Metabolic-adaptation of the chick embryo to chronic hypoxia
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Beattie, J.↗
SEARCH · Engineering Papers
Results for “hypoxia”
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Hematologic changes in mice during and after exposure to severe hypobaric hypoxia
Exposing mice to an atmospheric pressure of 300 mm Hg for 16 d caused a variety of hematologic effects. Hematocrit increased rapidly in the first 8 d of exposure and slowly in the second 8 d. Reticulocyte counts rose above normal, peaked on day 8, and then fell rapidly toward the control level. Macrocytic erythrocytes, formed during exposure, remained macrocytic after the termination of exposure and after the loss of their reticulum. The posthypoxic mice proved sensitive for erythropoietin bioassay. Mice injected with normal dog serum showed a significantly higher incorporation of Fe-59 than control mice injected with physiologic saline. A reduction of the duration of exposure to 10 d resulted in only a slight decrease in the sensitivity of the mouse bioassay system. However, a 16-d exposure at a pressure of 360 mm Hg resulted in considerably less sensitive bioassay animals.
Huff, J. E.↗
Determinants of erythropoietin release in response to short-term hypobaric hypoxia
We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.
Non-NASA Center↗
CHOICE - Directed Study: Consequences of longterm- Confinement and Hypobaric HypOxia on Immunity in the Antarctic Concordia Environment
Concerning ground-based space physiological research, the choice of analog must carefully match the system of interest. For spaceflight-associated immune dysregulation (SAID), Antarctica winter-over has emerged as potentially the best terrestrial analog. The prolonged mission durations, extreme/dangerous environment, station-based lifestyle, isolation from outside world, disrupted circadian rhythms, and other psychological aspects make this analog extremely high fidelity for exploration-class space missions (long duration lunar, Mars). NASA, ESA and RSA are currently investigating SAID, with NASA currently operating the Integrated Immune flight study. It is desirable to have a ground analog for SAID validated, so that potential countermeasures might be validated terrestrially prior to during flight. For this presentation, NASA data collected on the winterover 2009 crewmembers, baseline through early deployment will be presented. Through early deployment (approximately 2-3 weeks at Concordia), phenotypic alterations included increased levels of memory T cells, shifts among the CD8+ T cell compartment to a more mature phenotype, and increases in constitutively activated T cells. CD8+/IFNg+ T cell percentages, and T cell blastogenesis functional responses were depressed early deployment as compared to healthy controls. In four compatible subjects, secreted T cell Th1/Th2 cytokines were measured following culture stimulation, and a Th2 shift was observed as compared to controls. Post-winter over frozen sample return will be required to determine if this shift persisted during the winter over period. Additionally, circadian rhythms remained altered compared to baseline, as determined through 5x daily cortisol measurements. Latent viral reactivation will not be determined until frozen sample return occurs.
Sams, Clarence↗
Improved Hypoxia Modeling for Nutrient Control Decisions in the Gulf of Mexico
The Gulf of Mexico Modeling Framework is a suite of coupled models linking the deposition and transport of sediment and nutrients to subsequent bio-geo chemical processes and the resulting effect on concentrations of dissolved oxygen in the coastal waters of Louisiana and Texas. Here, we examine the potential benefits of using multiple NASA remote sensing data products within this Modeling Framework for increasing the accuracy of the models and their utility for nutrient control decisions in the Gulf of Mexico. Our approach is divided into three components: evaluation and improvement of (a) the precipitation input data (b) atmospheric constituent concentrations in EPA's air quality/deposition model and (c) the calculation of algal biomass, organic carbon and suspended solids within the water quality/eutrophication models of the framework.
Habib, Shahid↗
Operational Data on Crew Exposures to Mild Hypobaric Hypoxia in Microgravity
No abstract available
Norcross, Jason↗
Can we increase the time of useful consciousness in personnel exposed to Hypoxia?
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Robert W Sanders↗
Effects of Mild Hypobaric Hypoxia on Behavioral Health and Performance Outcomes in NASA Exploration Atmosphere
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Steven R. Anderson↗
Sex comparisons in physiological and cognitive performance during hypoxic challenge
Within the tactical aviation community, human performance research lags in considering potential psychophysiological differences between male and female aviators due to little inclusion of females during the design and development of aircraft systems. A poor understanding of how male and female aviators differ with respect to human performance results in unknown potential sex differences on aeromedically relevant environmental stressors, perchance leading to suboptimal performance, safety, and health guidelines. For example, previous hypoxia studies have excluded female participants or lacked a sizeable sample to examine sex comparisons. As such, progress toward sensor development and improving hypoxia familiarization training are stunted due to limited knowledge of how individual differences, including sex, may or may not underlie hypoxia symptoms and performance impairment. Investigating sex differences bridges the gap between aerospace medicine and operational health, and addressing hypoxia is one of many facets yet to be studied. In the current study, we retrospectively examined N = 6 hypoxia studies with male-female participant samples (total, N = 189; male, n = 118; female, n = 71). We explored sex as a predictor of physiological response, sensory deficits, the severity of cognitive performance declines, and symptom manifestation via linear and binary logistic regression models. We found that the female sex predicted lower peripheral oxygen saturation and the likelihood of headache reporting in response to hypoxic challenge, yet explained little variance when combined with age and body mass index. The sensory and cognitive performance models did not converge, suggesting high intra-individual variability. Together, sex, age, and body mass index were not the most robust predictors in responses to hypoxic challenge; we cannot infer this for sensory deficits and cognitive performance within an experimentally induced hypoxic environment. The findings have implications for improving hypoxia familiarization training, monitoring sensor development, and emergency response and recovery protocols in case of a hypoxia occurrence suitable for all aircrew. We recommend continuing to elucidate the impact of sex and intrapersonal differences in hypoxia and other aeromedically relevant stressors in tactical aviation.
60 APPLIED LIFE SCIENCES↗
Transgene expression patterns indicate that spaceflight affects stress signal perception and transduction in arabidopsis
The use of plants as integral components of life support systems remains a cornerstone of strategies for long-term human habitation of space and extraterrestrial colonization. Spaceflight experiments over the past few decades have refined the hardware required to grow plants in low-earth orbit and have illuminated fundamental issues regarding spaceflight effects on plant growth and development. Potential incipient hypoxia, resulting from the lack of convection-driven gas movement, has emerged as a possible major impact of microgravity. We developed transgenic Arabidopsis containing the alcohol dehydrogenase (Adh) gene promoter linked to the beta-glucuronidase (GUS) reporter gene to address specifically the possibility that spaceflight induces the plant hypoxia response and to assess whether any spaceflight response was similar to control terrestrial hypoxia-induced gene expression patterns. The staining patterns resulting from a 5-d mission on the orbiter Columbia during mission STS-93 indicate that the Adh/GUS reporter gene was activated in roots during the flight. However, the patterns of expression were not identical to terrestrial control inductions. Moreover, although terrestrial hypoxia induces Adh/GUS expression in the shoot apex, no apex staining was observed in the spaceflight plants. This indicates that either the normal hypoxia response signaling is impaired in spaceflight or that spaceflight inappropriately induces Adh/GUS activity for reasons other than hypoxia.
manned↗
Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia
Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test response in the early phase of Antarctic wintering over con rms distinct immune suppressive effects seen after (sub-)acute hypobaric hypoxia. The reversal and overshooting reaction of cellular immune responses upon stimulation, but not the resting state, indicate either a) priming of immune answers and/or b) an uncoupled or disregulated control of cellular immune answers by auto-, para- and endocrine pathways. Further analyses and correlations are warranted. Acknowledgement: Supported by the European Space Agency (ESA), the French (IPEV) and Italian (PNRA) polar institutes, the German National Space Program (DLR, 50WB0719/WB0919), by BELSPO/PROEDEX/ESA (C90-380/-391), NASA and by the Concordia crews who have participated with great enthusiasm.
Crucian, Brian↗
Body fluid alterations during head-down bed rest in men at moderate altitude
To determine the effects of hypoxia on fluid balance responses to simulated zero-gravity, measurements were made in six subjects before and during -5 deg continuous head-down bed rest (HDBR) over 8 d at 10,678 ft. The same subjects were studied again at this altitude without HDBR as a control (CON) using a cross-over design. During this time, they maintained normal upright day-time activities, sleeping in the horizontal position at night. Fluid balance changes during HDBR in hypoxia were more pronounced than similar measurements previously reported from HDBR studies at sea level. Plasma volume loss was slightly greater and the diuresis and natriuresis were doubled in magnitude as compared to previous studies in normoxia and sustained for 4 d during hypoxia. These changes were associated with an immediate but transient rise in plasma atrial natriuretic peptide (ANP) to day 4 of 140 percent in HDBR and 41 percent in CON (p less than 0.005), followed by a decline towards baseline. Differences were less striking between HDBR and CON for plasma antidiuretic hormone and aldosterone, which were transiently reduced by HDBR. Plasma catecholamines showed a similar pattern to ANP in both HDBR and CON, suggesting that elevated ANP and catecholamines together accounted for the enhanced fluid shifts with HDBR during hypoxia.
Loeppky, J. A.↗
Products and methods for organ protection with noble nanoparticles
Products and methods for redirecting the pathological biochemical process of accumulation of reduced pyridine nucleotides under deleterious hypoxia conditions toward the reduction of the precursor salt and the biosynthesis of biologically compatible, antioxidant noble metal nanoparticles and the simultaneous restoring of the tissue redox state are provided. The products and methods have application in the treatment of hypoxia and hypoxia-related diseases and disorders. Such products and methods are also useful in organ transplantation and recovery, in screening of anti-hypoxia agents, and in detecting elevated levels of the reducing equivalents of the redox state, for example, NADH, NADPH, GSH, and TrxSH 2 , in cells, tissues, or organs.
Rozhkova, Elena A.↗
Estuarine nutrient pollution impact reduction assessment through euphotic zone avoidance/bypass considerations
The feasibility of reducing nutrient pollution impact by redirecting the effluent to depths below the euphotic zone was investigated for the deep estuarine Puget Sound region of the Salish Sea in the Pacific Northwest of America. The hypothesis tested was that the thickness of the outflow layer in deep estuaries may be greater than the euphotic zone depth, allowing a fraction of nutrients to be exported out passively through the layers immediately below. The euphotic zone depth in Puget Sound varies from 8 to 25 m while the depth of the outflow layer can reach up to ≈ 60 m. Outfall relocation strategies were tested on 99% of the anthropogenic nutrient loads currently delivered to Puget Sound. The impact was quantified using the previously established biophysical Salish Sea Model, using gross primary production and exposure to low dissolved oxygen (DO) levels as the metric (< 2 mg/L for hypoxia and < 5 mg/L for impairment). Eliminating nutrient pollution (above natural) from rivers and wastewater reduced hypoxia exposure by 8.1% and 11.2%, respectively. Relocating the outfalls to deeper waters resulted in improvements, but only in the sill-less sub-basins such as Whidbey, where hypoxia and DO impairment exposure decreased (7.9% and 6.8%, respectively). The presence of multiple sills and circulation cells in Puget Sound resulted in increased exposure and rendered nutrient bypass goals unfeasible as originally envisioned. However, an alternate nutrient export pathway was identified through bottom exchange flow out of Puget Sound via Whidbey Basin and Deception Pass. An unexpected reduction in the exchange outflow magnitude (≈ 4%) due additional (22%) freshwater discharged to the estuary bottom was also noted. The potential loss in circulation strength due to rerouting of natural surface freshwater through submerged deep-water outfalls is identified as a new unforeseen anthropogenic impact.
54 ENVIRONMENTAL SCIENCES↗
Two Alternative Splicing Variants of AtERF73/HRE1, HRE1α and HRE1β, Have Differential Transactivation Activities in Arabidopsis
AtERF73/HRE1 is an AP2/ERF transcription factor in Arabidopsis and has two distinct alternative splicing variants, HRE1α and HRE1β. In this study, we examined the differences between the molecular functions of HRE1α and HRE1β. We found that HRE1α and HRE1β are both involved in hypoxia response and root development and have transactivation activity. Two conserved motifs in the C-terminal region of HRE1α and HRE1β, EELL and LWSY-like, contributed to their transactivation activity, specifically the four E residues in the EELL motif and the MGLWS amino acid sequence at the end of the LWSY-like motif. The N-terminal region of HRE1β also showed transactivation activity, mediated by the VDDG motif, whereas that of HRE1α did not. The transactivation activity of HRE1β was stronger than that of HRE1α in Arabidopsis protoplasts. Both transcription factors transactivated downstream genes via the GCC box. RNA-sequencing analysis further supported that both HRE1α and HRE1β might regulate gene expression associated with the hypoxia stress response, although they may transactivate different subsets of genes in downstream pathways. Our results, together with previous studies, suggested that HRE1α and HRE1β differentially transactivate downstream genes in hypoxia response and root development in Arabidopsis.
36 MATERIALS SCIENCE↗
Oxygen Deficiency in Spaceflight & its Impact on Plants’ Adaptive Changes
The goal of this study was to investigate the effects of hypoxic conditions in spaceflight. The distribution of genes involved with hypoxia in Arabidopsis thaliana and Brassica rapa were analyzed with the results from past spaceflight experiments to evaluate genes for future studies. Transcriptomes data of two different spaceflight studies of Arabidopsis thaliana from the NASA GeneLab database, GLDS-7 and GLDS-17, were compared. DNA microarrays were utilized for transcription profiling to conduct these studies. For GLDS-7, the response in spaceflight was studied with approaches that collected gene expression data. Leaves, hypocotyls, and root tissues were compared to the whole plant. For GLDS-17, seedlings and undifferentiated cultured cells were placed in the Biological Research in Canisters (BRIC), specifically BRIC-16. The genes related to hypoxia in Arabidopsis thaliana from these two studies were compared to genes in Brassica rapa with the TOAST database to evaluate similarities. When transcriptomes were analyzed for GLDS-7 and 17, genes that were considered significant had p-values ≤ 0.05 and log fold change values ≤ -1 or ≥1. Sixteen genes fulfilled the criteria. The genes related to hypoxia were alcohol dehydrogenase, elongation factor, ethylene-responsive factor, GUS, heat-shock proteins, NAP, RAP2.12, and RD20. The genes most impacted by spaceflight were heat-shock proteins. These genes were compared with Brassica rapa through Arabidopsis Ensemble Orthology from the TOAST Database. Similarities were seen in alcohol dehydrogenase, elongation factor, ethylene-responsive factor, heat-shock proteins, NAP, and RAP2.12. Overall, transcription profiling indicates that plants’ survival in spaceflight is dependent on adaptive changes with gene expression. This study also indicates that there are similarities in gene expression between Arabidopsis thaliana and Brassica rapa with comparable gene expression. Future studies could include analyzing additional species to understand which genes could be modified to ensure better yield of space crops amid hypoxic conditions.
hypoxia↗
Determining the impacts of venoarterial extracorporeal membrane oxygenation on cerebral oxygenation using a one-dimensional blood flow simulator
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical system that provides rapid and short-term support for patients with cardiac failure. In many patients, pulmonary function is also impaired, resulting in poorly-oxygenated cardiac outflow competing against well-oxygenated VA-ECMO outflow, a condition known as North-South syndrome. North-South syndrome is a primary concern because of its potential to cause cerebral hypoxia, which has a critical influence on neurological complications often seen in this patient population. In order to reduce ischemic neurological complications, it is important to understand how clinical decisions regarding VA-ECMO parameters influence blood oxygenation. In our work, we studied the impacts of flow rate and cannulation site on oxygenation using a one-dimensional (1D) model to simulate blood flow. Our model was initially tested by comparing blood flow results to those observed from experimental work in VA-ECMO patients. The 1D model was combined with a two-phase flow model to simulate oxygenation. Additionally, the influence of various other clinician-tunable parameters on oxygenation in the common carotid arteries (CCAs) were tested, including, blood viscosity, cannula position within the insertion artery, heart rate, and systemic vascular resistance (SVR), as well as geometrical changes such as arterial radius and length. Our results indicated that blood oxygenation to the brain strongly depended on the cannula insertion site and the VA-ECMO flow rate with a weaker but potentially significant dependence on arterial radius. During femoral cannulation, VA-ECMO flow rates greater than ~4.9 L/min were needed to perfuse the CCAs. However, axillary and central cannulation began to perfuse the CCAs at significantly lower flow (~1 L/min). These results may help explain the incidence of cerebral hypoxia in this patient population and the common need to change cannulation strategies during treatment to address this clinical problem. While this work describes patient-averaged results, determining these relationships between VA-ECMO parameters and cerebral hypoxia is an important step towards future work to develop patient-specific models that clinicians can use to improve outcomes.
1D blood flow↗
Proteomic characterization of Mycobacterium tuberculosis subjected to carbon starvation
ABSTRACT Mycobacterium tuberculosis(Mtb) is the causative agent of tuberculosis (TB), the leading cause of infectious disease-related deaths worldwide. TB infections present on a spectrum from active to latent disease. In the human host,Mtbfaces hostile environments, such as nutrient deprivation, hypoxia, and low pH. Under these conditions,Mtbcan enter a dormant, but viable, state characterized by a lack of cell replication and increased resistance to antibiotics. DormantMtbposes a major challenge to curing infections and eradicating TB globally. We subjectedMtbmc 2 6020 (ΔlysAand ΔpanCD), a double auxotrophic strain, to carbon starvation (CS), a culture condition that induces growth stasis and mimics environmental conditions associated with dormancyin vivo. We provide a detailed analysis of the proteome in CS compared to replicating samples. We observed extensive proteomic reprogramming, with 36% of identified proteins significantly altered in CS. Many enzymes involved in oxidative phosphorylation and lipid metabolism were retained or more abundant in CS. The cell wall biosynthetic machinery was present in CS, although numerous changes in the abundance of peptidoglycan, arabinogalactan, and mycolic acid biosynthetic enzymes likely result in pronounced remodeling of the cell wall. Many clinically approved anti-TB drugs target cell wall biosynthesis, and we found that these enzymes were largely retained in CS. Lastly, we compared our results to those of other dormancy models and propose that CS produces a physiologically distinct state of stasis compared to hypoxia inMtb. IMPORTANCE Tuberculosis is a devastating human disease that kills over 1.2 million people a year. This disease is caused by the bacterial pathogenMycobacterium tuberculosis(Mtb).Mtbexcels at surviving in the human host by entering a non-replicating, dormant state. The current work investigated the proteomic changes thatMtbundergoes in response to carbon starvation, a culture condition that models dormancy. The authors found broad effects of carbon starvation on the proteome, with the relative abundance of 37% of proteins significantly altered. Protein changes related to cell wall biosynthesis, metabolism, and drug susceptibility are discussed. Proteins associated with a carbon starvation phenotype are identified, and results are compared to other dormancy models, including hypoxia.
Microbiology↗