Changes in the heart during hypoxia /an experimental morphological study/
Effect of acclimatization to hypoxia on mice resistance to acute hypoxia and radial acceleration and on heart morphology
HEART↗
SEARCH · Engineering Papers
Results for “hypoxia”
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Using Coupled Models to Study the Effects of River Discharge on Biogeochemical Cycling and Hypoxia in the Northern Gulf of Mexico
We describe emerging capabilities to understand physical processes and biogeoehemical cycles in coastal waters through the use of satellites, numerical models, and ship observations. Emerging capabilities provide significantly improved ability to model ecological systems and the impact of environmental management actions on them. The complex interaction of physical and biogeoehemical processes responsible for hypoxic events requires an integrated approach to research, monitoring, and modeling in order to fully define the processes leading to hypoxia. Our efforts characterizes the carbon cycle associated with river plumes and the export of organic matter and nutrients form coastal Louisiana wetlands and embayments in a spatially and temporally intensive manner previously not possible. Riverine nutrients clearly affect ecosystems in the northern Gulf of Mexico as evidenced in the occurrence of regional hypoxia events. Less known and largely unqualified is the export of organic matter and nutrients from the large areas of disappearing coastal wetlands and large embayments adjacent to the Louisiana Continental Shelf. This project provides new methods to track the river plume along the shelf and to estimate the rate of export of suspended inorganic and organic paniculate matter and dissolved organic matter form coastal habitats of south Louisiana.
COUPLED MODEL↗
Degradation-Resistant Hypoxia Inducible Factor-2α in Murine Osteocytes Promotes a High Bone Mass Phenotype
Molecular oxygen levels vary during development and disease. Adaptations to decreased oxygen bioavailability (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are composed of an oxygen-dependent α subunit (HIF-α), of which there are two transcriptionally active isoforms (HIF-1α and HIF-2α), and a constitutively expressed β subunit (HIFβ). Under normoxic conditions, HIF-α is hydroxylated via prolyl hydroxylase domain (PHD) proteins and targeted for degradation via Von Hippel-Lindau (VHL). Under hypoxic conditions, hydroxylation via PHD is inhibited, allowing for HIF-α stabilization and induction of target transcriptional changes. Our previous studies showed that Vhl deletion in osteocytes (Dmp1-cre; Vhlf/f) resulted in HIF-α stabilization and generation of a high bone mass (HBM) phenotype. The skeletal impact of HIF-1α accumulation has been well characterized; however, the unique skeletal impacts of HIF-2α remain understudied. Because osteocytes orchestrate skeletal development and homeostasis, we investigated the role of osteocytic HIF-α isoforms in driving HBM phenotypes via osteocyte-specific loss-of-function and gain-of-function HIF-1α and HIF-2α mutations in C57BL/6 female mice. Deletion of Hif1a or Hif2a in osteocytes showed no effect on skeletal microarchitecture. Constitutively stable, degradation-resistant HIF-2α (HIF-2α cDR), but not HIF-1α cDR, generated dramatic increases in bone mass, enhanced osteoclast activity, and expansion of metaphyseal marrow stromal tissue at the expense of hematopoietic tissue. Our studies reveal a novel influence of osteocytic HIF-2α in driving HBM phenotypes that can potentially be harnessed pharmacologically to improve bone mass and reduce fracture risk.
59 BASIC BIOLOGICAL SCIENCES↗
Hypoxia-cultured mouse mesenchymal stromal cells from bone marrow and compact bone display different phenotypic traits
Highlights: • Mouse compact bone is richer in MSC compared to central bone marrow. • Derivation of MSC from mouse compact bone is associated with lower risk of contamination with hematopoietic cells. • MSC from compact bone display higher osteogenic differentiation capacity than bone marrow MSC. It has been suggested that the bone marrow microenvironment harbors two distinct populations of mesenchymal stromal cells (MSC), one with a perivascular location and other present in the endosteum. A better understanding of the biology of these MSC subsets has been pursued in order to refine its clinical application. However, most comparative characterizations of mouse MSC have been performed in normoxia. This can result in misleading interpretations since mouse MSC subsets with low/defective p53 activity are known to be selected during culture in normoxia. Here, we report a comprehensive in vitro characterization of mouse MSC isolated from bone marrow (BM-MSC) and compact bone (CB-MSC) expanded and assayed under hypoxia for their morphology, clonogenic efficiency and differentiation capacity. We found that, under hypoxia, compact bone is richer in absolute numbers of MSC and isolation of MSC from compact bone is associated with a reduced risk of hematopoietic cell carryover. In addition, CB-MSC have higher in vitro osteogenic capacity than BM-MSC, while adipogenic differentiation potential is similar. These findings reinforce the hypothesis of the existence of MSC in bone marrow and compact bone representing functionally distinct cell populations and highlight the compact bone as an efficient source of murine MSC under physiological oxygen concentrations.
60 APPLIED LIFE SCIENCES↗
Transcutaneous and End-Tidal CO 2 Measurements in Hypoxia and Hyperoxia
BACKGROUND: Transcutaneous measurement of carbon dioxide (CO 2 ) has been proposed for physiological monitoring of tactical jet aircrew because in some clinical settings it mirrors arterial CO 2 partial pressure (P a co 2 ). End-tidal monitoring in laboratory settings is known to give high-fidelity estimates of P a co 2 . METHODS: The correspondence between end-tidal (P ET co 2 ) and transcutaneous Pco 2 (tcPco 2 ) was examined in healthy volunteers under laboratory conditions of hyperoxia and hypoxia. Rest and exercise, skin heating and cooling, hyperventilation, and induced CO 2 retention were employed. RESULTS: Neither measure followed all known changes in P a co 2 and tcPco 2 changed when the skin temperature near the probe changed. Bland-Altman analysis showed significant nonzero slopes under most conditions. Regression analysis indicated that oxygen partial pressure (Po 2 ) in tissue measured as transcutaneous Po 2 (tcPo 2 ) is an important explanatory variable for tcPco 2 in addition to P ET co 2 , and that local skin temperature also has an effect. Additionally, absorption atelectasis from breathing 100% O 2 may cause P ET co 2 to deviate from P a co 2 . DISCUSSION: Even as a trend indicator for P a co 2 , tcPco 2 is not useful under conditions that resemble those in the highly dynamic tactical jet aircraft environment. P ET co 2 is also not a good indicator of CO 2 status in pilots who breathe nearly 100% O 2 . Shykoff BE, Lee LR, Gallo M, Griswold CA. Transcutaneous and end-tidal CO 2 measurements in hypoxia and hyperoxia . Aerosp Med Hum Perform. 2021; 92(11):864–872 .
Biophysics↗
Hypothalamic self-stimulation - Interaction of hypoxia and stimulus intensity.
Hypoxia effects on skilled motor task by rats, investigating interaction of hypoxia and electric stimulus intensity on hypothalmic self stimulation
Annau, Z.↗
Circulatory responses to hypoxia in experimental myocardial infarction.
Three levels of decreased arterial oxygen saturation elicited a graded circulatory response in dogs, manifested by stepwise increases in cardiac output, left ventricular dp/dt, and stroke volume, and decreases in systemic vascular resistance. Responses to similar hypoxia challenges after experimental myocardial infarction were qualitatively similar but quantitatively less. Although the circulatory compensation for hypoxia was less effective after myocardial infarction, no further deterioration of the haemodynamics was noted.
Schroll, M.↗
Hypoxia, gas narcosis, and metabolic response to argon and nitrous oxide
Studies of the mechanism of inert gas influence on metabolism are reported. The studies reported include: metabolic response of hamsters to argon and nitrous oxide, membrane fatty acids and susceptability to narcotic gas influence, narcosis-induced histotoxic hypoxia, biochemical study of inert gas narcosis, hypoxia-induced protection against cardiovascular deterioration in the weightless state, and acute metabolic and physiologic response of goats to narcosis.
Source record↗
Observations on autoregulation in skeletal muscle - The effects of arterial hypoxia
An experimental study was carried out on 25 mongrel dogs of both sexes to re-evaluate autoregulation of blood flow in skeletal muscle, with particular reference to the steady-state resistance and transient response in muscle blood flow following a square wave increase in arterial perfusion pressure and to the examination of the effect of arterial hypoxia on this transient response. The data emphasize the importance of considering the transient changes in blood flow in evaluating the autoregulatory response in skeletal muscle. For quantification purposes, a parameter termed alpha is introduced which represents the ratio between the increase in blood flow from baseline to peak and the return of blood flow from the peak to the new steady-state. Such a quantification of the transient response in flow with step increases in perfusion pressure demonstrates substantial transient responses under conditions of normal oxygenation and progressive attenuation of flow transients with increasing hypoxia.
Pohost, G. M.↗
Effect of sinusoidal modulated currents and acute hypoxia on corticosterone content and activity of certain dehydrogenases in tissues of different rat organs during hypokinesia
The state of hypokinesia in rats was reproduced by keeping them for 30 days in special box cages that restricted their mobility in all directions. Results show the resistance to acute hypoxic hypoxia is increased. This is linked to the considerable rise in the reduced level of corticosterone in different organs and the succinate dehydrogenase activity in the liver and brain. The letter indicated the primary oxidation of succinate, which has great importance in the adaptation of the oxidative metabolism to acute oxygen insufficiency. The use of sinusoidal modulated currents in the period of hypokinesia promotes normalization of the indices for resistance of the rats to acute hypoxia.
Melik-Aslanova, L. L.↗
High Resolution ECG for Evaluation of Heart Function During Exposure to Subacute Hypobaric Hypoxia
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 due to exposure to high altitude.
Zupet, Petra↗
High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia
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.
Zupet, P.↗
Mild Normobaric Hypoxia Exposure for Human-Autonomy System Testing
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.
Stephens, Chad L.↗
Appetite and Food Intake During 11 Days of Mild Hypobaric Hypoxia
Introduction Reduced food consumption and loss of body mass and muscle mass have been observed during spaceflight. Hypoxic conditions that astronauts may encounter on exploration missions may further implicate satiety signals and dietary intake. Appetite, food intake, and satiety hormones were investigated under the conditions of mild hypoxia and high energy output during simulated extravehicular activity (EVA) to determine the adequacy of a mission relevant space food system to support energy balance and body composition. Methods Foods realistic to early Artemis missions was packed by meal for each subject for the 11-day test based on estimated energy requirements (EER) and estimated EVA caloric requirements. No hot water or food warmer was provided and only room temperature water was available to rehydrate food and beverages in-mission, mimicking plans for early Artemis missions. Measures included food records (pre-mission, in-mission); fasted body weight (pre-mission, in-mission); Dual-energy X-ray absorptiometry (DXA) (pre-mission, post-mission); subjective ratings and feedback of food acceptability, mealtime and meal preparation sufficiency, appetite, and nausea (in-mission); and circulating ghrelin and leptin concentration in fasted blood samples (pre-mission, in-mission: pre-post EVA). Results All subjects consumed fewer calories in-mission than predicted. On average, subjects consumed 341 calories less on EVA days compared to non-EVA days in-mission (p=0.0511). The total weight loss estimate from daily weight measurements (-1.1 kg, p=0.0028) is consistent with underconsumption and supported by DXA measurements (-1.3 kg total body mass, p=0.0123 and -1.6 kg fat mass, p=0.0016). In general, most foods that were consumed were given acceptable scores, but subject comments indicated that the most acceptable foods were those not intended to be heated. Comments also indicated that subjects found their favorite foods early in the mission and avoided the foods that they did not like throughout the mission. Habitability scores indicated that overall aspects of the food system were considered borderline or unacceptable over the length of this mission. Foods that caused gas were avoided pre-EVA to prevent discomfort during pressure changes. Average fruit and vegetable intake decreased during the mission, dropping from 4.8 servings/d pre-mission to 3.4 servings/d on non-EVA days in-mission (p=0.0872) and 2.3 servings on EVA days (p=0.0020). Fasting ghrelin concentrations tended to be lower pre-EVA and on non-EVA days when exposed to mild hypoxia compared to normoxic conditions pre-mission and post-EVA (p=0.0136). Fasting levels of leptin did not change. Discussion Food intake was reduced in-mission, resulting in a caloric deficit and weight loss for most subjects. Crew food and appetite ratings and comments indicated this was due to a combination of food choices, lack of preference, lack of preparation capability, lack of time for meal preparation, consumption, and cleanup, and physiological challenges with the changing pressure. The regulation of appetite stimulating hormone ghrelin, but not the appetite suppressor leptin, appeared to be sensitive to hypoxic conditions. Conclusions Food preparation capabilities and time for meals are important for promoting adequate food intake. Reduced appetite and food intake during missions may further be aggravated under hypoxic conditions through the suppression of ghrelin. Lack of time for meals on EVA days, and avoidance of potential gas-causing foods (e.g., health promoting fruits and vegetables) prior to EVAs, demonstrate the importance of scheduling ample recovery time between EVA days.
Grace L Douglas↗
Appetite and Food Intake During 11 Days of Mild Hypobaric Hypoxia
Introduction Reduced food consumption and loss of body mass and muscle mass have been observed during spaceflight. Hypoxic conditions that astronauts may encounter on exploration missions may further implicate satiety signals and dietary intake. Appetite, food intake, and satiety hormones were investigated under the conditions of mild hypoxia and high energy output during simulated extravehicular activity (EVA) to determine the adequacy of a mission relevant space food system to support energy balance and body composition. Methods Foods realistic to early Artemis missions was packed by meal for each subject for the 11-day test based on estimated energy requirements (EER) and estimated EVA caloric requirements. No hot water or food warmer was provided and only room temperature water was available to rehydrate food and beverages in-mission, mimicking plans for early Artemis missions. Measures included food records (pre-mission, in-mission); fasted body weight (pre-mission, in-mission); Dual-energy X-ray absorptiometry (DXA) (pre-mission, post-mission); subjective ratings and feedback of food acceptability, mealtime and meal preparation sufficiency, appetite, and nausea (in-mission); and circulating ghrelin and leptin concentration in fasted blood samples (pre-mission, in-mission: pre-post EVA). Results All subjects consumed fewer calories in-mission than predicted. On average, subjects consumed 341 calories less on EVA days compared to non-EVA days in-mission (p=0.0511). The total weight loss estimate from daily weight measurements (-1.1 kg, p=0.0028) is consistent with underconsumption and supported by DXA measurements (-1.3 kg total body mass, p=0.0123 and -1.6 kg fat mass, p=0.0016). In general, most foods that were consumed were given acceptable scores, but subject comments indicated that the most acceptable foods were those not intended to be heated. Comments also indicated that subjects found their favorite foods early in the mission and avoided the foods that they did not like throughout the mission. Habitability scores indicated that overall aspects of the food system were considered borderline or unacceptable over the length of this mission. Foods that caused gas were avoided pre-EVA to prevent discomfort during pressure changes. Average fruit and vegetable intake decreased during the mission, dropping from 4.8 servings/d pre-mission to 3.4 servings/d on non-EVA days in-mission (p=0.0872) and 2.3 servings on EVA days (p=0.0020). Fasting ghrelin concentrations tended to be lower pre-EVA and on non-EVA days when exposed to mild hypoxia compared to normoxic conditions pre-mission and post-EVA (p=0.0136). Fasting levels of leptin did not change. Discussion Food intake was reduced in-mission, resulting in a caloric deficit and weight loss for most subjects. Crew food and appetite ratings and comments indicated this was due to a combination of food choices, lack of preference, lack of preparation capability, lack of time for meal preparation, consumption, and cleanup, and physiological challenges with the changing pressure. The regulation of appetite stimulating hormone ghrelin, but not the appetite suppressor leptin, appeared to be sensitive to hypoxic conditions. Conclusions Food preparation capabilities and time for meals are important for promoting adequate food intake. Reduced appetite and food intake during missions may further be aggravated under hypoxic conditions through the suppression of ghrelin. Lack of time for meals on EVA days, and avoidance of potential gas-causing foods (e.g., health promoting fruits and vegetables) prior to EVAs, demonstrate the importance of scheduling ample recovery time between EVA days.
Lichar Dillon↗
Effects of Mild Hypobaric Hypoxia on Response From Mild Exercise in NASA Exploration Atmosphere Tests
INTRODUCTION: The NASA Exploration Atmosphere study aims to validate a new prebreathe protocol incorporating an alternate habitat atmosphere of 56.5 kPa (8.2psia), 34% O 2 , and 66% N 2 to control and mitigate decompression sickness risk associated with spaceflight extravehicular activities. This alternate atmosphere results in a mild hypoxic environment (PIO 2 of 128 mmHg) that may influence inhabitant physiological responses to exercise. Therefore, the responses to light exercise in relation to the mild hypobaric hypoxic environment were investigated. METHODS: Eight participants (4M/4F; age=38.3±9.0 yr; weight=76.0±13.1 kg; peak aerobic capacity [VO 2 pk]= 3.1±0.7 L/min) were exposed to a mild hypobaric hypoxic environment for 11 days in NASA’s 20-foot hypobaric chamber at Johnson Space Center. Participants alternated test days between a habitat atmosphere of 56.5 kPA/34% O 2 and simulated 6-hour EVA environment, 29.6 kPa/85% O 2 . Participants completed pre-mission graded VO 2 pk tests on a LODE cycle ergometer with ParvoMedics metabolic analyzer. Submaximal aerobic tests were performed pre and during the mission (10-minutes of exercise at a workload of 40% VO 2 pk).Pre-mission, performed submaximal exercise exposed to a breathing air mixture of, 18% O 2 and balance N 2 , to simulate the mildly hypoxic environment within the 20-foot chamber. Linear mixed models (fixed effect: test day; random effects: subject, age) were performed to determine whether physiological responses (oxygen uptake [VO 2 ], carbon dioxide production [VCO 2 ], ventilation [VE], oxygen saturation [SPO 2 ], heart rate [HR], respiratory exchange ratio [RER]) to submaximal exercise performed within the 20-foot hypobaric chamber every 2 days differed from the pre-mission (18% O 2 ) testing. Results are presented as estimated marginal means with lower and upper confidence limits, with significance set to 0.05. RESULTS AND DISCUSSION: Seven of eight participants completed the chamber study. Mixed models for VO 2 , VCO 2 , SpO 2 , HR, and RER indicated negligible impact of the mild hypoxic chamber environment compared to pre-mission testing (all p>0.05).Results for VE indicated a minor impact of chamber environment compared to pre-mission testing (37.0 L/min [30.8, 43.2]), with increased VE at test day 10 (40.4 L/min [34.2, 46.6]; p= 0.029).The aerobic performance data collected suggests limited physiologic responses to mild exercise when performed at normobaric hypoxia and hypobaric hypoxia.
B Siders↗
PathTracer Comprehensively Identifies Hypoxia-Induced Dormancy Adaptations in Mycobacterium tuberculosis
Mining large-scale data to discover biologically relevant information remains a challenge despite the rapid development of bioinformatics tools. Here, we have developed a new tool, PathTracer, to identify biologically relevant information flows by mining genome-wide protein–protein interaction networks following integration of gene expression data. PathTracer successfully mines interactions between genes and traces the most perturbed paths of perceived activities under the conditions of the study. Here, we further demonstrated the utility of this tool by identifying adaptation mechanisms of hypoxia-induced dormancy in Mycobacterium tuberculosis (Mtb).
59 BASIC BIOLOGICAL SCIENCES↗
Impacts of Sea‐Level Rise on Hypoxia and Phytoplankton Production in Chesapeake Bay: Model Prediction and Assessment
In this study, the influence of sea-level rise (SLR) on seasonal hypoxia and phytoplankton production in Chesapeake Bay is investigated using a 3D unstructured grid model. Three SLR scenarios (0.17, 0.5, and 1.0 m) were conducted from 1991 to 1995. Results show that the summer hypoxic volume (HV) increases about 2%, 8%, and 16%, respectively, for these three scenarios, compared with Base Scenario. The contributions of physical and biological processes on the increase in the HV were analyzed. With the projected SLR, enhanced gravitational circulation transports more oxygen-rich water in the bottom layer from the mouth. However, the pycnocline moves upwards along with increasing water depth, which largely prolongs the time for dissolved oxygen (DO) to be transported to the bottom. The altered physical processes contribute greatly to a larger HV bay-wide. Besides, SLR increases the whole Bay phytoplankton production, with a larger increase in shallow areas (e.g., 53% in areas with depth <1 m under SLR of 0.5 m). Enhanced light availability is suggested to be the major driver of blooming phytoplankton under SLR in shallow areas. While increased DO production over the euphotic zone is mostly released to the atmosphere and transported downstream, the increase in settled organic matter greatly promotes DO consumption in the water column. The increased respiration is another major cause of the HV increase besides the physical contributions.
54 ENVIRONMENTAL SCIENCES↗