SEARCH · Search NASA
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Chemistry and physiology of carbon dioxide - carbamates of peptides and hemoglobin, molecular structure of carbonic anhydrase, enzymatic carboxylation, and respiratory gas exchange
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.
The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.
Physiological waveform simulator is capable of producing signals to simulate an axiliary and a sternal electrocardiogram, blood pressure, respiratory rate and body temperature. This may be used to check out bioinstrumentation.
The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation. In addition, the use of physiological profiles in the prediction of motion sickness was evaluated. Sixty subjects ingested either 0.6 mg scopolamine, 2.5 mg methoscopolamine, or a placebo. Heart rate (HR), respiratory sinus arrhythmia (an index of vagal tone), and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum. Compared to the other groups, the scopolamine group reported fewer motion sickness symptoms, and displayed lower HR, higher vagal tone, enhanced normal gastric myoelectric activity, and depressed gastric dysrhythmias before and during motion sickness induction. Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not. Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions, and by maintaining normal (3 cpm) electrogastrographic activity during drum rotation. It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability.
We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.
A 10-kg male pig-tailed monkey (Macaca nemestrina) was selected as an optimal species for spaceflight studies on weightlessness. Three days before the simulated launch, the animal was placed in a fiberglass pod system to provide continuous measurement of respiratory gas exchange. Attention is given to examining the effects of weightlessness on several basic parameters of metabolic and cardiovascular function in an adult nonhuman primate. The 10.7-day total simulated-experiment period consisted of preflight 2.6 days, inflight 6.3 days, and postflight 1.8 days. Statistically significant diurnal variation was noted in oxygen consumption and CO2 production rates, body temperature and HR, but not in respiratory quotient or blood pressure. The high quality of the continuous data obtained demonstrates the feasibility of performing sound physiological experimentation on nonhuman primates in the Spacelab environment.
Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.
Monkey physiological responses from lift-off to orbital insertion, showing EEG and EMG arousal reactions, motion sickness development, cardiovascular and respiratory changes
Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.
Development of improved positive pressure breathing garments for altitude and acceleration protection has occurred without collection of sufficient physiological data to understand the mechanisms of the improvement. Furthermore, modeling of the predicted response of future enhanced garments is greatly hampered by this lack of information. A joint, international effort is under way between Canada's Defense and Civil Institute for Environmental Medicine (DCIEM) and the US Navy's Naval Air Warfare Center Aircraft Division, Warminster (NAWCACDIVWAR). Using a Canadian subject pool, experiments at both the DCIEM altitude facility and the NAWCADIVWAR Dynamic Flight Simulator have been conducted to determine the cardiovascular and respiratory consequences of high levels of positive pressure breathing for altitude and positive pressure breathing for acceleration protection. Various improved pressure breathing garments were used to collect comparative physiological and performance data. New pressure breathing level and durahon capabilities have been encountered. Further studies will address further improvements in pressure suit design and correlation of altitude and acceleration data.
Biomedical data were collected during high-G portions of 11 YF-16 test flights. Test pilots monitored revealed increased respiratory rate and volume, decreased tidal volume, and increased heart rate at higher G levels, with one pilot exhibiting various cardiac arrhythmias. Anti-G suit inflation and pressurization lags varied inversely with G-onset rate, and suit pressurization slope was near the design value.
Analysis of human breath is a nonintrusive method to monitor both endogenous and exogenous chemicals found in the body. Several technologies were investigated and developed which are applicable to monitoring some organic molecules important in both physiological and pathological states. Two methods were developed for enriching the organic molecules exhaled in the breath of humans. One device is based on a respiratory face mask fitted with a polyethylene foam wafer; while the other device is a cryogenic trap utilizing an organic solvent. Using laboratory workers as controls, two organic molecules which occurred in the enriched breath of all subjects were tentatively identified as lactic acid and contisol. Both of these substances occurred in breath in sufficient amounts that the conventional method of gas-liquid chromatography was adequate for detection and quantification. To detect and quantitate trace amounts of chemicals in breath, another type of technology was developed in which analysis was conducted using high pressure liquid chromatography and mass spectrometry.
BACKGROUND: We tested the hypothesis that a common oscillatory pattern might characterize the rhythmic discharge of muscle sympathetic nerve activity (MSNA) and the spontaneous variability of heart rate and systolic arterial pressure (SAP) during a physiological increase of sympathetic activity induced by the head-up tilt maneuver. METHODS AND RESULTS: Ten healthy subjects underwent continuous recordings of ECG, intra-arterial pressure, respiratory activity, central venous pressure, and MSNA, both in the recumbent position and during 75 degrees head-up tilt. Venous samplings for catecholamine assessment were obtained at rest and during the fifth minute of tilt. Spectrum and cross-spectrum analyses of R-R interval, SAP, and MSNA variabilities and of respiratory activity provided the low (LF, 0.1 Hz) and high frequency (HF, 0.27 Hz) rhythmic components of each signal and assessed their linear relationships. Compared with the recumbent position, tilt reduced central venous pressure, but blood pressure was unchanged. Heart rate, MSNA, and plasma epinephrine and norepinephrine levels increased, suggesting a marked enhancement of overall sympathetic activity. During tilt, LF(MSNA) increased compared with the level in the supine position; this mirrored similar changes observed in the LF components of R-R interval and SAP variabilities. The increase of LF(MSNA) was proportional to the amount of the sympathetic discharge. The coupling between LF components of MSNA and R-R interval and SAP variabilities was enhanced during tilt compared with rest. CONCLUSIONS: During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.
Pulse and respiratory fluctuations of intercranial pressure in hermetic cavity
A fiberglass system was previously described, using which quantitative physiological measurements could be made to study the effects of weightlessness on 10 to 14 kg adult monkeys maintained in comfortable restraint under space flight conditions. Recent improvements in the system have made it possible to obtain continuous measurements of respiratory gas exchange, cardiovascular function, and mineral balance for periods of up to 30 days on pig-tailed monkeys. It has also been possible to operate two pods which share one set of instrumentation, thereby permitting simultaneous measurements to be made on two animals by commutating signal outputs from the pods. In principle, more than two pods could be operated in this fashion. The system is compatible with Spacelab design. Representative physiological data from ground tests of the system are presented.
BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.
Submaximal exercise stress tests were conducted preflight and postflight on the Apollo 14-17 crewmen. A bicycle ergometer was utilized to evoke target heart rates up to 160 beats/min while respiratory gas exchange, blood pressure, and cardiac output were measured. Three preflight tests were conducted during the month prior to flight to establish baseline values for postflight comparisons. Tachycardia was evidenced at rest and during exercise immediately postflight. This transitory tachycardia compensated for reduced stroke volume. Systolic blood pressure was reduced during exercise stress, but no consistent changes were observed in diastolic blood pressure. With the exception of the Apollo 15 crewmen, all crewmen had returned to preflight response levels by the day following recovery. No changes were observed in mechanical or respiratory efficiency immediately postflight.