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At least 145 records · Page 8

CO2-O2 interactions in extension of tolerance to acute hypoxia

Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

Lambertsen, C. J.↗

A review of available LC/50/ data

Several gaseous products of pyrolysis and combustion have been evaluated for LC/50/, defined as the concentration of toxic gas in the atmosphere being inhaled by test animals that will produce death in 50% of the animals within a given time period. The products tested included CO, HCl, HF, HCN, NO2, and SO2. It was found that HCN and NO2 were consistently the most toxic of the gases reviewed, and that mice were more susceptible than rats to HCl and HF, although less susceptible than rats to NO2. Extrapolation of LC/50/ data to humans indicates that metabolic rate may be a valid basis for extrapolation when the toxicity mechanism is interference with oxygen transport and utilization, or pulmonary edema, but not when it is irritation and damage to the upper respiratory tract.

Hilado, C. J.↗

Development of an in-line filter to prevent intrusion of NO2 toxic vapors into A/C systems

The hypergolic propellant nitrogen tetroxide (N2O4 or NTO) is routinely used in spacecraft launched at Kennedy Space Center (KSC) and Cape Canaveral Air Station (CCAS). In the case of a catastrophic failure of the spacecraft, there would be a release of the unspent propellant in the form of a toxic cloud. Inhalation of this material at downwind concentrations which may be as high as 20 parts per million (ppm) for 30 minutes in duration, may produce irritation to the eyes, nose and respiratory tract. Studies at both KSC and CCAS have shown that the indoor concentrations of N2O4 during a toxic release may range from 1 to 15 ppm and depend on the air change rate (ACR) for a particular building and whether or not the air conditioning (A/C) system has been shut down or left in an operating mode. This project was initiated in order to assess how current A/C systems could be easily modified to prevent personnel from being exposed to toxic vapors. A sample system has been constructed to test the ability of several types of filter material to capture the N2O4 vapors prior to their infiltration into the A/C system. Test results will be presented which compare the efficiencies of standard A/C filters, water wash systems, and chemically impregnated filter material in taking toxic vapors out of the incoming air stream.

Meneghelli, Barry↗

Prolonged triboluminescence in clays and other minerals

Samples of various clays and minerals were ground or fractured and monitored with a liquid scintillation spectrometer in order to obtain triboluminescent decay curves. Kaolinite samples displayed several million counts/min after grinding, with a surface area emission estimated at tens of billions of photons/sq cm of surface. The photon production rates varied with the origin of the sample, and kaolinite continually yielded higher production rates than bentonite. The addition of water to the samples slightly increased the count rate of emitted light, while the addition of the fluorescent molecule substance tryptofan significantly enhanced the count rate. Freezing smears of kaolinite and montmorillonite in liquid nitrogen and in a salt ice mixture also induced triboluminescence in the montmorillonite. A possible connection between powdery triboluminescent materials formed in mining industries and respiratory disorders among miners is suggested.

Lahav, N.↗

Swimming kinematics and respiratory behaviour of Xenopus laevis larvae raised in altered gravity

We examined the respiratory behaviours and swimming kinematics of Xenopus laevis tadpoles hatched in microgravity (Space Shuttle), simulated microgravity (clinostat) and hypergravity (3 g centrifuge). All observations were made in the normal 1 g environment. Previous research has shown that X. laevis raised in microgravity exhibit abnormalities in their lungs and vestibular system upon return to 1 g. The tadpoles raised in true microgravity exhibited a significantly lower tailbeat frequency than onboard 1 g centrifuge controls on the day of landing (day0), but this behaviour normalized within 9 days. The two groups did not differ significantly in buccal pumping rates. Altered buoyancy in the space-flight microgravity tadpoles was indicated by an increased swimming angle on the day after landing (day1). Tadpoles raised in simulated microgravity differed to a greater extent in swimming behaviours from their 1 g controls. The tadpoles raised in hypergravity showed no substantive effects on the development of swimming or respiratory behaviours, except swimming angle. Together, these results show that microgravity has a transient effect on the development of locomotion in X. laevis tadpoles, most notably on swimming angle, indicative of stunted lung development. On the basis of the behaviours we studied, there is no indication of neuromuscular retardation in amphibians associated with embryogenesis in microgravity.

Flight Experiment↗

Effect of Diet on Metabolism of Laboratory Rats

In previous studies when rats were fed a processed, semipurified, extruded rodent food bar (RFB) developed for space science research, we noted a difference in the appearance of gastrointestinal tissue (GI); therefore the following study evaluated GI characteristics and growth and metabolic rates of rats fed chow (C) or RFB. Two hundred and twenty-four rats (78 g mean body weight) were randomly assigned to 28 cages and provided C or RFB. Each cage was considered the experimental unit and a 95 percent level of significance, indicated by ANOVA, was used for inference. After each 30-, 60-, and 90-day period, eight cages were shifted from the C to RFB diet and housing density was reduced by two rats per cage. The two rats removed from each cage were sacrificed and used for GI evaluation. Metabolic rates of the rats in each cage were determined by indirect calorimetry. No differences in body weight were detected at 0, 30, 60 or 90 days between C and RFB. Heat production (kcal/hr/kg), CO2 production (L/hr/kg) and O2 consumption (L/hr/kg) were different by light:dark and age with no effect of diet. Respiratory quotient was different by age with no effect of light:dark or diet. Rats on the C diet ate less food and drank more water than those on RFB. C rats produced more fecal and waste materials than the RFB. GI lengths increased with age but were less in RFB than C. GI full and empty weights increased with age but weighed less in RFB than C. Gut-associated lymphoid tissue (GALT) numbers increased with age with no effect of diet. No differences in ileum-associated GALT area were detected between C and RFB. Switching C to RFB decreased GI length, GI full and empty weights, with no changes in GALT number or area. We concluded RFB decreased GI mass without affecting metabolic rate or general body growth.

Harrison, P. C.↗

Physiological basis for human autonomic rhythms

Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a measurement that identifies functional reflex abnormalities contributing to terminal dysrhythmias.

Review, Tutorial↗

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

NASA Discipline Cardiopulmonary↗

Constraint-Free Measurement of Metabolic Rate

By using hardware and software originally developed for manned spacecraft, metabolism is now measured while subject wears a loose-fitting mask. This more comfortable, less-restrictive measurement technique uses speed, accuracy and control capabilities of a microcomputer. Because mask imposes minimum interference to subject undergoing testing, it can be used to measure respiratory responses to such activities as treadmill exercise. Mask can be worn for long periods with little discomfort.

Koester, K. L.↗

Study of the effect of space cabin environment on susceptibility to disease

Decreased resistance to infections initiated by respiratory challenge with Klebsiella pneumoniae or influenza virus was observed in mice maintained in a simulated space cabin environment represented by 98% oxygen atmosphere and 27,000 ft altitude (5 psi). The reduced resistance was manifested by increased mortality rates as compared to those seen in mice maintained at ground level condition. However, an adaptation to the stress appeared to be present in mice exposed to the space cabin environment for extended time period, i.e. 36 days, and then challenged with the influenza virus. Reduced resistance was not observed when Salmonella typhimurium was used as the challenge agent. Histopathologic examination of lungs of mice indicated that the severity of damage appeared to be related to the duration of exposure to the simulated space cabin environment.

Source record↗

In Vivo Model to Test Implanted Biosensors for Blood pH

Biosensors for monitoring physiologic data continuously through telemetry are available for heart rate, respiration, and temperature but not for blood pH or ions affected by hydrogen ion concentration. A telemetric biosensor for monitoring blood pH on-line could be used to identify and manage problems in fluid and electrolyte metabolism, cardiac and respiratory function during space flight and the acid-base status of patients without the need for venipuncture in patients on Earth. Critical to the development of biosensors is a method for evaluating their performance after implantation. Mature rats, prepared with jugular, cannulas for repeated blood samples, were exposed to a gas mixture containing high levels of carbon dioxide (7%) in a closed environment to induce mild respiratory acidosis. Serial blood gas and pH measurements in venous blood were compared with electrical responses from sensors implanted in the subcutaneous tissue. Animals became slightly tachypneic after exposure to excess CO2, but remained alert and active. After 5 minutes, basal blood pH decreased from 7.404 +/- 0.013 to 7.289 +/- 0.010 (p less than 0.001)and PC02 increased from 45 +/- 6 to 65 +/- 4 mm. Hg (p les than 0.001). Thereafter pH and blood gas parameters remained stable. Implanted sensors showed a decrease in millivolts (mV) which paralleled the change in pH and averaged 5-6 mV per 0.1 unit pH. Implanted sensors remained sensitive to modest changes in tissue pH for one week. A system for inducing acidosis in rats was developed to test the in vivo performance of pH biosensors. The system provides a method which is sensitive, rapid and reproducible in the same and different animals with full recovery, for testing the performance of sensors implanted in subcutaneous tissues.

Arnaud, Sara B.↗

Adverse Neurological Effects of Wildfire Smoke

The respiratory and cardiovascular effects of smoke exposure are well documented from cigarette smoking and particulate matter (PM) associated with air-pollution studies, but epidemiological data also suggests exposure to high levels of woodsmoke correlate with central-nervous-system (CNS) dysfunction, including elevated rates of Alzheimer’s disease (AD) and dementia. Neuro-inflammation is believed to initiate the majority of Alzheimer’s and other neurodegenerative diseases attributed to environmental factors. We investigated whether inhaled PM and specific classes of compounds in wildfire smoke condensate extract (WSE) reach the brain and cause neuro-inflammation that can lead to progressive neurological degeneration, using isotope tracing of labeled particulate matter and major compound classes, biomarkers of blood-brain barrier (BBB) integrity, and biomarkers of neuro-inflammation. This project showed that inhalation exposure to PM and major compound classes present in WSE reached the brain through absorption in the nasal cavity and systemic circulation across the BBB. Twenty-four exposures of WSE to brain endothelial cells that form the main physical barrier of the BBB produced dose-dependent increases in biomarkers of inflammation and decreases in tight junction markers between cells. Intranasal exposure to WSE caused inflammatory disfunction in lung and brain. Biomarkers of inflammation increased and an enzyme inhibiting inflammation decreased. Similar patterns of chemical-induced changes in the lung and brain suggest either: (1) chemicals may act through shared molecular pathways upon entering lung and brain, or (2) that mediators originating in the lung circulate systemically to the brain and drive neuroinflammation. These findings warrant further mechanistic studies to delineate the temporal sequence of events to establish the lung-brain axis.

54 ENVIRONMENTAL SCIENCES↗

Controlled breathing protocols probe human autonomic cardiovascular rhythms

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

Non-NASA Center↗

Respiratory sinus arrhythmia: time domain characterization using autoregressive moving average analysis

Fourier-based techniques are mathematically noncausal and are therefore limited in their application to feedback-containing systems, such as the cardiovascular system. In this study, a mathematically causal time domain technique, autoregressive moving average (ARMA) analysis, was used to parameterize the relations of respiration and arterial blood pressure to heart rate in eight humans before and during total cardiac autonomic blockade. Impulse-response curves thus generated showed the relation of respiration to heart rate to be characterized by an immediate increase in heart rate of 9.1 +/- 1.8 beats.min-1.l-1, followed by a transient mild decrease in heart rate to -1.2 +/- 0.5 beats.min-1.l-1 below baseline. The relation of blood pressure to heart rate was characterized by a slower decrease in heart rate of -0.5 +/- 0.1 beats.min-1.mmHg-1, followed by a gradual return to baseline. Both of these relations nearly disappeared after autonomic blockade, indicating autonomic mediation. Maximum values obtained from the respiration to heart rate impulse responses were also well correlated with frequency domain measures of high-frequency "vagal" heart rate control (r = 0.88). ARMA analysis may be useful as a time domain representation of autonomic heart rate control for cardiovascular modeling.

NASA Discipline Regulatory Physiology↗

Electromagnetic Basis of Metabolism and Heredity

Living organisms control their cellular biological clocks to maintain functional oscillation of the redox cycle, also called the "metabolic cycle" or "respiratory cycle". Organization of cellular processes requires parallel processing on a synchronized time-base. These clocks coordinate the timing of all biochemical processes in the cell, including energy production, DNA replication, and RNA transcription. When this universal time keeping function is perturbed by exogenous induction of reactive oxygen species (ROS), the rate of metabolism changes. This causes oxidative stress, aging and mutations. Therefore, good temporal coordination of the redox cycle not only actively prevents chemical conflict between the reductive and oxidative partial reactions; it also maintains genome integrity and lifespan. Moreover, this universal biochemical rhythm can be disrupted by ROS induction in vivo. This in turn can be achieved by blocking the electron transport chain either endogenously or exogenously by various metabolites, e.g. hydrogen sulfide (H2S), highly diffusible drugs, and carbon monoxide (CO). Alternatively, the electron transport in vivo can be attenuated via a coherent or interfering transfer of energy from exogenous ultralow frequency (ULF) and extremely low frequency (ELF) electromagnetic (EM) fields, suggesting that-on Earth-such ambient fields are an omnipresent (and probably crucially important) factor for the time-setting basis of universal biochemical reactions in living cells. Our work demonstrated previously un-described evidence for quantum effects in biology by electromagnetic coupling below thermal noise at the universal electron transport chain (ETC) in vivo.

Electromagnetic↗

Operation of an experimental algal gas exchanger for use in a CELSS

Concepts of a Closed Ecological Life Support System (CELSS) anticipate the use of photosynthetic organisms (higher plants and algae) for air revitalization. The rates of production and uptake of carbon dioxide and oxygen between the crew and the photosynthetic organisms are mismatched. An algal system used for gas exchange only will have the difficulty of an accumulation or depletion of these gases beyond physiologically tolerable limits (in a closed system the mismatch between assimilatory quotient (AQ) and respiratory quotient (RQ) is balanced by the operation of the waste processor). The results are given of a study designed to test the feasibility of using environmental manipulations to maintain physiologically appropriate atmospheres for algae and mice in a gas closed system. Specifically, the atmosphere behavior of this system is considered with algae grown on nitrate or urea and at different light intensities and optical densities. Manipulation of both allow operation of the system in a gas stable manner. Operation of such a system in a CELSS may be useful for reduction of buffer sizes, as a backup system for higher plant air revitalization and to supply extra oxygen to the waste processor or during crew changes.

Smernoff, David T.↗

Improved deep learning prediction of antigen–antibody interactions

Identifying antibodies that neutralize specific antigens is crucial for developing effective immunotherapies, but this task remains challenging for many target antigens. The rise of deep learning–based computational approaches presents a promising avenue to address this challenge. Here, we assess the performance of a deep learning approach through two benchmark tests aimed at predicting antibodies for the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Three different strategies for constructing input sequence alignments are employed for predicting structural models of antigen–antibody complexes. In our initial testing set, which comprises known experimental structures, these strategies collectively yield a significant top-ranked prediction for 61% of cases and a success rate of 47%. Notably, one strategy that utilizes the sequences of known antigen binders outperforms the other two, achieving a precision of 90% in a subsequent test set of ~1,000 antibodies, balanced between true and control antibodies for the antigen, albeit with a lower recall of 25%. Our results underscore the potential of integrating deep learning methods with single B cell sequencing techniques to enhance the prediction accuracy of antigen–antibody interactions.

Science & Technology - Other Topics↗

Oxygen transport and cardiovascular function at extreme altitude: lessons from Operation Everest II

Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired PO2 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged 21-31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood gases were PO2 = 30 mmHg and PCO2 = 11 mmHg, pH = 7.56. Their maximal oxygen uptake decreased from 3.98 +/- 0.2 L/min at sea level to 1.17 +/- 0.08 L/min at PIO2 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation--a four fold increase. (2) Diffusion from the alveolus to end capillary blood--unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography and electrocardiography)--normal--although maximum cardiac output and heart rate were reduced. (4) Oxygen extraction--maximal with PvO2 14.8 +/- 1 mmHg. With increasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes.

Non-NASA Center↗