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At least 433 records · Page 24

Mathematical modeling of fluid-electrolyte alterations during weightlessness

Fluid electrolyte metabolism and renal endocrine control as it pertains to adaptation to weightlessness were studied. The mathematical models that have been particularly useful are discussed. However, the focus of the report is on the physiological meaning of the computer studies. A discussion of the major ground based analogs of weightlessness are included; for example, head down tilt, water immersion, and bed rest, and a comparison of findings. Several important zero g phenomena are described, including acute fluid volume regulation, blood volume regulation, circulatory changes, longer term fluid electrolyte adaptations, hormonal regulation, and body composition changes. Hypotheses are offered to explain the major findings in each area and these are integrated into a larger hypothesis of space flight adaptation. A conceptual foundation for fluid electrolyte metabolism, blood volume regulation, and cardiovascular regulation is reported.

Leonard, J. I.↗

Autonomic Responses to Microgravity

The purpose of this report is to describe how changes in autonomic nervous system responses may be used as an index of individual differences in adaptational capacity to space flight. During two separate Spacelab missions, six crewmembers wore an ambulatory monitoring system which enabled continuous recording of their physiological responses for up to twelve hours a day for 3 to 5 mission days. The responses recorded were electrocardiography, respiration wave form, skin conductance level, hand temperature, blood flow to the hands and triaxial accelerations of the head and upper body. Three of these subjects had been given training, before the mission, in voluntary control of these autonomic responses as a means of facilitating adaptation to space. Three of these subjects served as Controls, i.e., did not receive this training but took anti-motion sickness medication. Nearly 300 hours of flight data are summarized. These data were examined using time-series analyses, spectral analyses of heart rate variability, and analyses of variance. Information was obtained on responses to space motion sickness, inflight medications, circadian rhythm, workload and fatigue. Preliminary assessment was made on the effectiveness of self-regulation training as a means of facilitating adaptation, with recommendations for future flights.

Toscano, W. B.↗

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗

Recent bed rest results and countermeasure development at NASA

Bedrest studies of normal subjects provide opportunities to understand physiologic responses to supine posture and inactivity. Furthermore, head-down tilt has been a valuable procedure to investigate adaptation to microgravity and development of countermeasures to maintain the health and well-being of humans during space-flight. Recent bedrest experiments at NASA have ranged in duration from a few hours to 17 weeks. Acute studies of 6 degrees head-down tilt indicate that elevation of capillary blood pressure from 28 to 34 mm Hg and increased capillary perfusion in tissues of the head cause facial and intracranial edema. Intracranial pressure increases from 2 to 17 mm Hg going from upright posture to 6 degrees head-down tilt. Microvessels of the head have a low capacity to constrict and diminish local perfusion. Elevation of blood and tissue fluid pressures/flow in the head may also explain the higher headward bone density associated with long-term head-down tilt. These mechanistic studies of head-down tilt, along with a better understanding of the relative stresses involved with upright posture and lower body negative pressure, have facilitated development of suitable physiologic countermeasures to maintain astronaut health during microgravity. Presently no exercise hardware is available to provide a blood pressure gradient from head to feet in space. However, recent studies in our laboratory suggest that treadmill exercise using a graded lower-body compression suit and 100 mmHg lower body negative pressure provides equivalent or greater physiologic stress than similar upright exercise on Earth. Therefore, exercise within a lower body negative pressure chamber may provide a cost-effective and simple countermeasure to maintain the cardiovascular and neuro-musculoskeletal systems of astronauts during long-duration flight.

manned↗

Physiologic mechanisms of circulatory and body fluid losses in weightlessness identified by mathematical modeling

Central volume expansion due to fluid shifts in weightlessness is believed to activate adaptive reflexes which ultimately result in a reduction of the total circulating blood volume. However, the flight data suggests that a central volume overdistention does not persist, in which case some other factor or factors must be responsible for body fluid losses. We used a computer simulation to test the hypothesis that factors other than central volume overdistention are involved in the loss of blood volume and other body fluid volumes observed in weightlessness and in weightless simulations. Additionally, the simulation was used to identify these factors. The results predict that atrial volumes and pressures return to their prebedrest baseline values within the first day of exposure to head down tilt (HDT) as the blood volume is reduced by an elevated urine formation. They indicate that the mechanisms for large and prolonged body fluid losses in weightlessness is red cell hemoconcentration that elevates blood viscosity and peripheral resistance, thereby lowering capillary pressure. This causes a prolonged alteration of the balance of Starling forces, depressing the extracellular fluid volume until the hematocrit is returned to normal through a reduction of the red cell mass, which also allows some restoration of the plasma volume. We conclude that the red cell mass becomes the physiologic driver for a large 'undershoot' of the body fluid volumes after the normalization of atrial volumes and pressures.

Simanonok, K. E.↗

Modification of Motion Perception and Manual Control Following Short-Durations Spaceflight

Adaptive changes during space flight in how the brain integrates vestibular cues with other sensory information can lead to impaired movement coordination and spatial disorientation following G-transitions. This ESA-NASA study was designed to examine both the physiological basis and operational implications for disorientation and tilt-translation disturbances following short-duration spaceflights. The goals of this study were to (1) examine the effects of stimulus frequency on adaptive changes in motion perception during passive tilt and translation motion, (2) quantify decrements in manual control of tilt motion, and (3) evaluate vibrotactile feedback as a sensorimotor countermeasure.

Wood, S. J.↗

Early cardiovascular adaptation to simulated zero gravity

A study was conducted on five normal male volunteers (23-29 yr), under controlled conditions, to evaluate early adaptive responses to zero gravity. Specific objectives are (1) to characterize the hemodynamic, renal and hormonal responses to a central fluid shift, and (2) to compare data obtained during and after head-down tilt with corresponding data from actual space flight to validate tilt as a physiological model for simulation of zero gravity. Zero gravity is simulated by a 24-hr period of head-down tilt at 5 deg. The results suggest that hemodynamic adaptation occurs rapidly and is essentially accomplished by 6 hr, and that adaptation includes diuresis and reduction in blood volume. The validity of head-down tilt at 5 deg as an experimental model is established by comparing the results obtained with data from Apollo and Skylab astronauts on body fluid distributions and postflight responses to orthostatic and exercise stress.

Nixon, J. V.↗

Endocrine and metabolic changes in payload specialist (L-1)

The endocrine system plays an important role in the adaptation to unusual environments by secreting hormones to control metabolism. Since human beings have long evolved on the surface of the Earth under a gravity environment, the weightless environment must be quite unusual for them. The purpose of this experiment is to study the mechanisms of human adaptation to a weightless environment from endocrine and metabolic changes. Our study plan is focused on four major physiological changes which were reported during past space flights or which may be expected to occur under that condition: (1) hormone and metabolic changes associated with fluid shift; (2) bone demineralization and muscle atrophy; (3) altered circadian rhythm; and (4) stress reaction during space flight.

Matsui, Nobuo↗

CO2-O2 Interactions in Extension of Tolerance to Acute Hypoxia

Advantageous and/or detrimental influences associated with purposeful deviations from atmospheric levels of O2 and CO2 are studied. Specific goals have been directed to simulating situations of emergency or accidental exposure to hypoxic (10% O2) environments. They included establishing dynamic effects of hypoxia with and without CO2 (rate of acute adaptation), and stable-state (equilibrium) effects on blood and brain oxygenation. They also included effects on the physiological parameters of respiration and blood gas composition which underlie brain oxygenation. For 10% O2, a complete experiment consisted of three identical rest-exercise phases of 32 minutes duration. Following a five minute air control period, each inspired gas was administered over the next 27 minutes. The test gases were room air control, 10% +/- 0.1% O2 with 4% +/- 0.1% CO2, and 10% +/- 0.1% O2. A minimum of 45 minutes separated each phase. Relative to inspiration of 10% O2, brain oxygenation is enhanced by addition of 4% CO2. This is accomplished by increasing the rate at which O2 in arterial blood is supplied to the brain circulation (well above even the normoxic level), and on relative improvement in the arterial pressure of O2.

Lambertsen, C. J.↗

Adaptation, plant evolution, and the fossil record

The importance of adaptation in determining patterns of evolution has become an important focus of debate in evolutionary biology. As it pertains to paleobotany, the issue is whether or not adaptive evolution mediated by natural selection is sufficient to explain the stratigraphic distributions of taxa and character states observed in the plant fossil record. One means of addressing this question is the functional evaluation of stratigraphic series of plant organs set in the context of paleoenvironmental change and temporal patterns of floral composition within environments. For certain organ systems, quantitative estimates of biophysical performance can be made on the basis of structures preserved in the fossil record. Performance estimates for plants separated in time or space can be compared directly. Implicit in different hypotheses of the forces that shape the evolutionary record (e.g. adaptation, mass extinction, rapid environmental change, chance) are predictions about stratigraphic and paleoenvironmental trends in the efficacy of functional performance. Existing data suggest that following the evolution of a significant structural innovation, adaptation for improved functional performance can be a major determinant of evolutionary changes in plants; however, there are structural and development limits to functional improvement, and once these are reached, the structure in question may no longer figure strongly in selection until and unless a new innovation evolves. The Silurian-Devonian paleobotanical record is consistent with the hypothesis that the succession of lowland floodplain dominants preserved in the fossil record of this interval was determined principally by the repeated evolution of new taxa that rose to ecological importance because of competitive advantages conferred by improved biophysical performance. This does not seem to be equally true for Carboniferous-Jurassic dominants of swamp and lowland floodplain environments. In these cases, environmental disruption appears to have been a major factor in shaping the fossil record. This does not mean that continuing adaptation was not important during this interval, but it may indicate that adaptive evolution was strongest in environments other than those best represented in the paleobotanical record.

NASA Discipline Exobiology↗

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

NASA Discipline Neuroscience↗

Are Soybean Models Ready for Climate Change Food Impact Assessments?

An accurate estimation of crop yield under climate change scenarios is essential to quantify our ability to feed a growing population and develop agronomic adaptations to meet future food demand. A coordinated evaluation of yield simulations from process-based eco-physiological models for climate change impact assessment is still missing for soybean, the most widely grown grain legume and the main source of protein in our food chain. In this first soybean multi-model study, we used ten prominent models capable of simulating soybean yield under varying temperature and atmospheric CO 2 concentration [CO 2 ] to quantify the uncertainty in soybean yield simulations in response to these factors. Models were first parametrized with high quality measured data from five contrasting environments. We found considerable variability among models in simulated yield responses to increasing temperature and [CO 2 ]. For example, under a + 3 °C temperature rise in our coolest location in Argentina, some models simulated that yield would reduce as much as 24%, while others simulated yield increases up to 29%. In our warmest location in Brazil, the models simulated a yield reduction ranging from a 38% decrease under + 3 °C temperature rise to no effect on yield. Similarly, when increasing [CO 2 ] from 360 to 540 ppm, the models simulated a yield increase that ranged from 6% to 31%. Model calibration did not reduce variability across models but had an unexpected effect on modifying yield responses to temperature for some of the models. The high uncertainty in model responses indicates the limited applicability of individual models for climate change food projections. However, the ensemble mean of simulations across models was an effective tool to reduce the high uncertainty in soybean yield simulations associated with individual models and their parametrization. Ensemble, ensemble mean yield responses to temperature and [CO 2 ] were similar to those reported from the literature. Our study is the first demonstration of the benefits achieved from using an ensemble of grain legume models for climate change food projections, and highlights that further soybean model development with experiments under elevated [CO 2 ] and temperature is needed to reduce the uncertainty from the individual models.

Agricultural Model Inter-comparison and Improvemen↗

Sensory-Motor Adaptation to Space Flight: Human Balance Control and Artificial Gravity

Gravity, which is sensed directly by the otolith organs and indirectly by proprioceptors and exteroceptors, provides the CNS a fundamental reference for estimating spatial orientation and coordinating movements in the terrestrial environment. The sustained absence of gravity during orbital space flight creates a unique environment that cannot be reproduced on Earth. Loss of this fundamental CNS reference upon insertion into orbit triggers neuro-adaptive processes that optimize performance for the microgravity environment, while its reintroduction upon return to Earth triggers neuro-adaptive processes that return performance to terrestrial norms. Five pioneering symposia on The Role of the Vestibular Organs in the Exploration of Space were convened between 1965 and 1970. These innovative meetings brought together the top physicians, physiologists, and engineers in the vestibular field to discuss and debate the challenges associated with human vestibular system adaptation to the then novel environment of space flight. These highly successful symposia addressed the perplexing problem of how to understand and ameliorate the adverse physiological effects on humans resulting from the reduction of gravitational stimulation of the vestibular receptors in space. The series resumed in 2002 with the Sixth Symposium, which focused on the microgravity environment as an essential tool for the study of fundamental vestibular functions. The three day meeting included presentations on historical perspectives, vestibular neurobiology, neurophysiology, neuroanatomy, neurotransmitter systems, theoretical considerations, spatial orientation, psychophysics, motor integration, adaptation, autonomic function, space motion sickness, clinical issues, countermeasures, and rehabilitation. Scientists and clinicians entered into lively exchanges on how to design and perform mutually productive research and countermeasure development projects in the future. The problems posed by long duration missions dominated these discussions and were driven by the paucity of data available. These issues along with more specific recommendations arising from the above discussions will be addressed an upcoming issue of the Journal of Vestibular Research.

Paloski, William H.↗

Modelling the Future Hydroclimatology of the Lower Fraser River and its Impacts on the Spawning Migration Survival of Sockeye Salmon

Short episodic high temperature events can be lethal for migrating adult Pacific salmon (Oncorhynchus spp.). We downscaled temperatures for the Fraser River, British Columbia to evaluate the impact of climate warming on the frequency of exceeding thermal thresholds associated with salmon migratory success. Alarmingly, a modest 1.0 C increase in average summer water temperature over 100 years (1981-2000 to 2081-2100) tripled the number of days per year exceeding critical salmonid thermal thresholds (i.e. 19.0 C). Refined thresholds for two populations (Gates Creek and Weaver Creek) of sockeye salmon (Oncorhynchus nerka) were defined using physiological constraint models based on aerobic scope. While extreme temperatures leading to complete aerobic collapse remained unlikely under our warming scenario, both populations were increasingly forced to migrate upriver at reduced levels of aerobic performance (e.g. in 80% of future simulations, => 90% of salmon encountered temperatures exceeding population specific thermal optima for maximum aerobic scope; T(sub opt)) = 16.3 C for Gates Creek and T(sub sopt)=14.5 C for Weaver Creek). Assuming recent changes to river entry timing persist, we also predicted dramatic increases in the probability of freshwater mortality for Weaver Creek salmon due to reductions in aerobic, and general physiological, performance (e.g. in 42% of future simulations =>50% of Weaver Creek fish exceeded temperature thresholds associated with 0 - 60% of maximum aerobic scope). Potential for adaptation via directional selection on run-timing was more evident for the Weaver Creek population. Early entry Weaver Creek fish experienced 25% (range: 15 - 31%) more suboptimal temperatures than late entrants, compared with an 8% difference (range: 0 - 17%) between early and late Gates Creek fish. Our results emphasize the need to consider daily temperature variability in association with population-specific differences in behaviour and physiological constraints when forecasting impacts of climate change on migratory survival of aquatic species.

Hague, M. J.↗

Countermeasure development to space adaptation

At the Johnson Space Center we are actively involved, with the collaboration of other NASA Centers and the scientific community at large, in the search for ways to counter the negative affects of spaceflight beginning with the improvement in our understanding of the adaptation. Heretofore this search will be broadly referred to as countermeasures development and includes not only the preservation of physiological well-being but also pyschological well-being. The psychological integrity of crews will, undoubtedly, become progressively more important as lengths, remoteness, and risks of missions increase. The character and priorities of our contermeasure development is very much dependent upon the character of the mission and requires a very close liaison between Medical Operations and the investigators. Because of the demands which countermeasure implementation imposes upon crew schedules and because of the potential weight, power, and budget impacts of the hardware and its development, a countermeasure can only become operational when it is either adequately validated or the human risk of not applying the existing technology exceeds the other negative impacts not directly related to crew health and safety.

Larochelle, F. T.↗

Physics, chemistry and pulmonary sequelae of thermodegradation events in long-mission space flight

An event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom is considered experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity enviroment impacts various stages of event simulation. Vapor-phase and particulate thermodegradation products were considered as potential spacecraft contaminants. A potential pathway for the production of ultrafine particles was identified. Different approaches to the simulation and prediction of contaminant transport were studied and used to predict the distribution of generic vapor-phase products in a Space Station model. A lung transport model was used to assess the pulmonary distribution of inhaled particles, and, finally, the impact of adaptation to low gravity on the human response to this inhalation risk was explored on the basis of known physiological modifications of the immune, endocrine, musculoskeletal and pulmonary systems that accompany space flight.

Todd, Paul↗

Otolith-Canal Convergence in Vestibular Nuclei Neurons

During manned spaceflight, acute vestibular disturbances often occur, leading to physical duress and a loss of performance. Vestibular adaptation to the weightless environment follows within two to three days yet the mechanisms responsible for the disturbance and subsequent adaptation are still unknown In order to understand vestibular system function in space and normal earth conditions the basic physiological mechanisms of vestibular information co coding must be determined. Information processing regarding head movement and head position with respect to gravity takes place in the vestibular nuclei neurons that receive signals From the semicircular canals and otolith organs in the vestibular labyrinth. These neurons must synthesize the information into a coded output signal that provides for the head and eye movement reflexes as well as the conscious perception of the body in three-dimensional space The current investigation will for the first time. determine how the vestibular nuclei neurons quantitatively synthesize afferent information from the different linear and angular acceleration receptors in the vestibular labyrinths into an integrated output signal. During the second year of funding, progress on the current project has been focused on the anatomical orientation of semicircular canals and the spatial orientation of the innervating afferent responses. This information is necessary in order to understand how vestibular nuclei neurons process the incoming afferent spatial signals particularly with the convergent otolith afferent signals that are also spatially distributed Since information from the vestibular nuclei is presented to different brain regions associated with differing reflexive and sensory functions it is important to understand the computational mechanisms used by vestibular neurons to produce the appropriate output signal.

Dickman, J. David↗

N(N)-nicotinic blockade as an acute human model of autonomic failure

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Non-NASA Center↗