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NASA NTRS1982

Changes in blood volume and response to vaso-active drugs in horizontally casted primates

Experiments were performed on horizontally casted primates (male rhesus monkeys) in order to note changes in blood volume caused by horizontal restraint, to compare orthostatic tolerance before and after casting using the responses to upright tilting, to begin to uncover the cardiovascular and neural mechanisms involved in deconditioning, and to compare the data with that obtained from bed-rested human subjects and from humans exposed to weightlessness. Bolus injections of norepinephrine of 2.0 microgram/kg, phenylephrine of 4.0 microgram/kg, and nitroprusside of 2.0 microgram/kg were administered; and aortic pressure and heart rate were recorded during the injections. The results indicate that the horizontally casted primate is a valid animal model for studying the effects of simulated zero-G on the human cardiovascular system.

Dickey, D. T.↗

NASA NTRS1982

Short term /1 and 3 day/ cardiovascular adjustments to suspension antiorthostasis in rats

Antiorthostasis (AO) results in responses reflective of thoracic vessel loading. Initial findings included fluid and electrolyte shifts (diuresis and natriuresis) in AO but not in orthostatic (O) rats. This study aims at obtaining supportive evidence for cardiovascular responses, E.g., blood pressure and related parameters, in light of the original hypothesis. Tilting rats rapidly head-up from either horizontal (O) or head-down (AO) positions was used to assess cardiovascular sensitivities. O and AO rats were used after 1 or 3 days of suspension. Rats were controls (C), pre-tilted O and AO, tilted O and AO (rapid head-up 70-80 deg); post-tilted (to original postures). MAP in C rats was 108 +2 mmHg, in O, (117 + or - 1.02) and AO, (120 + or - 0.58). MAP, diastolic pressure (DP) and pulse pressure were consistently elevated in AO rats on day 3. With rapid head-up tilt, only MAP and DP showed significant increases. These changes were seen as cardiovascular responses to AO and support further use of this rat model for AO studies.

Musacchia, X. J.↗

NASA NTRS1991

Proceedings of the First Joint NASA Cardiopulmonary Workshop

The topics covered include the following: flight echocardiography, pulmonary function, central hemodynamics, glycerol hyperhydration, spectral analysis, lower body negative pressure countermeasures, orthostatic tolerance, autonomic function, cardiac deconditioning, fluid and renal responses to head-down tilt, local fluid regulation, endocrine regulation during bed rest, autogenic feedback, and chronic cardiovascular measurements. The program ended with a general discussion of weightlessness models and countermeasures.

Fortney, Suzanne M.↗

NASA NTRS2010

Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

Sundaresan, Alamelu↗

NASA NTRS2019

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↗

NASA NTRSDate not supplied

Evaluation of Aerosol Data Assimilation and Forecasts in the NASA GEOS Model during the ASIA-AQ Campaign

Fine particulate matter (PM2.5) poses significant risks to human health and the environment by penetrating the lungs and causing respiratory and cardiovascular diseases, making it crucial to understand its sources and behavior for effective air quality management. The Goddard Earth Observing System (GEOS) Forward Processing (FP) system model, operated by the Global Modeling and Assimilation Office (GMAO) at NASA's Goddard Space Flight Center, provides real-time weather and aerosol analyses and forecasts. In addition to meteorological data assimilation, the GEOS-FP system also assimilates aerosol using Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth (AOD) and Aerosol Robotic Network (AERONET) AOD data. In this study, the aerosol data assimilation and forecasts performance of the GEOS-FP model were evaluated for predicting PM2.5 in Korea using observations from the Airborne and Satellite Investigation of Asian Air Quality (ASIA-AQ) campaign. The ASIA-AQ campaign, an international collaborative field study initiative, aims to enhance understanding of local air quality issues and address common challenges in interpreting satellite data and air quality modeling. Conducted in South Korea from February 15 to March 13, 2024, during the high PM2.5 concentration winter season, this campaign provided extensive airborne and ground observations for intensive analysis of PM2.5 model simulations. We demonstrate how the assimilation runs and the forecasting performance of PM2.5 at 24-hour and 48-hour intervals vary. Additionally, we analyzed the differences and characteristics of PM2.5 composition in cases of long-range transport and local emissions. Using ASIA-AQ airborne data, we also examined the vertical profile of fine particulate matter. Through the intensive observations of this campaign, the GEOS model was assessed over South Korea using both in situ and airborne measurements to establish a baseline and identify priorities for future development.

Seunghee Lee↗

NASA NTRS1996

Cardiovascular Deconditioning and Venous Air Embolism in Simulated Microgravity in the Rat

Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

Robinson, R. R.↗

NASA NTRS2011

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.↗

NASA NTRS2011

Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

Hu, Shaowen↗

NASA NTRS2019

Investigating Neuro-Consequences of Spaceflight Using Drosophila Melanogaster

Research on human acclimation to spaceflight, including the recent NASA's Twin Study, reports complex effects of the spaceflight environment on health, with both acute and prolonged changes in multiple tissues. Spaceflight includes multiple factors such as microgravity, ionizing radiation, physiological stress, and disrupted circadian rhythms, that have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes on the nervous system. With 75% disease gene orthology to humans, short generation time, large sample size and ease of genetic, neuronal and behavioral studies, Drosophila is an excellent model to study nervous system dysfunction. Here, we present results from MVP-Fly-01 spaceflight mission that was launched on SpaceX CRS-14. The MVP hardware (developed by Techshot) used in this mission enabled us to have an in-flight 1g centrifuge, to distinguish the changes resulting from gravity versus those induced by other environmental factors associated with spaceflight. We observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown microgravity adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001) compared to in-flight 1g controls, suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.

Iyer, Janani↗

NASA NTRS2024

Crew State and Risk Model Development to Predict Hydration Status During Extravehicular Activity Training Events

Introduction: Hydration is critical for optimal human health and performance and dehydration can lead to impaired cardiovascular function, thermal dysregulation, decreased blood plasma volume, and cognitive impacts, particularly during physical activity. Prolonged and repeated extravehicular activities (EVA) without sufficiently available drinking water may increase risk for dehydration, which could impair crew health and impact mission success. Understanding hydration needs and potential effects on health and performance are necessary to optimize crew well-being and enable successful EVA objectives. This study aims to develop a model of hydration status during EVA using water balance techniques. Methods: Water balance measures were collected on 15 healthy astronauts who performed ≈6-hour simulated microgravity extravehicular activity (EVA) training in the NASA Neutral Buoyancy Laboratory (NBL). Data collected included pre-and post-EVA nude body weight (BW), maximum absorption garment (MAG) weight, Disposable In-suit Drink Bag (DIDB) weight, urine specific gravity (USG), and extra pre-EVA intake (W). Variables were combined to create the water balance model as pre-EVA (Hn)= BWn+ MAGn+ DIDBn+ Wnand post EVA (Hn+1) = BWn+1+ MAGn+1+ DIDBn+1. Urine specific gravity values were used to refine water balance measures into hydration categories: Hydrated, Marginally Hydrated, and Dehydrated. Results: Pre-EVA modeling indicated53% of crew were hydrated, 20% were marginally hydrated, and 27% were dehydrated. Alternately, Hn+1 showed 13% of crew remained hydrated, 47% were marginally hydrated, and 40% were dehydrated at the end of the EVA. Furthermore, 75% of the crewmembers who started sufficiently hydrated finished the run marginally hydrated or dehydrated. According to USG indices presented by Casa and Lawrence, et al. (2000), only 25% of the crew started and remained hydrated throughout the EVA, and those who were dehydrated at the outset stayed dehydrated. Conclusion: Model outcomes assessing hydration status during 6-hour simulated microgravity EVAs demonstrate the necessity to further address hydration requirements for optimal human performance during spaceflight and EVA. This study enables additional baseline development of the Crew State and Risk Model Hydration, Nutrition, and Waste Management component that aims to provide individualized crew state and risk predictions during EVAs. Reference: Casa, D. J., Armstrong, L. E., et al. (2000). National Athletic Trainers’ Association Position Statement: Fluid Replacement for Athletes. Journal of Athletic Training, 35:212-224.

L Cooper↗

NASA NTRSDate not supplied

Watching Without Seeing a Tool to Surveil Astronaut Health Outcomes While Maintaining Astronaut Medical Privacy

BACKGROUND The Privacy Act of 1974 regulates the use a nd disclosure of personally identifiable information by US Federal agencies. The Act applies to biographical, financial, a nd other identity-linked information, a s well a s personal health information (PHI). As such, the use of astronaut PHI is limited to authorized personnel for preapproved uses, with data reporting often limited to aggregated information about groups. These limitations on the use a nd reporting of astronaut PHI complicates surveillance efforts, wherein epidemiologists a t the National Aeronautics and Space Administration (NASA)monitor the incidence of targeted health conditions in the astronaut population, or to discover emerging trends of aging and disease. Stratification on one or more covariates –particularly time-period, sex, a nd mission participation –can lead to extremely small datasets such that the reporting of results is potentially attributable to individuals. An additional challenge is the small size of the astronaut population, both in terms of numbers of individuals a s well a s in terms of density of exposure time. Such small datasets yield volatile rate estimates that are difficult to interpret. To a id the epidemiological surveillance efforts, a surveillance tool is required that can (a) satisfy the need for rapid computation of condition-specific incidence and mortality rates; (b) improve the statistical estimates of these estimated rates; and (c) maintain astronaut privacy. Here we describe a nd demonstrate such a tool. METHODS We devised a system that models incidence a nd mortality rates rather than calculating them directly. This ha s the advantage of using all the available data to derive the estimates, lea ding to rates that a re not attributable to any one individual, a nd a re a s numerically stable a s they can be given the extremely limited data. The system models disease endpoints using a Poisson regression model with exposure density (measured in person-years) a s a n offset term. By doing so the model is estimating event counts per person-year, equivalent to modeling the rates directly. It uses a standard (pre-specified)set of covariates; the system does not engage in “model-building” as model parsimony is not the goa l. Instead, it is explicitly recognized that if a covariate is not statistically significant a nd not a confounder then it will likely have very little effect on the estimate of the incidence a nd mortality rates. Users are able to specify the disease endpoint of interest and the covariates over which they would like to stratify. The system then uses the resulting model to compute the estimated rates for the user-chosen configuration of variables as visualizes those either over an age range within a specified time-period, or over time for astronauts with a specified age range. RESULTS The first iteration of the tool computes incidence a nd mortality rates for cardiovascular conditions and cancers. Code ha s been developed to retrieve the appropriate data from the IMPALA analysis platform, compute the models for incidence a nd mortality, a nd then use those models to generate the corresponding rate curves. A companion graphical user interface allows the user to specify the curves and visualize the results. CONCLUSIONS It is important to note that the rapid surveillance tool described here is neither meant to be a definitive assessment of the incidence or mortality of any particular disease or condition in the astronaut population, nor is it meant to be used for research purposes. Rather, it is meant as an early indicator that in-depth investigation may be warranted. By automating a repetitive process and leveraging carefully curated astronaut health outcomes, the tool makes possible a rapid “first look” into known areas of concern, and, if used judiciously, may surface new areas of concern for long-term astronaut health. This work is supported in part by the Translational Research Institute for Space Health (TRISH) through NASA Cooperative Agreement NNX16AO69A.

R J Reynolds↗

NASA NTRS1992

USSR Space Life Sciences Digest, issue 32

This is the thirty-second issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 34 journal or conference papers published in Russian and of 4 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, aviation medicine, biological rhythms, biospherics, cardiovascular and respiratory systems, developmental biology, exobiology, habitability and environmental effects, human performance, hematology, mathematical models, metabolism, microbiology, musculoskeletal system, neurophysiology, operational medicine, and reproductive system.

Stone, Lydia Razran↗

NASA NTRS1994

Comparison of cardiovascular function during the early hours of bed rest and space flight

This paper reviews the cardiovascular responses of six healthy male subjects to 6 hours in a 5 degrees head-down bed rest model of weightlessness, and compares these responses to those obtained when subjects were positioned in head-up tilts of 10 degrees, 20 degrees, and 42 degrees, simulating 1/6, 1/3, and 2/3 G, respectively. Thoracic fluid index, cardiac output, stroke volume, and peak flow were measured using impedance cardiography. Cardiac dimensions and volumes were determined from two-dimensional guided M-mode echocardiograms in the left lateral decubitus position at 0, 2, 4, and 6 hours. Cardiovascular response to a stand test were compared before and after bed rest. The impedance values were related to tilt angle for the first 2 hours of tilt; however, after 3 hours, at all four angles, values began to converge, indicating that cardiovascular homeostatic mechanisms seek a common adapted state, regardless of effective gravity level (tilt angle) up to 2/3 G. Echocardiography revealed that left ventricular end-diastolic and end-systolic volume, stroke volume, ejection fraction, heart rate, and cardiac output had returned to control values by hour 6 for all tilt angles. The lack of a significant immediate change in left ventricular end-diastolic volume, despite decrements in stroke volume (P < .05) and heart rate (not significant), indicates that multiple factors may play a role in the adaptation to simulated hypogravity. The echocardiography data indicated that no angle of tilt, whether head-down or head-up for 4 to 6 hours, mimicked exactly the changes in cardiovascular function recorded after 4 to 6 hours of space flight. Changes in left ventricular end-diastolic volume during space flight and tilt may be similar, but follow a different time course. Nevertheless, head-down tilt at 5 degrees for 6 hours mimics some (stroke volume, systolic and diastolic blood pressure, mean arterial blood pressure, and total resistance), but not all, of the changes occurring in an equivalent time of space flight. The magnitude of the change in the mean heart rate response to standing was greater after six hours of tilt at -5 degrees or 10 degrees. Thus, results from the stand test after 6 hours of bed rest at -5 degrees and 10 degrees, but not at 20 degrees or 42 degrees, are similar to those obtained after space flight.

Space Flight↗

NASA NTRS1977

Application and effectiveness of prophylactic devices in model experiments

Material is presented for evaluating the effectiveness of prophylactic devices intended for maintaining: a relatively high functional level of the cardiovascular system; the nerve and muscle apparatus; and the water and salt status. The effects of the following are analyzed: physical training, lower body negative pressure, regulation of water and salt consumption, pharmacological preparations, and a combination of these. The author points out the need for further research.

Kakurin, L. I.↗

NASA NTRS2016

Human Health Countermeasures - Partial-Gravity Analogs Workshop

The experimental conditions that were deemed the most interesting by the HHC Element lead scientists are those permitting studies of the long-term effects of exposure to (a) chronic rotation when supine or in head down tilt (ground-based); and (b) long-radius centrifugation (space based). It is interesting to note that chronic ground based slow rotation room studies have not been performed since the 1960's, when the USA and USSR were investigating the potential use of AG for long-duration space missions. On the other hand, the other partial gravity analogs, i.e., parabolic flight, HUT, suspension, and short-radius centrifugation, have been regularly used in the last three decades (see review in Clément et al. 2015). Based on the workshop evaluations and the scores by the HHC scientific disciplines indicated in tables 3 and 4, simulation of partial G between 0 and 1 should be prioritized as follows: Priority 1. Chronic space-based partial-G analogs: a. Chronic space-based long-radius centrifugation. The ideal scenario would be chronic long-radius centrifugation of cells, animals and humans in a translational research approach - ideally beyond low earth orbit under deep space environmental effects and at various rotations - to obtain different G-effects. In this scenario, all physiological systems could be evaluated and the relationship between physiological response and G level established. This would be the most integrative way of defining, for the first time ever, G-thresholds for each physiological system. b. Chronic space-based centrifugation of animals. Chronic centrifugation of rodents at various G levels in space would allow for determination of AG thresholds of protection for each physiological system. In this case, all physiological systems will be of interest. Intermittent centrifugation will be of secondary interest. c. Chronic space-based centrifugation of cell cultures (RWV). Bioreactor studies of cells and cell cultures of various tissues at various G levels would allow for intracellular investigations of the effects of partial-G. Priority 2. Acute, intermittent space based partial-G analogs: a. Acute, intermittent space-based short radius human centrifugation. Intermittent centrifugation of humans would allow determination of thresholds of AG for protection of astronaut health in space. Priority 3. Chronic ground-based partial-G analogs: a. Chronic centrifugation of supine or head-down tilted humans. b. Chronic head-up tilt in humans. c. Chronic head-out graded dry immersion in humans. d. Chronic partial suspension of rodents e. Chronic rotating bioreactor cell culture studies (RWV) Priority 4. Acute ground based partial-G analogs. a. Parabolic flights. Very acute and short term effects of G levels between 0 and 1 in humans for fast responding systems like cardiovascular and sensorimotor as well as for acute responses in cell cultures and animals. b. Other acute models as indicated in table 3.

Barr, Yael↗

NASA NTRSDate not supplied

MicroRNA Based Countermeasure Rescue Health Risks Associated with Space Radiation and Microgravity

From our earlier work, we demonstrated a circulating microRNA (miRNA) signature that is present and involved with the general increased health risks during spaceflight. From this work we demonstrated that this miRNA signature impacted the overall biology and health with both the microgravity and space radiation components of the space environment. We showed that this miRNA signature can be an optimal biomarker for health risk and also has potential to be utilized as a countermeasure to mitigate the damage caused by the space environment by utilizing a human 3D microvascular tissue model. By applying a novel self-delivery system to target 3 miRNAs (i.e. antagomirs) from our spaceflight miRNA signature impacting cardiovascular health risks, we were able to completely mitigate damage caused by exposure to simulated Galactic Cosmic Ray (GCR) irradiation. Here we further expand on the countermeasure experiments to uncover the specific novel biology involved with this countermeasure and in vivo experiments that demonstrates that these antagomirs rescue damage caused to certain organs due to both microgravity and space radiation. Specifically, the miRNAs rescued damage to the heart and immune suppression that occurred in addition to other key biology. In addition, we have also observed with the 3D microvascular tissue model improved DNA double strand break repair machinery which can also contribute to improved recovery and protection against damage caused by space radiation. This work expands on our previous work and further uncovers how a potential minimally invasive countermeasure can be used to mitigate space environment effects.

Angela Kubik↗

NASA NTRSDate not supplied

microRNA Based Countermeasure Mitigate Health Risks Associated with Space Radiation and Microgravity

Afshin Beheshti↗