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At least 37 records · Page 2

Effects on Task Performance and Psychophysiological Measures of Performance During Normobaric Hypoxia Exposure

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 to the current knowledge of psychophysiologically-based input to automation to increase aviation safety.

Stephens, Chad↗

Adaptation of metabolism to multicellular aggregation, hypoxia and obese stromal cell incorporation as potential measure of survival of ovarian metastases

Ovarian metastases exfoliate from the primary tumor and it is thought that aggregation supports their survival in the peritoneal cavity during dissemination but the underlying mechanisms are not clearly identified. We have previously shown that ovarian cancer cells acquire an increasingly glycolytic and metabolic flexible phenotype during progression. In the present study, we investigated how hypoxia, aggregation, and the incorporation of the obese stromal vascular fraction (SVF) affect cellular metabolism and the response to common anti-cancer and anti-diabetic drugs. Our results show a reduction of glucose uptake, lactate secretion, cellular respiration and ATP synthesis in response to hypoxia and aggregation, suggesting that the observed reduced proliferation of cells aggregated into spheroids is the result of a down-regulation of respiration. Recruitment of SVF to spheroids increased the spheroids invasive capacity but reduced respiration only in the most aggressive cells. Further, aggregation and hypoxia reduced the response to the metabolic drugs AICAR and metformin, and the chemotherapeutic agents cisplatin and paclitaxel. Our results suggest that the adaptation of cellular metabolism may contribute to enhanced survival under non-permissive conditions, and that these metabolic alterations may provide targets for future interventions that aim to enhance the survival of women with metastatic ovarian cancer.

60 APPLIED LIFE SCIENCES↗

U2AF - Hypoxia-induced fas alternative splicing regulator

The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt to altered cellular conditions. Hypoxia also plays a key role in the pathophysiology of many disease states. Recent studies have revealed that tumorigenesis and hypoxia are involved in large-scale alterations in alternative pre-mRNA splicing. Fas pre-mRNA is alternatively spliced by excluding exon 6 to produce soluble Fas (sFas) protein that lacks a transmembrane domain and acts by inhibiting Fas mediated apoptosis. }In the present study we show that U2AF is involved in hypoxia dependent anti-apoptotic Fas mRNA isoform formation. Our performed studies show that U2AF-RNA interaction is reduced in hypoxic cells, leading to reduction of Fas and increased sFas mRNAs formation. Efficient U2AF-RNA interactions of both subunits are important for Fas exon 6 inclusion into forming mRNA in normoxic and hypoxic cells.

60 APPLIED LIFE SCIENCES↗

Response of hypoxia to future climate change is sensitive to methodological assumptions

Climate-induced changes in hypoxia are among the most serious threats facing estuaries, which are among the most productive ecosystems on Earth. Future projections of estuarine hypoxia typically involve long-term multi-decadal continuous simulations or more computationally efficient time slice and delta methods that are restricted to short historical and future periods. We make a first comparison of these three methods by applying a linked terrestrial–estuarine model to the Chesapeake Bay, a large coastal-plain estuary in the eastern United States. Results show that the time slice approach accurately captures the behavior of the continuous approach, indicating a minimal impact of model memory. However, increases in mean annual hypoxic volume by the mid-twenty-first century simulated by the delta approach (+ 19%) are approximately twice as large as the time slice and continuous experiments (+ 9% and + 11%, respectively), indicating an important impact of changes in climate variability. Our findings suggest that system memory and projected changes in climate variability, as well as simulation length and natural variability of system hypoxia, should be considered when deciding to apply the more computationally efficient delta and time slice methods.

54 ENVIRONMENTAL SCIENCES↗

Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males

Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders ( n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([ 13 C]glucose and [6,6- 2 H 2 ]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower ( P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA ( P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate ( r = -0.738) and Δγ-glutamylalanine ( r = -0.810), were inversely associated ( P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate ( r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate ( r = -0.738) were inversely associated ( P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.

59 BASIC BIOLOGICAL SCIENCES↗

Cardiac beta-adrenergic receptors and coronary hemodynamics in the conscious dog during hypoxic hypoxia.

The mechanisms by which acute hypoxia (10% and 5% oxygen) mediates changes in coronary blood flow and cardiac function were investigated in the conscious dog. When the dogs breathed hypoxic gas mixtures through a tracheostomy, both arterial and coronary sinus oxygen tensions were significantly decreased. With 5% oxygen, there were significant increases in heart rate (25%), maximum left ventricular dP/dt (39%), left circumflex coronary artery blood flow (163%), and left ventricular oxygen consumption (52%), which were attenuated by beta-adrenergic blockage with propranolol. When electrical pacing was used to keep the ventricular rate constant during hypoxia, there was no significant difference in coronary blood flow before and after beta blockade. Beta-adrenergic receptor activity in the myocardium participates in the integrated response to hypoxia although it may not cause active vasodilation of the coronary vessels.

Erickson, H. H.↗

Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

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.

Erickson, H. H.↗

Lymphoidal involution and delayed homograft rejection in hypoxia-exposed mice.

Investigation of the relationship between histologic and cytochemical response patterns of the thymus, spleen, and lymph nodes of mice exposed to moderate hypoxia (380 mm Hg), and study, by histologic analysis, of the effect of hypoxia exposure on the skin homograft reaction used as an index of immunologic potential. The results obtained include the finding that functional changes in lymphatic organs occur during early weeks of hypoxia acclimation and that these changes probably reduce the ability of an animal to react to an immunological challenge.

Kmetz, J. M.↗

Hypoxia, an adjunct in helium-cold hypothermia - Sparing effect on hepatic and cardiac metabolites.

Investigation of the effect of hypoxia on the depletion of metabolites that occurs in helium-aided induction of hypothermia. Hypoxic slowing of the heart of a hamster while exposed to cold helox is demonstrated. An attempt is made to evaluate the relative importance of cardiac slowing and limitation of thermogenesis in determining the effect of hypoxia. In explanation of the results presented, it is suggested that hypoxia limits the energy expenditure by the heart during induction.

Anderson, G. L.↗

Tolerance of acute hypoxia while performing operator activity and after a prolonged period under altered gas environment conditions

Human and animal studies on physiological factors in resistance to acute hypoxia are elaborated. Results show that tolerance of acute hypoxia depends on gas composition and temperature in a sealed cabin, on the length of the stay and motive regime, and on the kind of operator and professional activity. After preliminary adaptation to hypoxia, resistance of the body increases not only to insufficiency of oxygen in inspired air, but also to the effects of other extremum factors of manned space flight.

Bloshchinskiy, P.↗

Topochemical differences in the amount of RNA in the motoneurons of the spinal chord in hypoxia and hypokinesia

Reactions to hypoxia and hypoknesia were compared by measuring charges in the amount of ribonucleic acid (RNA) in the cytoplasm of neurons of the intumescentia cervicalis and lumbalis. Animals were subjected to hypoxia, hypokinesia and both combined and a control group to neither. A total of two groups of motoneurons were compared, one innervating the respiratory musculature, the other the musculature of the lower extremities, so that hypoxic hypoxia would probably affect the first group primarily and hypokinesia the second. Results indicate that neither affect the amount of RNA in the neurons of the first group but a significant increase is noted in neurons of the second group. Other significant results are reported.

Brumberg, V. A.↗

Modulation of human sinus node function by systemic hypoxia

The present study was conducted to determine whether bradycardia develops during systemic hypoxia in supine conscious human volunteers when respiratory frequency and tidal volume are maintained at constant levels. The obtained results suggest that mild hypoxia provokes cardioacceleration in humans, independent of changes of ventilation or baroreflex responsiveness. The earliest cardioacceleration is more prominent in the inspiratory than in the expiratory phase of respiration, and occurs with very small reductions of arterial oxygen saturation. Moderate systemic hypoxia dampens fluctuations of heart rate during the respiratory cycle.

Eckberg, D. L.↗

Investigation of the combined effects of bedrest and mild hypoxia

Subjects were exposed to an 8-h mild hypoxia exposure (8000 ft. equivalent, 2438 m) with and without a 28-h period of 6 deg headdown bedrest. Anticipated responses to the bedrest and the hypoxia were observed. There was no indication that bedrest affected the arterial oxygenation or the oxygen gradient across the lungs of the subjects undergoing mild hypoxia. It is concluded that there is no evidence that would preclude an alveolar O2 pressure as low as 69 torr during contingency spacecraft operation.

Waligora, J. M.↗

Zones of coastal hypoxia revealed by satellite scanning have implications for strategic fishing

Little is known about the spatial and temporal scales of hypoxic bottom water areas that occur along the inner continental shelf of Texas and Louisiana. Because hypoxia appears to be related to surface chlorophyll and temperature, which can both be measured with the Coastal Zone Color Scanner aboard the Nimbus 7 satellite, an attempt has been made to determine whether conditions favorable for the formation of hypoxia could be detected and monitored from space. A linear discriminant function has identified areas of bottom water hypoxia detected by research vessels up to 10 days after satellite overpass, and predicted hypoxic areas without resort to research vessel data. Such space mapping may be of consequence for marine resource management and exploitation.

Leming, T. D.↗

Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia

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.

Loeppky, J. A.↗

Evidence of root zone hypoxia in Brassica rapa L. grown in microgravity

A series of experiments was conducted aboard the U.S. space shuttle and the Mir space station to evaluate microgravity-induced root zone hypoxia in rapid-cycling Brassica (Brassica rapa L.), using both root and foliar indicators of low-oxygen stress to the root zone. Root systems from two groups of plants 15 and 30 d after planting, grown in a phenolic foam nutrient delivery system on the shuttle (STS-87), were harvested and fixed for microscopy or frozen for enzyme assays immediately postflight or following a ground-based control. Activities of fermentative enzymes were measured as indicators of root zone hypoxia and metabolism. Following 16 d of microgravity, ADH (alcohol dehydrogenase) activity was increased in the spaceflight roots 47% and 475% in the 15-d-old and 30-d-old plants, respectively, relative to the ground control. Cytochemical localization showed ADH activity in only the root tips of the space-grown plants. Shoots from plants that were grown from seed in flight in a particulate medium on the Mir station were harvested at 13 d after planting and quick-frozen and stored in flight in a gaseous nitrogen freezer or chemically fixed in flight for subsequent microscopy. When compared to material from a high-fidelity ground control, concentrations of shoot sucrose and total soluble carbohydrate were significantly greater in the spaceflight treatment according to enzymatic carbohydrate analysis. Stereological analysis of micrographs of sections from leaf and cotyledon tissue fixed in flight and compared with ground controls indicated no changes in the volume of protoplast, cell wall, and intercellular space in parenchyma cells. Within the protoplasm, the volume occupied by starch was threefold higher in the spaceflight than in the ground control, with a concomitant decrease in vacuolar volume in the spaceflight treatment. Both induction of fermentative enzyme activity in roots and accumulation of carbohydrates in foliage have been repeatedly shown to occur in response to root zone oxygen deprivation. These results indicate that root zone hypoxia is a persistent challenge in spaceflight plant growth experiments and may be caused by microgravity-induced changes in fluid and gas distribution.

long duration↗

Effects of hypoxia on sympathetic neural control in humans

This special issue is principally focused on the time domain of the adaptive mechanisms of ventilatory responses to short-term, long-term and intermittent hypoxia. The purpose of this review is to summarize the limited literature on the sympathetic neural responses to sustained or intermittent hypoxia in humans and attempt to discern the time domain of these responses and potential adaptive processes that are evoked during short and long-term exposures to hypoxia.

Review↗

A Numerical Study of Hypoxia in Chesapeake Bay Using an Unstructured Grid Model: Validation and Sensitivity to Bathymetry Representation

A three-dimensional unstructured-grid hydrodynamic and water quality model (Semi-implicit Cross-scale Hydroscience Intergrated System Model-Integrated Compartment Model) is applied successfully for Chesapeake Bay. The model is validated with observations of salinity, chlorophyll-a, dissolved oxygen, nutrients, and phytoplankton productions from the year 1991 to 1995 for the mainstem and some major tributaries, based on multiple model skill scores. Model experiments are conducted to test the importance of having (1) an accurate representation of bathymetry to correctly predict hypoxia and other processes and (2) a high-resolution model grid for tributaries to correctly simulate water quality variables. Further, comparison with the model experiment results with bathymetry smoothing indicates that bathymetry smoothing, as commonly used for many systems, changes the stratification and lateral circulation pattern, resulting in more salt intrusion into shallow water regions, and an increase in the freshwater age. Consequently, a model with bathymetry smoothing can lead to an unrealistic prediction of the distribution of hypoxia and phytoplankton production. Local grid refinement shows significant improvement of model simulations on local stratification and water quality variables. Overall, the use of high-resolution unstructured grid model leads to a faithful representation of the complex geometry, and thus a seamless cross-scale capability for simulating water quality processes in the Bay including tributaries and tidal creeks.

54 ENVIRONMENTAL SCIENCES↗