing and tail surfaces. The aerodynamic model of the simulated aircraft was based on low Reynolds number wind tunnel tests and computational techniques, and included large Mach number and Reynolds number effects at high altitude. Parametric variations were performed to study the effects of launch altitude, gross weight, Mach number limit, and parachute size on the maximum attainable stabilized altitude. A test altitude of approx. 95,000 ft was attained, and altitudes in excess of 100,000 ft was attained.

  11. Differences in Hematological Traits between High- and Low-Altitude Lizards (Genus Phrynocephalus)

    PubMed Central

    Lu, Songsong; Xin, Ying; Tang, Xiaolong; Yue, Feng; Wang, Huihui; Bai, Yucheng; Niu, Yonggang; Chen, Qiang

    2015-01-01

    Phrynocephalus erythrurus (Lacertilia: Agamidae) is considered to be the highest living reptile in the world (about 4500-5000 m above sea level), whereas Phrynocephalus przewalskii inhabits low altitudes (about 1000-1500 m above sea level). Here, we report the differences in hematological traits between these two different Phrynocephalus species. Compared with P. przewalskii, the results indicated that P. erythrurus own higher oxygen carrying capacity by increasing red blood cell count (RBC), hemoglobin concentration ([Hb]) and hematocrit (Hct) and these elevations could promote oxygen carrying capacity without disadvantage of high viscosity. The lower partial pressure of oxygen in arterial blood (PaO2) of P. erythrurus did not cause the secondary alkalosis, which may be attributed to an efficient pulmonary system for oxygen (O2) loading. The elevated blood-O2 affinity in P. erythrurus may be achieved by increasing intrinsic O2 affinity of isoHbs and balancing the independent effects of potential heterotropic ligands. We detected one α-globin gene and three β-globin genes with 1 and 33 amino acid substitutions between these two species, respectively. Molecular dynamics simulation results showed that amino acids substitutions in β-globin chains could lead to the elimination of hydrogen bonds in T-state Hb models of P. erythrurus. Based on the present data, we suggest that P. erythrurus have evolved an efficient oxygen transport system under the unremitting hypobaric hypoxia. PMID:25955247

  12. An Investigation into the Nature of High Altitude Cosmic Radiation in the Stratosphere

    ERIC Educational Resources Information Center

    Bancroft, Samuel; Bancroft, Ben; Greenwood, Jake

    2014-01-01

    An experiment was carried out to investigate the changes in ionizing cosmic radiation as a function of altitude. This was carried out using a Geiger-Müller tube on-board a high altitude balloon, which rose to an altitude of 31 685 m. The gathered data show that the Geiger-Müller tube count readings increased to a maximum at an altitude of about 24…

  13. Atypical hematological response to combined calorie restriction and chronic hypoxia in Biosphere 2 crew: a possible link to latent features of hibernation capacity.

    PubMed

    Paglia, Donald E; Walford, Roy L

    2005-01-01

    Eight humans were isolated for 2 years in Biosphere 2, a sealed airtight habitat with recycled air, food, water, and wastes. A combination of conditions led to selective decline of oxygen (O2) in the internal atmosphere from 21% to 14%, inducing symptoms of high-altitude sickness but with little or no compensatory increase in red cell production. All crew members exhibited significant decreases in both erythrocyte 2,3-bisphosphoglycerate (2,3-BPG) concentrations and P50 [partial pressure of O2 for 50% hemoglobin (Hb) saturation] values, changes opposite those expected in adaptation to high-altitude hypoxia. Lower P50 with increased Hb-O2 affinity induced by low 2,3-BPG is a characteristic of hibernating species and could be advantageous in O2-impoverished environments. The mechanisms underlying these changes in the Biosphere 2 crew remain obscure but could be related to low-calorie diet (1750-2100 kcal/day). Because the combination of hypoxia and limited caloric intake is also characteristic of hibernation, this unusual response may represent a cross-adaptation phenomenon in which certain features of hibernation capability are expressed in humans.

  14. High Altitude Balloons as a Platform for Space Radiation Belt Science

    NASA Astrophysics Data System (ADS)

    Mazzino, L.; Buttenschoen, A.; Farr, Q.; Hodgson, C.; Johnson, W.; Mann, I. R.; Rae, J.; University of Alberta High Altitude Balloons (UA-HAB)

    2011-12-01

    The goals of the University of Alberta High Altitude Balloons Program (UA-HAB) are to i) use low cost balloons to address space radiation science, and ii) to utilise the excitement of "space mission" involvement to promote and facilitate the recruitment of undergraduate and graduate students in physics, engineering, and atmospheric sciences to pursue careers in space science and engineering. The University of Alberta High Altitude Balloons (UA-HAB) is a unique opportunity for University of Alberta students (undergraduate and graduate) to engage in the hands-on design, development, build, test and flight of a payload to operate on a high altitude balloon at around 30km altitude. The program development, including formal design and acceptance tests, reports and reviews, mirror those required in the development of an orbital satellite mission. This enables the students to gain a unique insight into how space missions are flown. UA-HAB is a one and half year program that offers a gateway into a high-altitude balloon mission through hands on experience, and builds skills for students who may be attracted to participate in future space missions in their careers. This early education will provide students with the experience necessary to better assess opportunities for pursuing a career in space science. Balloons offer a low-cost alternative to other suborbital platforms which can be used to address radiation belt science goals. In particular, the participants of this program have written grant proposal to secure funds for this project, have launched several 'weather balloon missions', and have designed, built, tested, and launched their particle detector called "Maple Leaf Particle Detector". This detector was focussed on monitoring cosmic rays and space radiation using shielded Geiger tubes, and was flown as one of the payloads from the institutions participating in the High Altitude Student Platform (HASP), organized by the Louisiana State University and the Louisiana

  15. Relative Match Intensities at High Altitude in Highly-Trained Young Soccer Players (ISA3600).

    PubMed

    Buchheit, Martin; Hammond, Kristal; Bourdon, Pitre C; Simpson, Ben M; Garvican-Lewis, Laura A; Schmidt, Walter F; Gore, Christopher J; Aughey, Robert J

    2015-03-01

    To compare relative match intensities of sea-level versus high-altitude native soccer players during a 2-week camp at 3600 m, data from 7 sea-level (Australian U17 National team, AUS) and 6 high-altitude (a Bolivian U18 team, BOL) native soccer players were analysed. Two matches were played at sea-level and three at 3600 m on Days 1, 6 and 13. The Yo-Yo Intermittent recovery test (vYo-YoIR1) was performed at sea-level, and on Days 3 and 10. Match activity profiles were measured via 10-Hz GPS. Distance covered >14.4 km.h(-1) (D>14.4 km·h(-1)) and >80% of vYo-YoIR1 (D>80%vYo-YoIR1) were examined. Upon arrival at altitude, there was a greater decrement in vYo-YoIR1 (Cohen's d +1.0, 90%CL ± 0.8) and D>14.4 km·h(-1) (+0.5 ± 0.8) in AUS. D>14.4 km.h(-1) was similarly reduced relative to vYo-YoIR1 in both groups, so that D>80%vYo-YoIR1 remained similarly unchanged (-0.1 ± 0.8). Throughout the altitude sojourn, vYo-YoIR1 and D>14.4 km·h(-1) increased in parallel in AUS, so that D>80%vYo-YoIR1 remained stable in AUS (+6.0%/match, 90%CL ± 6.7); conversely D>80%vYo-YoIR1 decreased largely in BOL (-12.2%/match ± 6.2). In sea-level natives competing at high-altitude, changes in match running performance likely follow those in high-intensity running performance. Bolivian data confirm that increases in 'fitness' do not necessarily translate into greater match running performance, but rather in reduced relative exercise intensity. Key pointsWhen playing at high-altitude, players may alter their activities during matches in relation to their transient maximal physical capacities, possibly to maintain a 'tolerable' relative exercise intensity.While there is no doubt that running performance per se in not the main determinant of match outcomes (Carling, 2013), fitness levels influence relative match intensity (Buchheit et al., 2012, Mendez-Villanueva et al., 2013), which in-turn may impact on decision making and skill performance (Rampinini et al., 2008).In the context of

  16. Sleeping in moderate hypoxia at home for prevention of acute mountain sickness (AMS): a placebo-controlled, randomized double-blind study.

    PubMed

    Dehnert, Christoph; Böhm, Astrid; Grigoriev, Igor; Menold, Elmar; Bärtsch, Peter

    2014-09-01

    Acclimatization at natural altitude effectively prevents acute mountain sickness (AMS). It is, however, unknown whether prevention of AMS is also possible by only sleeping in normobaric hypoxia. In a placebo-controlled, double-blind study 76 healthy unacclimatized male subjects, aged 18 to 50 years, slept for 14 consecutive nights at either a fractional inspired oxygen (Fio2) of 0.14 to 0.15 (average target altitude 3043 m; treatment group) or 0.209 (control group). Four days later, AMS scores and incidence of AMS were assessed during a 20-hour exposure in normobaric hypoxia at Fio2 = 0.12 (equivalent to 4500 m). Because of technical problems with the nitrogen generators, target altitude was not achieved in the tents and only 21 of 37 subjects slept at an average altitude considered sufficient for acclimatization (>2200 m; average, 2600 m). Therefore, in a subgroup analysis these subjects were compared with the 21 subjects of the control group with the lowest sleeping altitude. This analysis showed a significantly lower AMS-C score (0.38; 95% CI, 0.21 to 0.54) vs 1.10; 95% CI, 0.57 to 1.62; P = .04) and lower Lake Louise Score (3.1; 95% CI, 2.2 to 4.1 vs 5.1; 95% CI, 3.6 to 6.6; P = .07) for the treatment subgroup. The incidence of AMS defined as an AMS-C score greater than 0.70 was also significantly lower (14% vs 52%; P < .01). Sleeping 14 consecutive nights in normobaric hypoxia (equivalent to 2600 m) reduced symptoms and incidence of AMS 4 days later on exposure to 4500 m. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  17. Respiratory parameters at varied altitudes in intermittent mining work.

    PubMed

    Bacaloni, Alessandro; Zamora Saà, Margarita Cecilia; Sinibaldi, Federica; Steffanina, Alessia; Insogna, Susanna

    2018-01-07

    Workers in the mining industry in altitude are subjected to several risk factors, e.g., airborne silica and low barometric pressure. The aim of this study has been to assess the risks for this work category, evaluating single risk factors as airborne silica, altitude and work shift, and relating them with cardiovascular and ventilatory parameters. Healthy miners employed in a mining company, Chile, working at varied altitudes, and subjected to unusual work shifts, were evaluated. Cardiovascular and respiratory parameters were investigated. Exposure to airborne silica was evaluated and compared to currently binding exposure limits. At varied altitudes and work shifts, alterations emerged in haemoglobin, ventilation and respiratory parameters, related to employment duration, due to compensatory mechanisms for hypoxia. Haemoglobin increased with altitude, saturation fell down under 90% in the highest mines. The multiple linear regression analysis showed a direct relationship, in the higher mine, between years of exposure to altitude and increased forced vital capacity percent (FVC%), and forced expiratory volume in 1 s (FEV1). An inverse relationship emerged between forced vital capacity (FVC) and years of exposure to airborne silica. In the workplace Mina Subterrànea (MT-3600), statistically significant inverse relationship emerged between the Tiffeneau index and body weight. The working conditions in the mining industry in altitude appeared to be potentially pathogenic; further investigations should be realized integrating risk assessment protocols even in consideration of their undeniable unconventionality. Int J Occup Med Environ Health 2018;31(2):129-138. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  18. The effect of hypobaric hypoxia on multichannel EEG signal complexity.

    PubMed

    Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Maglaveras, Nikos; Pappas, Konstantinos

    2007-01-01

    The objective of this study was the development and evaluation of nonlinear electroencephalography parameters which assess hypoxia-induced EEG alterations, and describe the temporal characteristics of different hypoxic levels' residual effect upon the brain electrical activity. Multichannel EEG, pO2, pCO2, ECG, and respiration measurements were recorded from 10 subjects exposed to three experimental conditions (100% oxygen, hypoxia, recovery) at three-levels of reduced barometric pressure. The mean spectral power of EEG under each session and altitude were estimated for the standard bands. Approximate Entropy (ApEn) of EEG segments was calculated, and the ApEn's time-courses were smoothed by a moving average filter. On the smoothed diagrams, parameters were defined. A significant increase in total power and power of theta and alpha bands was observed during hypoxia. Visual interpretation of ApEn time-courses revealed a characteristic pattern (decreasing during hypoxia and recovering after oxygen re-administration). The introduced qEEG parameters S1 and K1 distinguished successfully the three hypoxic conditions. The introduced parameters based on ApEn time-courses are assessing reliably and effectively the different hypoxic levels. ApEn decrease may be explained by neurons' functional isolation due to hypoxia since decreased complexity corresponds to greater autonomy of components, although this interpretation should be further supported by electrocorticographic animal studies. The introduced qEEG parameters seem to be appropriate for assessing the hypoxia-related neurophysiological state of patients in the hyperbaric chambers in the treatment of decompression sickness, carbon dioxide poisoning, and mountaineering.

  19. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju, E-mail: anjubansaldipas@gmail.com

    High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmentedmore » the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training.

  20. Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia

    PubMed Central

    Treml, Benedikt; Kleinsasser, Axel; Stadlbauer, Karl-Heinz; Steiner, Iris; Pajk, Werner; Pilch, Michael; Burtscher, Martin; Knotzer, Hans

    2018-01-01

    As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1–19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5–40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after

  1. Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.

    PubMed

    Riley, Callum James; Gavin, Matthew

    2017-06-01

    Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 18:102-113, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.

  2. High altitude environmental monitoring: the SHARE project and CEOP-HE

    NASA Astrophysics Data System (ADS)

    Tartari, G.

    2009-04-01

    Mountain areas above 2,500 m a.s.l. constitute about 25% of the Earth's surface and play a fundamental role in the global water balance, while influencing global climate and atmospheric circulation systems. Several millions, including lowlanders, are directly affected by the impacts of climate change on glaciers and water resource distribution. Mountains and high altitude plateaus are subject to the highest rate of temperature increase (e.g., Tibetan Plateau) and are recognized as particularly vulnerable to the effects of climate change. In spite of this, the number of permanent monitoring sites in the major environmental networks decreases with altitude. On a sample of two hundred high altitude automatic weather stations located above 2,500 m a.s.l., less than 20% are over 4,000 m, while there are only 24 stations in the world that could be considered "complete" high altitude observatories. Furthermore, entire mountain areas are left uncovered, creating significant data gaps which make reliable modelling and forecasting nearly impossible. In response to these problems, Ev-K2-CNR has developed the project SHARE (Stations at High Altitude for Research on the Environment) with the support of the Italian government and in collaboration with UNEP. This integrated environmental monitoring and research project aims to improve knowledge on the local, regional and global consequences of climate change in mountain regions and on the influence of high elevations on climate, atmospheric circulation and hydrology. SHARE today boasts a network of 13 permanent monitoring stations between 2,165 m and 8,000 m. Affiliated researchers have produced over 150 scientific publications in atmospheric sciences, meteorology and climate, glaciology, limnology and paleolimnology and geophysics. SHARE network data is also contributed to international programs (UNEP-ABC, WMO-GAW, WCRP-GEWEX-CEOP, NASA-AERONET, ILTER, EU-EUSAAR, EU-ACCENT). Within this context, the CEOP-High Elevations (CEOP

  3. Hypoxia, hypoxia-inducible factors and fibrogenesis in chronic liver diseases.

    PubMed

    Cannito, Stefania; Paternostro, Claudia; Busletta, Chiara; Bocca, Claudia; Colombatto, Sebastiano; Miglietta, Antonella; Novo, Erica; Parola, Maurizio

    2014-01-01

    Fibrogenic progression of chronic liver diseases (CLDs) towards the end-point of cirrhosis is currently regarded, whatever the aetiology, as a dynamic and highly integrated cellular response to chronic liver injury. Liver fibrogenesis (i.e., the process) is sustained by hepatic populations of highly proliferative, pro-fibrogenic and contractile myofibroblast-like cells (MFs) that mainly originate from hepatic stellate cells (HSC) or, to a less extent, from portal fibroblasts or bone marrow-derived cells. As is well known, liver fibrosis (i.e., the result) is accompanied by perpetuation of liver injury, chronic hepatitis and persisting activation of tissue repair mechanisms, leading eventually to excess deposition of extracellular matrix (ECM) components. In this scenario, hypoxic areas represent a very common and major feature of fibrotic and cirrhotic liver during the progression of CLDs. Cells exposed to hypoxia respond by means of heterodimeric hypoxia-inducible factors (HIFs) that translocate into the nucleus and binds to a specific core sequence defined hypoxia-responsive element (HRE), present in the promoter on several genes which are considered as hypoxia-regulated target genes. HIFs transcription factors can activate a complex genetic program designed to sustain several changes necessary to efficiently counteract the decrease in oxygen tension. Accordingly, hypoxia, through up-regulation of angiogenesis, is currently believed to significantly contribute to fibrogenic progression of CLDs, mostly by affecting the pro-fibrogenic and pro-angiogenic behaviour of hepatic MFs. In addition, experimental and clinical evidence generated in the last decade also indicates that angiogenesis and fibrogenesis in CLDs may also be sustained by HIF-dependent but hypoxia-independent mediators.

  4. Turbojet Performance and Operation at High Altitudes with Hydrogen and Jp-4 Fuels

    NASA Technical Reports Server (NTRS)

    Fleming, W A; Kaufman, H R; Harp, J L , Jr; Chelko, L J

    1956-01-01

    Two current turbojet engines were operated with gaseous-hydrogen and JP-4 fuels at very high altitudes and a simulated Mach number of 0.8. With gaseous hydrogen as the fuel stable operation was obtained at altitudes up to the facility limit of about 90,000 feet and the specific fuel consumption was only 40 percent of that with JP-4 fuel. With JP-4 as the fuel combustion was unstable at altitudes above 60,000 to 65,000 feet and blowout limits were reached at 75,000 to 80,000 feet. Over-all performance, component efficiencies, and operating range were reduced considerable at very high altitudes with both fuels.

  5. Polysomnography in Bolivian Children Native to High Altitude Compared to Children Native to Low Altitude.

    PubMed

    Hill, Catherine Mary; Carroll, Annette; Dimitriou, Dagmara; Gavlak, Johanna; Heathcote, Kate; L'Esperance, Veline; Baya, Ana; Webster, Rebecca; Pushpanathan, Maria; Bucks, Romola Starr

    2016-12-01

    To compare polysomnographic parameters in high altitude (HA) native Andean children with low altitude (LA) native peers in order to explain the nocturnal oxyhemoglobin saturation (SpO2) instability reported in HA native children and to study the effect on sleep quality. Ninety-eight healthy children aged 7-10 y and 13-16 y were recruited at LA (500 m) or HA (3,650 m) above sea level. Physical examination was undertaken and genetic ancestry determined from salivary DNA to determine proportion of European ancestry, a risk factor for poor HA adaptation. Attended polysomnography was carried out over 1 night for 58 children at their resident location. Of 98 children recruited, 85 met inclusion criteria, 58 of 85 (68.2%) completed polysomnography, of which 56 were adequate for analysis: 30 at LA (17 male) and 26 at HA (16 male). There were no altitude differences in genetic ancestry, but a high proportion of European admixture (median 50.6% LA; 44.0% HA). SpO2 was less stable at HA with mean 3% and 4% oxygen desaturation indices greater (both P < 0.001) than at LA. This was not explained by periodic breathing. However, more obstructive hypopnea was observed at HA (P < 0.001), along with a trend toward more central apnea (P = 0.053); neither was explained by clinical findings. There was no difference in sleep quality between altitudes. HA native Andean children have more respiratory events when scoring relies on SpO2 desaturation due to inherent SpO2 instability. Use of American Academy of Sleep Medicine scoring criteria may yield false-positive results for obstructive sleep-disordered breathing at HA. © 2016 Associated Professional Sleep Societies, LLC.

  6. Low haemoglobin concentration in Tibetan males is associated with greater high-altitude exercise capacity.

    PubMed

    Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Wagner, P D; Ge, R L

    2015-07-15

    Tibetans living at high altitude have adapted genetically such that many display a low erythropoietic response, resulting in near sea-level haemoglobin (Hb) concentration. We hypothesized that absence of the erythropoietic response would be associated with greater exercise capacity compared to those with high [Hb] as a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to 14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak exercise (V̇O2 and V̇CO2), heart rate, cardiac output and arterial blood gas variables at peak exercise on a cycle ergometer at ∼4200 m. Lung and muscle O2 diffusional conductances were computed from these measurements. [Hb] was related (negatively) to V̇O2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1) , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = -0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2 (PaO2) or pulmonary diffusing capacity. Using multiple linear regression, variance in peak V̇O2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) = 0.88). However, variance in pulmonary gas exchange played essentially no role in determining peak V̇O2. These results (1) show higher exercise capacity in Tibetans without the erythropoietic response, supported mostly by cardiac and muscle O2 transport capacity and ventilation rather than pulmonary adaptations, and (2) support the emerging hypothesis that the polycythaemia of altitude, normally a beneficial response to low cellular PO2, may become maladaptive if excessively elevated under chronic hypoxia. The cause and effect relationships among [Hb], QT, DM, and PCO2 remain to be elucidated. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. Human Cerebral Function at High Altitude.

    DTIC Science & Technology

    1985-03-01

    increasing altitude. At the highest altitudes the % mountaineers’ behavior may be similar to an individual with a known acute organic brain syndrome (10...expedition. Only the male climbers ascended over 5,500 m. Of these, half experienced symptoms similar to an acute organic brain syndrome ; "for

  8. Metabolic characteristics and response to high altitude in Phrynocephalus erythrurus (Lacertilia: Agamidae), a lizard dwell at altitudes higher than any other living lizards in the world.

    PubMed

    Tang, Xiaolong; Xin, Ying; Wang, Huihui; Li, Weixin; Zhang, Yang; Liang, Shiwei; He, Jianzheng; Wang, Ningbo; Ma, Ming; Chen, Qiang

    2013-01-01

    Metabolic response to high altitude remains poorly explored in reptiles. In the present study, the metabolic characteristics of Phrynocephaluserythrurus (Lacertilia: Agamidae), which inhabits high altitudes (4500 m) and Phrynocephalusprzewalskii (Lacertilia: Agamidae), which inhabits low altitudes, were analysed to explore the metabolic regulatory strategies for lizards living at high-altitude environments. The results indicated that the mitochondrial respiratory rates of P. erythrurus were significantly lower than those of P. przewalskii, and that proton leak accounts for 74~79% of state 4 and 7~8% of state3 in P. erythrurus vs. 43~48% of state 4 and 24~26% of state3 in P. przewalskii. Lactate dehydrogenase (LDH) activity in P. erythrurus was lower than in P. przewalskii, indicating that at high altitude the former does not, relatively, have a greater reliance on anaerobic metabolism. A higher activity related to β-hydroxyacyl coenzyme A dehydrogenase (HOAD) and the HOAD/citrate synthase (CS) ratio suggested there was a possible higher utilization of fat in P. erythrurus. The lower expression of PGC-1α and PPAR-γ in P. erythrurus suggested their expression was not influenced by cold and low PO2 at high altitude. These distinct characteristics of P. erythrurus are considered to be necessary strategies in metabolic regulation for living at high altitude and may effectively compensate for the negative influence of cold and low PO2.

  9. Metabolic Characteristics and Response to High Altitude in Phrynocephalus erythrurus (Lacertilia: Agamidae), a Lizard Dwell at Altitudes Higher Than Any Other Living Lizards in the World

    PubMed Central

    Tang, Xiaolong; Xin, Ying; Wang, Huihui; Li, Weixin; Zhang, Yang; Liang, Shiwei; He, Jianzheng; Wang, Ningbo; Ma, Ming; Chen, Qiang

    2013-01-01

    Metabolic response to high altitude remains poorly explored in reptiles. In the present study, the metabolic characteristics of Phrynocephalus erythrurus (Lacertilia: Agamidae), which inhabits high altitudes (4500 m) and Phrynocephalus przewalskii (Lacertilia: Agamidae), which inhabits low altitudes, were analysed to explore the metabolic regulatory strategies for lizards living at high-altitude environments. The results indicated that the mitochondrial respiratory rates of P . erythrurus were significantly lower than those of P . przewalskii , and that proton leak accounts for 74~79% of state 4 and 7~8% of state3 in P . erythrurus vs. 43~48% of state 4 and 24~26% of state3 in P . przewalskii . Lactate dehydrogenase (LDH) activity in P . erythrurus was lower than in P . przewalskii , indicating that at high altitude the former does not, relatively, have a greater reliance on anaerobic metabolism. A higher activity related to β-hydroxyacyl coenzyme A dehydrogenase (HOAD) and the HOAD/citrate synthase (CS) ratio suggested there was a possible higher utilization of fat in P . erythrurus . The lower expression of PGC-1α and PPAR-γ in P . erythrurus suggested their expression was not influenced by cold and low PO2 at high altitude. These distinct characteristics of P . erythrurus are considered to be necessary strategies in metabolic regulation for living at high altitude and may effectively compensate for the negative influence of cold and low PO2. PMID:23951275

  10. The Effect of Simulated Altitude on the Visual Fields of Glaucoma Patients and the Elderly

    DTIC Science & Technology

    1991-01-01

    certification policy does not appear to put pilots or passengers with glaucoma at risk for disease progression. Under short-term exposure to mild hypoxia, we...9. Kobrick JL, Crohn E, Shukitt B, Houston CS, Sutton JR, Cymerman A. Operation Everest II: lack of an effect of extreme altitude on visual contrast

  11. Adaptation of the Long-Lived Monocarpic Perennial Saxifraga longifolia to High Altitude1[OPEN

    PubMed Central

    Morales, Melanie; Fleta-Soriano, Eva; Garcia, Maria B.

    2016-01-01

    Global change is exerting a major effect on plant communities, altering their potential capacity for adaptation. Here, we aimed at unveiling mechanisms of adaptation to high altitude in an endemic long-lived monocarpic, Saxifraga longifolia, by combining demographic and physiological approaches. Plants from three altitudes (570, 1100, and 2100 m above sea level [a.s.l.]) were investigated in terms of leaf water and pigment contents, and activation of stress defense mechanisms. The influence of plant size on physiological performance and mortality was also investigated. Levels of photoprotective molecules (α-tocopherol, carotenoids, and anthocyanins) increased in response to high altitude (1100 relative to 570 m a.s.l.), which was paralleled by reduced soil and leaf water contents and increased ABA levels. The more demanding effect of high altitude on photoprotection was, however, partly abolished at very high altitudes (2100 m a.s.l.) due to improved soil water contents, with the exception of α-tocopherol accumulation. α-Tocopherol levels increased progressively at increasing altitudes, which paralleled with reductions in lipid peroxidation, thus suggesting plants from the highest altitude effectively withstood high light stress. Furthermore, mortality of juveniles was highest at the intermediate population, suggesting that drought stress was the main environmental driver of mortality of juveniles in this rocky plant species. Population structure and vital rates in the high population evidenced lower recruitment and mortality in juveniles, activation of clonal growth, and absence of plant size-dependent mortality. We conclude that, despite S. longifolia has evolved complex mechanisms of adaptation to altitude at the cellular, whole-plant and population levels, drought events may drive increased mortality in the framework of global change. PMID:27440756

  12. Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude.

    PubMed

    Scott, Graham R; Milsom, William K

    2006-11-01

    The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.

  13. Variation in airborne 137Cs peak levels with altitude from high-altitude locations across Europe after the arrival of Fukushima-labeled air masses

    NASA Astrophysics Data System (ADS)

    Masson, Olivier; Bieringer, Jacqueline; Dalheimer, Axel; Estier, Sybille; Evrard, Olivier; Penev, Ilia; Ringer, Wolfgang; Schlosser, Clemens; Steinkopff, Thomas; Tositti, Laura; de Vismes-Ott, Anne

    2015-04-01

    During the Fukushima Daiichi nuclear power plant (FDNPP) accident, a dozen of high-altitude aerosol sampling stations, located between 850 and 3,454 m above sea level (a.s.l.), provided airborne activity levels across Europe (Fig. 1). This represents at most 5% of the total number of aerosol sampling locations that delivered airborne activity levels (at least one result) in Europe, in connection with this nuclear accident. High altitude stations are typically equipped with a high volume sampler that collects aerosols on filters. The Fukushima-labeled air mass arrival and the peak of airborne cesium-137 (137Cs) activity levels were registered in Europe at different dates depending on the location, with differences up to a factor of six on a regional scale. Besides this statement related to lowland areas, we have compared the maximum airborne levels registered at high-altitude European locations (850 m < altitudes < 3450 m) with what was observed at the closest lowland location. The vertical distribution of 137Cs peak level was not uniform even after a long travel time/distance from Japan. This being true at least in the atmospheric boundary layer and in the lower free troposphere. Moreover the relation '137Csmax vs. altitude' shows a decreasing trend (Fig. 2). Results and discussion : Comparison of 137Cs and 7Be levels shows simultaneous increases at least when the 137Cs airborne level rose for the first time (Fig. 3). Zugspitze and Jungfraujoch stations attest of a time shift between 7Be and 137Cs peak that can be due to the particular dynamic of air movements at such high altitudes. After the 137Cs peak value, the plume concentration decreased whatever the 7Be level. Due to the cosmogenic origin of 7Be, its increase in the ground-level air is usually associated with downwind air movements, i.e. stratospheric air intrusions or at least air from high-tropospheric levels, into lower atmospheric layers. This means that Fukushima-labeled air masses registered at ground

  14. Coca: High Altitude Remedy of the Ancient Incas.

    PubMed

    Biondich, Amy Sue; Joslin, Jeremy D

    2015-12-01

    The use of coca leaf for medicinal purposes is a centuries-old tradition of the native peoples of South America. Coca products are thought by many laypersons to provide risk-free benefits to users participating in strenuous activities at high altitude. Physiologic studies of coca have increased understanding of its possible mechanism of action as well as its potential impact on high altitude activities. This present work explores the role of coca throughout the history of the Andean peoples and explores whether this ancient remedy has a place in modern medicine. A focused summary of research articles with particular relevance to the field of wilderness medicine is also included to better provide the reader with lessons not only from history but also from another culture. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  15. White Mountain Research Station: 25 years of high-altitude research. [organization and functions of test facility for high altitude research

    NASA Technical Reports Server (NTRS)

    Pace, N.

    1973-01-01

    The organization and functions of a test facility for conducting research projects at high altitudes are discussed. The projects conducted at the facility include the following: (1) bird physiology, (2) cardiorespiratory physiology, (3) endocrinological studies, (4) neurological studies, (5) metabolic studies, and (6) geological studies.

  16. High-Altitude Aircraft-Based Electric-Field Measurements Above Thunderstorms

    NASA Technical Reports Server (NTRS)

    Bateman, M. G.; Blakeslee, R. J.; Bailey, J. C.; Stewart, M. F.; Blair, A. K.

    1999-01-01

    We have developed a new set of eight electric field mills that were flown on a NASA ER-2 high-altitude aircraft. During the Third Convection And Moisture EXperiment (CAMEX-3; Fall, 1998), measurements of electric field, storm dynamics, and ice microphysics were made over several hurricanes. Concurrently, the TExas-FLorida UNderflights (TEFLUN) program was being conducted to make the same measurements over Gulf Coast thunderstorms. Sample measurements are shown: typical flight altitude is 20km. Our new mills have an internal 16-bit A/D, with a resolution of 0.25V/m per bit at high gain, with a noise level less than the least significant bit. A second, lower gain channel gives us the ability to measure fields as high as 150 kV/m.

  17. Altitude-related cough

    PubMed Central

    2013-01-01

    Altitude-related cough is a troublesome condition of uncertain aetiology that affects many visitors to high altitude. The traditionally held belief that it was due solely to the inspiration of cold, dry air was refuted by observations and experiments in long duration hypobaric chamber studies. It is likely that altitude-related cough is a symptom of a number of possible perturbations in the cough reflex arc that may exist independently or together. These include loss of water from the respiratory tract; respiratory tract infections and sub-clinical high altitude pulmonary oedema. The published work on altitude-related cough is reviewed and possible aetiologies for the condition are discussed. PMID:24175933

  18. Hypoxia and Its Acid-Base Consequences: From Mountains to Malignancy.

    PubMed

    Swenson, Erik R

    Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many responses to hypoxia at both non-genomic and genomic levels, in part via altered hypoxia-inducible factor (HIF) metabolism. Healthy people at high altitude and persons hyperventilating to non-hypoxic stimuli can become alkalotic and alkalemic with arterial pH acutely rising as high as 7.7. Hypoxia-mediated respiratory alkalosis reduces sympathetic tone, blunts hypoxic pulmonary vasoconstriction and hypoxic cerebral vasodilation, and increases hemoglobin oxygen affinity. These effects and others can be salutary or counterproductive to tissue oxygen delivery and utilization, based upon magnitude of each effect and summation. With severe hypoxia either in the setting of profound arterial hemoglobin desaturation and reduced O2 content or poor perfusion (ischemia) at the global or local level, metabolic and hypercapnic acidosis develop along with considerable lactate formation and pH falling to below 6.8. Although conventionally considered to be injurious and deleterious to cell function and survival, both acidoses may be cytoprotective by various anti-inflammatory, antioxidant, and anti-apoptotic mechanisms which limit total hypoxic or ischemic-reperfusion injury. Attempts to correct acidosis by giving bicarbonate or other alkaline agents under these circumstances ahead of or concurrent with reoxygenation efforts may be ill advised. Better understanding of this so-called "pH paradox" or permissive acidosis may offer therapeutic possibilities. Rapidly growing cancers often outstrip their vascular supply compromising both oxygen and nutrient delivery and metabolic waste disposal, thus limiting their growth and metastatic potential. However, their excessive glycolysis and lactate formation may not necessarily represent oxygen insufficiency, but rather the Warburg effect-an attempt to provide a large amount

  19. Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring.

    PubMed

    Walton, Sarah L; Singh, Reetu R; Tan, Tiffany; Paravicini, Tamara M; Moritz, Karen M

    2016-03-01

    Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  20. Preliminary investigation for effects of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin system on regulation of high-altitude acclimatization.

    PubMed

    Liu, Yong-Nian; Ma, Qi-Sheng; Wu, Qiong

    2017-05-01

    This study aims to investigate the mechanism of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin (POMC) system in the regulation of high-altitude acclimatization. SD rats (male) were divided into two groups and separately fed at the 2260m and 4700m altitude. Tow groups contained 5 small groups separately, including 1 d, 3 d, 7 d, 15 d and 30 d, and 8 rats in each group. Blood, cerebrospinal fluid and tissues were taken at setting time. Leptin and Ghrelin were detected by using radioactivity immuno-assay. RNA expression of NPY and POMC were detected by using RT-PCR assay. The number of NPY positive neurons was detected by using immunofluorescence (IF) and cell counting. Other rats were sent to the 4300m and fed in animal room with regular diet and drinking. The results indicated that after being sent to high altitude region, Leptin levels at the 3rd and 7th day were significantly higher than the 1st day, while decreased at 15th, and the level at 30th day was closed to the 1st day. Ghrelin levels decreased at the 3rd, 7th and 15th day, and were lower at the 30th day. Comparing to the 1st day, NPY transcription levels increased at the 7th day, while decreased at the 30th. POMC transcription level decreased at the 7th day, while increased at the 30th gradually. The feeding of the rats fed at the 4300m decreased at the 3rd and the 5th, while increased at the 7th, 15th and 30th day. The weight of the rats changed as the feeding changing. In conclusion, after being sent to the high region, the rats were adaptive to the hypoxia environment gradually, and the steady of neuro-endocrine regulation recovered or established. Copyright © 2017. Published by Elsevier Masson SAS.

  1. High Altitude Bird Migration at Temperate Latitudes: A Synoptic Perspective on Wind Assistance

    PubMed Central

    Dokter, Adriaan M.; Shamoun-Baranes, Judy; Kemp, Michael U.; Tijm, Sander; Holleman, Iwan

    2013-01-01

    At temperate latitudes the synoptic patterns of bird migration are strongly structured by the presence of cyclones and anticyclones, both in the horizontal and altitudinal dimensions. In certain synoptic conditions, birds may efficiently cross regions with opposing surface wind by choosing a higher flight altitude with more favourable wind. We observed migratory passerines at mid-latitudes that selected high altitude wind optima on particular nights, leading to the formation of structured migration layers at varying altitude up to 3 km. Using long-term vertical profiling of bird migration by C-band Doppler radar in the Netherlands, we find that such migration layers occur nearly exclusively during spring migration in the presence of a high-pressure system. A conceptual analytic framework providing insight into the synoptic patterns of wind assistance for migrants that includes the altitudinal dimension has so far been lacking. We present a simple model for a baroclinic atmosphere that relates vertical profiles of wind assistance to the pressure and temperature patterns occurring at temperate latitudes. We show how the magnitude and direction of the large scale horizontal temperature gradient affects the relative gain in wind assistance that migrants obtain through ascending. Temperature gradients typical for northerly high-pressure systems in spring are shown to cause high altitude wind optima in the easterly sectors of anticyclones, thereby explaining the frequent observations of high altitude migration in these synoptic conditions. Given the recurring synoptic arrangements of pressure systems across temperate continents, the opportunities for exploiting high altitude wind will differ between flyways, for example between easterly and westerly oceanic coasts. PMID:23300969

  2. High altitude bird migration at temperate latitudes: a synoptic perspective on wind assistance.

    PubMed

    Dokter, Adriaan M; Shamoun-Baranes, Judy; Kemp, Michael U; Tijm, Sander; Holleman, Iwan

    2013-01-01

    At temperate latitudes the synoptic patterns of bird migration are strongly structured by the presence of cyclones and anticyclones, both in the horizontal and altitudinal dimensions. In certain synoptic conditions, birds may efficiently cross regions with opposing surface wind by choosing a higher flight altitude with more favourable wind. We observed migratory passerines at mid-latitudes that selected high altitude wind optima on particular nights, leading to the formation of structured migration layers at varying altitude up to 3 km. Using long-term vertical profiling of bird migration by C-band Doppler radar in the Netherlands, we find that such migration layers occur nearly exclusively during spring migration in the presence of a high-pressure system. A conceptual analytic framework providing insight into the synoptic patterns of wind assistance for migrants that includes the altitudinal dimension has so far been lacking. We present a simple model for a baroclinic atmosphere that relates vertical profiles of wind assistance to the pressure and temperature patterns occurring at temperate latitudes. We show how the magnitude and direction of the large scale horizontal temperature gradient affects the relative gain in wind assistance that migrants obtain through ascending. Temperature gradients typical for northerly high-pressure systems in spring are shown to cause high altitude wind optima in the easterly sectors of anticyclones, thereby explaining the frequent observations of high altitude migration in these synoptic conditions. Given the recurring synoptic arrangements of pressure systems across temperate continents, the opportunities for exploiting high altitude wind will differ between flyways, for example between easterly and westerly oceanic coasts.

  3. Role of Arcuate Nucleus in the Regulation of Feeding Behavior in the Process of Altitude Acclimatization in Rats.

    PubMed

    Liu, Xiang-Wen; Yin, Jie; Ma, Qi-Sheng; Qi, Chu-Chu; Mu, Ji-Ying; Zhang, Lang; Gao, Li-Ping; Jing, Yu-Hong

    2017-09-01

    Liu, Xiang-Wen, Jie Yin, Qi-Sheng Ma, Chu-Chu Qi, Ji-Ying Mu, Lang Zhang, Li-Ping Gao, and Yu-Hong Jing. Role of arcuate nucleus in the regulation of feeding behavior in the process of altitude acclimatization in rats. High Alt Med Biol. 18:234-241, 2017.-Highly efficient energy utilization and metabolic homeostasis maintenance rely on neuromodulation. Altitude exposure is known to stimulate neuroendocrine systems to respond to acute hypoxia and adaptive acclimatization. However, limited data on how the adaptive regulation of the arcuate nucleus performs in the process of altitude acclimatization are available. In the present study, male Sprague Dawley rats were transported to Huashixia, Qinghai (with an altitude of 4400 m) from Xian (with an altitude of 300 m) by air; rats were consistently raised in Xian as control. Food uptake and body weight were measured consecutively after being subjected to high-altitude condition. Contents of plasma leptin and ghrelin were analyzed by the Enzyme Linked Immunosorbent Assay (ELISA) Kits. Brain coronal sections were obtained, and neuropeptide Y (NPY), proopiomelanocotin (POMC), and c-fos immunoreactivity in arcuate nucleus were observed. Arcuate nucleus was isolated from the hypothalamus, and the mRNA of NPY and POMC were measured by quantitative real-time polymerase chain reaction. Our results showed both food consumption and body weight decreased in the high plateau compared with rats raised in the low-altitude condition. Plasma leptin increased at the early stage, and ghrelin decreased at a later stage after reaching the high plateau. The peak of c-fos immunoreactivity in the arcuate nucleus was at day 3 after reaching the high plateau. The expression level of NPY increased, and POMC decreased in the arcuate nucleus at day 7 after reaching the high plateau compared with the plain control group. These results indicate that the arcuate nucleus of hypothalamus performs an important function in regulating feeding behavior

  4. Nonequilibrium viscous flow over Jovian entry probes at high altitudes

    NASA Technical Reports Server (NTRS)

    Kumar, A.; Szema, K. Y.; Tiwari, S. N.

    1979-01-01

    The viscous chemical nonequilibrium flow around a Jovian entry body is investigated at high altitudes using two different methods. First method is only for the stagnation region and integrates the full Navier-Stokes equations from the body surface to the freestream. The second method uses viscous shock layer equations between the body surface and the shock. Due to low Reynolds numbers, both methods use surface slip boundary conditions and the second method also uses shock slip boundary conditions. The results of the two methods are compared at the stagnation point. It is found that the entire shock layer is under chemical nonequilibrium at higher altitudes and that the slip boundary conditions are important at these altitudes.

  5. Solar Cell Short Circuit Current Errors and Uncertainties During High Altitude Calibrations

    NASA Technical Reports Server (NTRS)

    Snyder, David D.

    2012-01-01

    High altitude balloon based facilities can make solar cell calibration measurements above 99.5% of the atmosphere to use for adjusting laboratory solar simulators. While close to on-orbit illumination, the small attenuation to the spectra may result in under measurements of solar cell parameters. Variations of stratospheric weather, may produce flight-to-flight measurement variations. To support the NSCAP effort, this work quantifies some of the effects on solar cell short circuit current (Isc) measurements on triple junction sub-cells. This work looks at several types of high altitude methods, direct high altitude meas urements near 120 kft, and lower stratospheric Langley plots from aircraft. It also looks at Langley extrapolation from altitudes above most of the ozone, for potential small balloon payloads. A convolution of the sub-cell spectral response with the standard solar spectrum modified by several absorption processes is used to determine the relative change from AMO, lscllsc(AMO). Rayleigh scattering, molecular scatterin g from uniformly mixed gases, Ozone, and water vapor, are included in this analysis. A range of atmosph eric pressures are examined, from 0. 05 to 0.25 Atm to cover the range of atmospheric altitudes where solar cell calibrations a reperformed. Generally these errors and uncertainties are less than 0.2%

  6. Fetal in vivo continuous cardiovascular function during chronic hypoxia

    PubMed Central

    Allison, B. J.; Brain, K. L.; Niu, Y.; Kane, A. D.; Herrera, E. A.; Thakor, A. S.; Botting, K. J.; Cross, C. M.; Itani, N.; Skeffington, K. L.; Beck, C.

    2016-01-01

    Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism. Abstract Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean PaO2 levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery

  7. Lockheed ER-2 high altitude research aircraft

    NASA Image and Video Library

    1997-11-04

    ER-2 tail number 706, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  8. The evolution of Titan's high-altitude aerosols under ultraviolet irradiation

    NASA Astrophysics Data System (ADS)

    Carrasco, Nathalie; Tigrine, Sarah; Gavilan, Lisseth; Nahon, Laurent; Gudipati, Murthy S.

    2018-04-01

    The Cassini-Huygens space mission revealed that Titan's thick brownish haze is initiated high in the atmosphere at an altitude of about 1,000 km, before a slow transportation down to the surface. Close to the surface, at altitudes below 130 km, the Huygens probe provided information on the chemical composition of the haze. So far, we have not had insights into the possible photochemical evolution of the aerosols making up the haze during their descent. Here, we address this atmospheric aerosol aging process, simulating in the laboratory how solar vacuum ultraviolet irradiation affects the aerosol optical properties as probed by infrared spectroscopy. An important evolution was found that could explain the apparent contradiction between the nitrogen-poor infrared spectroscopic signature observed by Cassini below 600 km of altitude in Titan's atmosphere and a high nitrogen content as measured by the aerosol collector and pyrolyser of the Huygens probe at the surface of Titan.

  9. The evolution of Titan's high-altitude aerosols under ultraviolet irradiation

    NASA Astrophysics Data System (ADS)

    Carrasco, Nathalie; Tigrine, Sarah; Gavilan, Lisseth; Nahon, Laurent; Gudipati, Murthy S.

    2018-06-01

    The Cassini-Huygens space mission revealed that Titan's thick brownish haze is initiated high in the atmosphere at an altitude of about 1,000 km, before a slow transportation down to the surface. Close to the surface, at altitudes below 130 km, the Huygens probe provided information on the chemical composition of the haze. So far, we have not had insights into the possible photochemical evolution of the aerosols making up the haze during their descent. Here, we address this atmospheric aerosol aging process, simulating in the laboratory how solar vacuum ultraviolet irradiation affects the aerosol optical properties as probed by infrared spectroscopy. An important evolution was found that could explain the apparent contradiction between the nitrogen-poor infrared spectroscopic signature observed by Cassini below 600 km of altitude in Titan's atmosphere and a high nitrogen content as measured by the aerosol collector and pyrolyser of the Huygens probe at the surface of Titan.

  10. Applications of a high-altitude powered platform /HAPP/

    NASA Technical Reports Server (NTRS)

    Kuhner, M. B.

    1979-01-01

    The high-altitude powered platform (HAPP) is a conceptual unmanned vehicle which could be either an airship or airplane. It would keep station at an altitude of 70,000 ft above a fixed point on the ground. A microwave power transmission system would beam energy from the ground up to the HAPP to power an electric motor-driven propeller and the payload. A study of the HAPP has shown that it could potentially be a cost-competitive platform for such remote sensing applications as forest fire detection, Great Lakes ice monitoring and Coast Guard law enforcement. It also has significant potential as a communications relay platform for (among other things) direct broadcast to home TVs over a large region.

  11. Hematological parameters in high altitude residents living at 4,355, 4,660, and 5,500 meters above sea level.

    PubMed

    León-Velarde, F; Gamboa, A; Chuquiza, J A; Esteba, W A; Rivera-Chira, M; Monge, C C

    2000-01-01

    There have been a number of reports describing the hematological indicators of Andean residents living at altitudes above 4,000 m, but several confounding factors have made the published results difficult to interpret. To clear up the effect of hypoxia on hemoglobin concentration (Hb, g/dL), hematocrit (Hct, %) and red blood cell concentration (RBC, cells/microL), this publication describes and analyzes these variables in children, men, and women from three large and homogeneous populations living at 4,355 m (n = 151), 4,660 m (n = 400), and 5,500 m (n = 273) in the Southern Peruvian Andes. Hb, Hct, and RBC increase with age in men (p < 0.001), as well as in women (p < 0.001) at the three altitudes of the study. In children (boys and girls) living at 5,500, Hb increases 11% when compared with children living at 4,355 m, and in adults, Hb increases 9.6% when comparing the same altitudes. The maximum percentage increase in Hb with age was 5.6% at 5,500 m, in men and 3.2% at 4,355 m, in women. The average percentage of difference for the Hb concentration between adult men and women is 6.6% at 4,355 m, 9.8% at 4,660 m, and 11.6% at 5,500 m. The differences in Hb concentration between men and women can only be seen after puberty. Finally, Hb is higher in older than younger women, which confirms the role of menopause in the development of erythremia. The result of this analysis reinforces the notion that Hb and Hct seem to be stable and useful parameters for acclimatization only at moderate altitudes; with aging or with increasing altitude, they may become excessive and lose their efficiency to protect the venous oxygen pressure.

  12. [Hemoglobin changes (Hb) in miners exposed to high altitude and associated factors].

    PubMed

    Mejia, Christian R; Quiñones-Laveriano, Dante M; Gomero, Raúl; Pérez-Pérez, Luis

    To determine the variation of hemoglobin (Hb) in two groups of miners working at different altitudes. A longitudinal study conducted in a private company. Hb was obtained from entrance exams and annual checks of workers at two locations: at sea level and at Peruvian highlands (4,100 m), taken by trained staff and equipment calibrated to environmental conditions. We analyzed variations in the course of the years with the PA-GEE statistical test; p values were obtained. Of the 376 workers, 89% (322) were men, the median age was 32 years (range 20-57) and 84% (304) were at high altitude. In multivariate analysis, male sex (p < 0.001), body mass index (BMI; p = 0.021) and working at high altitude (p < 0.001) were associated with the greatest variation of Hb in time, adjusted for age, length, and type of work. These findings should be considered for health surveillance of workers exposed to similar conditions to prevent chronic mountain sickness. The change in Hb of miners was associated with male sex, BMI, and work at high altitude.

  13. High altitude flights by ruddy shelduck Tadorna ferruginea during trans-Himalayan migrations

    USGS Publications Warehouse

    Parr, N.; Bearhop, S.; Douglas, David C.; Takekawa, J.Y.; Prosser, Diann J.; Newman, S.H.; Perry, W.M.; Balachandran, S.; Witt, M.J.; Hou, Y.; Luo, Z.; Hawkes, L.A.

    2017-01-01

    Birds that migrate across high altitude mountain ranges are faced with the challenge of maintaining vigorous exercise in environments with limited oxygen. Ruddy shelducks are known to use wintering grounds south of the Tibetan Plateau at sea level and breeding grounds north of Himalayan mountain range. Therefore, it is likely these shelducks are preforming high altitude migrations. In this study we analyse satellite telemetry data collected from 15 ruddy shelduck from two populations wintering south of the Tibetan Plateau from 2007 to 2011. During north and south migrations ruddy shelduck travelled 1481 km (range 548–2671 km) and 1238 km (range 548–2689 km) respectively. We find mean maximum altitudes of birds in flight reached 5590 m (range of means 4755–6800 m) and mean maximum climb rates of 0.45 m s–1 (range 0.23–0.74 m s–1). The ruddy shelduck is therefore an extreme high altitude migrant that has likely evolved a range of physiological adaptations in order to complete their migrations.

  14. AltitudeOmics: enhanced cerebrovascular reactivity and ventilatory response to CO2 with high-altitude acclimatization and reexposure.

    PubMed

    Fan, Jui-Lin; Subudhi, Andrew W; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Lovering, Andrew T; Roach, Robert C

    2014-04-01

    The present study is the first to examine the effect of high-altitude acclimatization and reexposure on the responses of cerebral blood flow and ventilation to CO2. We also compared the steady-state estimates of these parameters during acclimatization with the modified rebreathing method. We assessed changes in steady-state responses of middle cerebral artery velocity (MCAv), cerebrovascular conductance index (CVCi), and ventilation (V(E)) to varied levels of CO2 in 21 lowlanders (9 women; 21 ± 1 years of age) at sea level (SL), during initial exposure to 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon reexposure to altitude following either 7 (POST7) or 21 days (POST21) at low altitude (1,525 m). In the nonacclimatized state (ALT1), MCAv and V(E) responses to CO2 were elevated compared with those at SL (by 79 ± 75% and 14.8 ± 12.3 l/min, respectively; P = 0.004 and P = 0.011). Acclimatization at ALT16 further elevated both MCAv and Ve responses to CO2 compared with ALT1 (by 89 ± 70% and 48.3 ± 32.0 l/min, respectively; P < 0.001). The acclimatization gained for V(E) responses to CO2 at ALT16 was retained by 38% upon reexposure to altitude at POST7 (P = 0.004 vs. ALT1), whereas no retention was observed for the MCAv responses (P > 0.05). We found good agreement between steady-state and modified rebreathing estimates of MCAv and V(E) responses to CO2 across all three time points (P < 0.001, pooled data). Regardless of the method of assessment, altitude acclimatization elevates both the cerebrovascular and ventilatory responsiveness to CO2. Our data further demonstrate that this enhanced ventilatory CO2 response is partly retained after 7 days at low altitude.

  15. Right heart function during simulated altitude in patients with pulmonary arterial hypertension

    PubMed Central

    Seccombe, Leigh M; Chow, Vincent; Zhao, Wei; Lau, Edmund M T; Rogers, Peter G; Ng, Austin C C; Veitch, Elizabeth M; Peters, Matthew J; Kritharides, Leonard

    2017-01-01

    Objective Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Methods Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. Results The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Conclusions Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function. PMID:28123765

  16. Perseus High Altitude Remotely Piloted Aircraft on Ramp

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Perseus proof-of-concept vehicle waits on Rogers Dry Lake in the pre-dawn darkness before a test flight at the Dryden Flight Research Center, Edwards, California. Perseus B is a remotely piloted aircraft developed as a design-performance testbed under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project. Perseus is one of several flight vehicles involved in the ERAST project. A piston engine, propeller-powered aircraft, Perseus was designed and built by Aurora Flight Sciences Corporation, Manassas, Virginia. The objectives of Perseus B's ERAST flight tests have been to reach and maintain horizontal flight above altitudes of 60,000 feet and demonstrate the capability to fly missions lasting from 8 to 24 hours, depending on payload and altitude requirements. The Perseus B aircraft established an unofficial altitude record for a single-engine, propeller-driven, remotely piloted aircraft on June 27, 1998. It reached an altitude of 60,280 feet. In 1999, several modifications were made to the Perseus aircraft including engine, avionics, and flight-control-system improvements. These improvements were evaluated in a series of operational readiness and test missions at the Dryden Flight Research Center, Edwards, California. Perseus is a high-wing monoplane with a conventional tail design. Its narrow, straight, high-aspect-ratio wing is mounted atop the fuselage. The aircraft is pusher-designed with the propeller mounted in the rear. This design allows for interchangeable scientific-instrument payloads to be placed in the forward fuselage. The design also allows for unobstructed airflow to the sensors and other devices mounted in the payload compartment. The Perseus B that underwent test and development in 1999 was the third generation of the Perseus design, which began with the Perseus Proof-Of-Concept aircraft. Perseus was initially developed as part of NASA's Small High-Altitude Science Aircraft (SHASA) program, which later evolved into the

  17. An anxiety, personality and altitude symptomatology study during a 31-day period of hypoxia in a hypobaric chamber (experiment 'Everest-Comex 1997').

    PubMed

    Nicolas, M; Thullier-Lestienne, F; Bouquet, C; Gardette, B; Gortan, C; Joulia, F; Bonnon, M; Richalet, J P; Therme, P; Abraini, J H

    1999-12-01

    Extreme environmental situations are useful tools for the investigation of the general processes of adaptation. Among such situations, high altitude of more than 3000 m produces a set of pathological disorders that includes both cerebral (cAS) and respiratory (RAS) altitude symptoms. High altitude exposure further induces anxiety responses and behavioural disturbances. The authors report an investigation on anxiety responses, personality traits, and altitude symptoms (AS) in climbers participating in a 31-day period of confinement and gradual decompression in a hypobaric chamber equivalent to a climb from sea-level to Mount Everest (8848 m altitude). Personality traits, state-trait anxiety, and AS were assessed, using the Cattell 16 Personality Factor questionnaire (16PF), the Spielberger's State-Trait Anxiety Inventory (STAI), and the Lake Louise concensus questionnaire. Results show significant group effect for state-anxiety and AS; state-anxiety and AS increased as altitude increased. They also show that state-type anxiety shows a similar time-course to cAS, but not RAS. Alternatively, our results demonstrate a significant negative correlation between Factor M of the 16PF questionnaire, which is a personality trait that ranges from praxernia to autia. In contrast, no significant correlation was found between personality traits and AS. This suggests that AS could not be predicted using personality traits and further support that personality traits, such as praxernia (happening sensitivity), could play a major role in the occurrence of state-type anxiety responses in extreme environments. In addition, the general processes of coping and adaptation in individuals participating in extreme environmental experiments are discussed.

  18. Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude.

    PubMed

    Hu, S L; Hu, R; Li, F; Liu, Z; Xia, Y Z; Cui, G Y; Feng, H

    2008-01-01

    Recent studies have shown that preconditioning with hyperbaric oxygen (HBO) can reduce ischemic and hemorrhagic brain injury. We investigated effects of HBO preconditioning on traumatic brain injury (TBI) at high altitude and examined the role of matrix metalloproteinase-9 (MMP-9) in such protection. Rats were randomly divided into 3 groups: HBO preconditioning group (HBOP; n = 13), high-altitude group (HA; n = 13), and high-altitude sham operation group (HASO; n = 13). All groups were subjected to head trauma by weight-drop device, except for HASO group. HBOP rats received 5 sessions of HBO preconditioning (2.5 ATA, 100% oxygen, 1 h daily) and then were kept in hypobaric chamber at 0.6 ATA (to simulate pressure at 4000m altitude) for 3 days before operation. HA rats received control pretreatment (1 ATA, room air, 1 h daily), then followed the same procedures as HBOP group. HASO rats were subjected to skull opening only without brain injury. Twenty-four hours after TBI, 7 rats from each group were examined for neurological function and brain water content; 6 rats from each group were killed for analysis by H&E staining and immunohistochemistry. Neurological outcome in HBOP group (0.71 +/- 0.49) was better than HA group (1.57 +/- 0.53; p < 0.05). Preconditioning with HBO significantly reduced percentage of brain water content (86.24 +/- 0.52 vs. 84.60 +/- 0.37; p < 0.01). Brain morphology and structure seen by light microscopy was diminished in HA group, while fewer pathological injuries occurred in HBOP group. Compared to HA group, pretreatment with HBO significantly reduced the number of MMP-9-positive cells (92.25 +/- 8.85 vs. 74.42 +/- 6.27; p < 0.01). HBO preconditioning attenuates TBI in rats at high altitude. Decline in MMP-9 expression may contribute to HBO preconditioning-induced protection of brain tissue against TBI.

  19. [Analysis of violent deaths of mountaineers and tourists at high altitudes].

    PubMed

    Pigolkin, Iu I; Mechukaev, A A; Mechukaev, A M

    2012-01-01

    The principal causes of violent death of mountaineers and tourists at high altitudes are described with special reference to the character of injuries to the skin, soft tissues, bones, and internal organs inflicted by mechanical impacts. The cases of violent death from other factors are described, such as general hypothermia, atmospheric electricity, compression and obturation asphyxia of mountaineers and tourists who died in the epicenter of an avalanche. The additional criteria for forensic medical diagnostics of violent death of montaineers and tourists at high altitudes are considered.

  20. Systems Design and Experimental Evaluation of a High-Altitude Relight Test Facility

    NASA Astrophysics Data System (ADS)

    Paxton, Brendan

    Novel advances in gas turbine engine combustor technology, led by endeavors into fuel efficiency and demanding environmental regulations, have been fraught with performance and safety concerns. While the majority of low emissions gas turbine engine combustor technology has been necessary for power generation applications, the push for ultra-low NOx combustion in aircraft jet engines has been ever present. Recent state-of-the-art combustor designs notably tackle historic emissions challenges by operating at fuel-lean conditions, which are characterized by an increase in the amount of air flow sent to the primary combustion zone. While beneficial in reducing NOx emissions, the fuel-lean mechanisms that characterize these combustor designs rely heavily upon high-energy and high-velocity air flows to sufficiently mix and atomize fuel droplets, ultimately leading to flame stability concerns during low-power operation. When operating at high-altitude conditions, these issues are further exacerbated by the presence of low ambient air pressures and temperatures, which can lead to engine flame-out situations and hamper engine relight attempts. To aid academic and industrial research ventures into improving the high-altitude lean blow-out and relight performance of modern gas turbine engine combustor technologies, the High-Altitude Relight Test Facility (HARTF) was designed and constructed at the University of Cincinnati (UC) Combustion and Fire Research Laboratory (CFRL). Following its construction, an experimental evaluation of its abilities to facilitate optically-accessible ignition, combustion, and spray testing for gas turbine engine combustor hardware at simulated high-altitude conditions was performed. In its evaluation, performance limit references were established through testing of the HARTF vacuum and cryogenic air-chilling capabilities. These tests were conducted with regard to end-user control---the creation and the maintenance of a realistic high-altitude