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All sources NASA NTRS DOE OSTI

DOE OSTI2020

A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

ABSTRACT The Shox2 homeodomain transcriptional regulator is known for its critical functions during mouse embryogenesis, enabling accurate development of limbs, craniofacial structures, neural populations and the cardiac conduction system. At the genomic level, the Shox2 gene is flanked by an extensive gene desert, a continuous non-coding genomic region spanning over 500 kilobases that contains a multitude of evolutionarily conserved elements with predicted cis -regulatory activities. However, the transcriptional enhancer potential of the vast majority of these elements in combination with the biological necessity of the gene desert have not yet been explored. Using transgenic reporter assays in mouse embryos to validate an extensive set of stringent epigenomic enhancer predictions, we identify several novel gene desert enhancers with distinct tissue-specific activities in Shox2 expressing tissues. 4C-seq chromatin conformation capture further uncovers a repertoire of gene desert enhancers with overlapping activities in the proximal limb, in a compartment essential for Shox2 -mediated stylopod formation. Leveraging CRISPR/Cas9 to delete the gene desert region contained in the Shox2 topologically associated domain (TAD), we demonstrate that this complex cis -regulatory platform is essential for embryonic survival and required for control of region-specific Shox2 expression in multiple developing tissues. While transcription of Shox2 in the embryonic limb is only moderately affected by gene desert loss, Shox2 expression in craniofacial and cardiac domains is nearly abolished. In particular, Shox2 transcripts in the sinus venosus (SV) encompassing the sinoatrial node (SAN) were depleted in embryos lacking the gene desert, likely accounting for the embryonic lethality due to Shox2 -dependency of the SAN pacemaker. Finally, we discover a 1.5kb SV enhancer within the deleted gene desert region, which may act as a genomic module controlling the development of the cardiac conduction system. In summary, our results identify a gene desert indispensable for pleiotropic patterning and highlight the importance of these extensive regulatory landscapes for embryonic development and viability.

Abassah-Oppong, Samuel↗

DOE OSTI2020

ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function

Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the cis-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified. Here, to define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2001

A New Frontier for Cardiac Monitoring

CardioDynamics International Corporation (CDIC) has created the BioZ(TM) System through a Small Business Innovation Research (SBIR) award from Johnson Space Center, providing patients and physicians with a cost-effective and highly accurate monitoring system.The BioZ non-invasive heart monitor is based on a technology known as Impedance Cardiography (ICG). BioZ provides the physician with vital information about the heart's ability to deliver blood to the body, the force one's heart exerts with each beat, and the amount of fluid in the chest. Specially designed bioimpedance sensors placed on the neck and chest monitor 12 different parameters, including cardiac output, contractility, systemic vascular resistance, and thoracic fluid content. These sensors monitor the electrical conductivity of the body-information that is converted into blood flow data and is displayed in real time on a monitoring screen. BioZ.com(TM) and BioZ.pc(TM) are two additional products that incorporate the same sensors present in the original BioZ system. The "com" in BioZ.com stands for cardiac output monitor. This fully integrated system is essentially a smaller version of the BioZ, combining the same abilities with a compact, lightweight design, while providing greater portability.

Source record↗

NASA NTRS1999

Cardiovascular Deconditioning in Humans: Human Studies Core

Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

Williams, Gordon↗

NASA NTRS1991

Gravitational force and the cardiovascular system

Ground-based simulation studies have been conducted to clarify the problems of the cardiovascular adaptation to alterations in gravitational force. Simulated microgravity experiments resulted in increases in cardiac stretch, urine flow, and sodium excretion, which were accompanied by lower plasma renin, aldosterone, and ADH. There appears to be a decrease in plasma volume as well as in sympathetic tone after 2-3 days of 0 Gz. Complete adjustment to 0 Gz is found within 8 h without a decrease in plasma volume, when subjects are allowed to dehydrate mildly.

Pendergast, D. R.↗

NASA NTRS2017

Risk of Cardiac Rhythm Problems During Spaceflight

NASA has concerns regarding the incidence and clinical significance of cardiac arrhythmias that could occur during long-term exposure to the spaceflight environment, such as on the International Space Station (ISS) or during a prolonged (e.g., up to 3 years) sojourn to Mars or on the Moon. There have been some anecdotal reports and a few documented cases of cardiac arrhythmias in space, including one documented episode of non-sustained ventricular tachycardia. The potential catastrophic nature of a sudden cardiac death in the remote space environment has led to concerns from the early days of the space program that spaceflight might be arrhythmogenic. Indeed, there are known and well-defined changes in the cardiovascular system with spaceflight: a) plasma volume is reduced, b) left ventricular mass is decreased, and c) the autonomic nervous system adapts to the weightless environment. Combined, these physiologic adaptations suggest that changes in cardiac structure and neuro-humoral environment during spaceflight could alter electrical conduction, although the evidence supporting this contention consists mostly of minor changes in QT interval (the time between the start of the Q wave and the end of the T wave on an electrocardiogram tracing) in a small number of astronauts after long-duration spaceflight. Concurrent with efforts by NASA Medical Operations to refine and improve screening techniques relevant to arrhythmias and cardiovascular disease, as NASA enters the era of exploration-class missions it will be critical to determine with the highest degree of certainty whether spaceflight by itself alters cardiac structure and function sufficiently to increase the risk of arrhythmias.

Lee, Stuart M. C.↗

NASA NTRSDate not supplied

Bion-M2

Bion-M2, scheduled to launch in April 2023, continues the 30+ year collaboration between the Institute of Biomedical Problems of the Russian Academy of Sciences (IBMP RAS) and the National Aeronautics and Space Administration (NASA). Bion-M2 is the second biosatellite in the Bion-M series and its goal is to investigate how the space environment affects living organisms, with emphasis on physiological changes in rodents, gravitational biology using a wide variety of specimens, and radiation biology. The Bion-M2 biosatellite will complete a 30-day low earth orbit (LEO) flight to study the combined effects of microgravity and ionizing radiation (IR) on multiple organisms, where the payload may be exposed to IR at 20-30 times thedose rate seen on the International Space Station. Following return, nine U.S. collaborators selected through the NASA Space Biology Research Announcement will conduct post-flight rodent experiments using male C57BL/6 mice. The post-flight experiments will investigate the effects of the space environment on bone and skeletal muscle health, cardiac function, reproductive system function, neurovascular systems, protein composition in plasma, and thermoregulation in the mice. Currently, the Bion-M2 mission is in the development phase of theproject lifecycle. The mission objectives, constraints, requirements, and timeline have been defined in the project plan and contracts. Technology for the mission is under development and science procedures will be finalized by FY22. The aim of this presentation is to highlight the importance of the Bion-M2 mission and provide insight into the mission development process, including an overview of the project plan and the tissue sharing plan that will be utilized during the post-flight dissection procedures.

Bion-M2↗

NASA NTRS2016

NASA'S Standard Measures During Bed Rest: Adaptations in the Cardiovascular System

Bed rest is a well-accepted analog of space flight that has been used extensively to investigate physiological adaptations in a larger number of subjects in a shorter amount of time than can be studied with space flight and without the confounding effects associated with normal mission operations. However, comparison across studies of different bed rest durations, between sexes, and between various countermeasure protocols have been hampered by dissimilarities in bed rest conditions, measurement protocols, and testing schedules. To address these concerns, NASA instituted standard bed rest conditions and standard measures for all physiological disciplines participating in studies conducted at the Flight Analogs Research Unit (FARU) at the University of Texas-Medical Branch. Investigators for individual studies employed their own targeted study protocols to address specific hypothesis-driven questions, but standard measures tests were conducted within these studies on a non-interference basis to maximize data availability while reducing the need to implement multiple bed rest studies to understand the effects of a specific countermeasure. When possible, bed rest standard measures protocols were similar to tests nominally used for medically-required measures or research protocols conducted before and after Space Shuttle and International Space Station missions. Specifically, bed rest standard measures for the cardiovascular system implemented before, during, and after bed rest at the FARU included plasma volume (carbon monoxide rebreathing), cardiac mass and function (2D, 3D and Doppler echocardiography), and orthostatic tolerance testing (15- or 30-minutes of 80 degree head-up tilt). Results to-date indicate that when countermeasures are not employed, plasma volume decreases and the incidence of presyncope during head-up tilt is more frequent even after short-duration bed rest while reductions in cardiac function and mass are progressive as bed rest duration increases. Additionally, while plasma volume loss can be corrected and cardiac mass can be prevented with properly applied countermeasures, orthostatic tolerance is more difficult to protect when supine exercise is the only countermeasure. Similar results have been observed after space flight. Plasma volume, cardiac chamber volume, and orthostatic tolerance recover relatively quickly with resumption of ambulation and normal activity levels after bed rest but restoration of cardiac mass is prolonged.

Lee, Stuart M. C.↗

NASA NTRS1999

Alterations in Cardiovascular Regulation and Function During Long-Term Simulated Microgravity

The Cardiovascular Alterations Team is conducting studies of hemodynamic regulation and susceptibility to arrhythmias resulting from sixteen days of simulated microgravity exposure. In these studies very intensive measurements are made during a short duration of bed rest. In this collaborative effort are making many of the same measurements, however much less frequently, on subjects who are exposed to a much longer duration of simulated microgravity. Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In addition, numerous reports from the past 30 years suggest that the incidence of ventricular arrhythmias among astronauts is increased during space flight. However, the effects of space flight and the associated physiologic stresses on cardiac conduction processes are not known, and an increase in cardiac susceptibility to arrhythmias has never been quantified. In this project we are applying the most powerful technologies available to determine, in a ground-based study of long duration space flight, the mechanisms by which space flight affects cardiovascular function, and then on the basis of an understanding of these mechanisms to develop rational and specific countermeasures. To this end we are conducting a collaborative project with the Bone Demineralization/Calcium Metabolism Team of the National Space Biomedical Research Institute (NSBRI). The Bone Team is conducting bed rest studies in human subjects lasting 17 weeks, which provides a unique opportunity to study the effects of long duration microgravity exposure on the human cardiovascular system. We are applying a number of powerful new methods to these long term bed rest subjects, including cardiovascular system identification (CSI), microvolt level T wave alternans analysis, and cardiac magnetic resonance imaging to assess non-invasively the effects of simulated long duration space flight on the cardiovascular system.

Cohen, Richard J.↗

NASA NTRS2004

Detection and Prevention of Cardiac Arrhythmias During Space Flight

There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.

Pillai, Dilip↗

NASA NTRS1976

Biomedical technology transfer: Applications of NASA science and technology

The major efforts of the Stanford Biomedical Applications Team Program at the Stanford University School of Medicine for the period from October 1, 1975 to September 31, 1976 are covered. A completed EMG biotelemetry system which monitors the physiological signals of man and animals in space related research is discussed. The results of a pilot study involving lower body negative pressure testing in cardiac patients has been completed as well as the design and construction of a new leg negative pressure unit for evaluating heart patients. This technology utilizes vacuum chambers to stress the cardiovascular system during space flight. Laboratory tests of an intracranial pressure transducer, have been conducted. Extremely stable long term data using capacative pressure sensors has lead to the order of commercially manufactured monitoring systems base. Projects involving commercialization are: flexible medical electrodes, an echocardioscope, a miniature biotelemetry system, and an on-line ventricular contour detector.

Source record↗

NASA NTRS1976

Biomedical technical transfer. Applications of NASA science and technology

Lower body negative pressure testing in cardiac patients has been completed as well as the design and construction of a new leg negative unit for evaluating heart patients. This technology is based on NASA research, using vacuum chambers to stress the cardiovascular system during space flight. Additional laboratory tests of an intracranial pressure transducer, have been conducted. Three new biomedical problems to which NASA technology is applicable are also identified. These are: a communication device for the speech impaired, the NASA development liquid-cooled garment, and miniature force transducers for heart research.

Source record↗

NASA NTRS2002

Long-Duration Space Flight Provokes Pathologic Q-Tc Interval Prolongation

Space flight has a profound influence on the cardiovascular and autonomic nervous systems. Alterations in baroreflex function, plasma catecholamine concentrations, and arterial pressure regulation have been observed. Changes in autonomic regulation of cardiac function may lead to serious rhythm disturbances. In fact, ventricular tachycardia has been reported during long-duration space flight. The study aim was to determine the effects of space flight on cardiac conduction. Methods and Results: Electrocardiograms (ECGs) and serum electrolytes were obtained before and after short-duration (SD) (4-16 days) and long-duration (LD) (4-6 months) missions. Holter recordings were obtained from 3 different subjects before, during and after a 4-month mission. P-R, R-R, and Q-T intervals were measured manually in a random, blinded fashion and Bazzet's formula used to correct the Q-T interval (Q-Tc). Space flight had no clinically significant effect on electrolyte concentrations. P-R and RR intervals were decreased after SD flight (p<0.05) and recovered 3 days after landing. In the same subjects, P-R and Q-Tc intervals were prolonged after LD flight (p<0.01). Clinically significant Q-Tc prolongation (>0.44 sec) occurred during the first month of flight and persisted until 3 days after landing (p<0.01). Conclusions - Space flight alters cardiac conduction with more ominous changes seen with LD missions. Alterations in autonomic tone may explain ECG changes associated with space flight. Primary cardiac changes may also contribute to the conduction changes with LD flight. Q-Tc prolongation may predispose astronauts to ventricular arrhythmias during and after long-duration space flight.

D'Aunno, DOminick S.↗

NASA NTRSDate not supplied

Results of a 3-day Pilot Study to Validate Planetary Prebreathe Protocols Using a 56.5 kPa 34% O2, 66% N2 Saturation Cabin Atmosphere

INTRODUCTION: Apollo missions used 100% O2 cabin atmospheres which effectively eliminated the risk of decompression sickness (DCS) during extravehicular activities (EVAs, ‘spacewalks’); however, this atmosphere presented a flammability risk that is no longer acceptable to NASA. Denitrogenation prebreathe protocols used to mitigate DCS risk for Space Shuttle and International Space Station EVAs are validated for the microgravity environment, but the significantly increased risk of DCS during equivalent ambulatory surface EVAs make these protocols inapplicable to planetary/Lunar missions. An “exploration atmosphere” of 56.5 kPa (8.2 psia), 34% O2, 66% N2 has been recommended by NASA for future Moon and Mars missions as a compromise that balances subsequent pre-EVA prebreathe duration, hypoxia, and flammability risk, assuming a 29.6 kPa (4.3 psi) spacesuit. Prebreathe validation studies was initiated utilizing a three-story 6m diameter hypobaric chamber at NASA’s Johnson Space Center. Here, we report the results of a 3-day human-in-the-loop system checkout. METHODS: Six volunteers acclimated to the 56.6kPa/34% O2 66% N2 environment for 48hrs prior to conducting a 20-minute prebreathe and a 6-hour simulated EVA at 34kPa/85% O2 / 15% N2. The EVA simulation was designed to include tasks that are physically and ergonomically representative of future planetary EVAs. Decompression stress was evaluated by serial doppler and echocardiographs, as well as by clinical features of DCS signs/symptoms. RESULTS AND DISCUSSION: Preliminary data analysis noted venous gas emboli (VGE) in 3 of 6 subjects, with peak Grade II VGE by Doppler and peak E-B score of 5 by cardiac ultrasonography. No volunteers were diagnosed with DCS during this initial test. No acute hypoxic symptoms were noted. Musculoskeletal and gastrointestinal complaints were noted, likely associated with the exercise load and the food system. Validation of exploration prebreathe protocols has since been initiated with an 11-day saturation test using the same facility and protocol.

Alejandro Garbino↗

NASA NTRS2015

Lunar Health Monitor (LHM)

Orbital Research, Inc., has developed a low-profile, wearable sensor suite for monitoring astronaut health in both intravehicular and extravehicular activities. The Lunar Health Monitor measures respiration, body temperature, electrocardiogram (EKG) heart rate, and other cardiac functions. Orbital Research's dry recording electrode is central to the innovation and can be incorporated into garments, eliminating the need for conductive pastes, adhesives, or gels. The patented dry recording electrode has been approved by the U.S. Food and Drug Administration. The LHM is easily worn under flight gear or with civilian clothing, making the system completely versatile for applications where continuous physiological monitoring is needed. During Phase II, Orbital Research developed a second-generation LHM that allows sensor customization for specific monitoring applications and anatomical constraints. Evaluations included graded exercise tests, lunar mission task simulations, functional battery tests, and resting measures. The LHM represents the successful integration of sensors into a wearable platform to capture long-duration and ambulatory physiological markers.

Lisy, Frederick J.↗

NASA NTRS2018

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified.

Portable Pulmonary Function System (PPFS)↗

NASA NTRSDate not supplied

Mitigating Headward Fluid Shifts with Venoconstrictive Thigh Cuffs during Spaceflight

Venoconstrictive thigh cuffs (VTC) are a mechanical countermeasure capable of attenuating the spaceflight induced headward fluid shift, and thus may be a viable spaceflight associated neuro-ocular syndrome (SANS) countermeasure. Crewmembers can use VTC to mitigate the headward fluid shift to aid in adapting to spaceflight. However, data are needed to determine if VTC affect ocular structures. PURPOSE The purpose of this study is to determine the efficacy of long duration use of VTC application to mitigate the spaceflight-induced headward fluid shift. We hypothesize that a VTC countermeasure will temporarily reverse the headward fluid shift and attenuate spaceflight-induced changes of internal jugular vein (IJV) cross-sectional area, IJV pressure, stroke volume, cardiac output, intraocular pressure (IOP), and optic nerve head and retinal morphology. METHODS This study will evaluate the effectiveness of VTC countermeasure application on the headward fluid shift, as well as cardiovascular and ocular variables. VTC during spaceflight will be worn for an extended duration (up to 6 hours) with data collected at three time points (30 minutes, 3 hours, and 6 hours) to characterize the temporal profile of key fluid shift outcome measures of the vascular fluid shift, IOP, and ocular structure changes. Ten astronauts will be recruited to participate and will be studied before and during approximately 180-day International Space Station (ISS) spaceflight missions. Baseline data collection will occur approximately 90-days before launch (Figure). Preflight, each leg of the crewmember will be measured to determine the VTC cuff size and a cuff fit check session will occur prior to the preflight baseline ground imaging to verify the appropriate fit measured via a surface contact pressure. Prior to donning the VTC, baseline measures without VTC will be collected seated, supine, and supine followed by data collection with the VTC. The baseline data collection will include ultrasound (IJV area and pressure, stroke volume and cardiac output), brachial blood pressure and heart rate, optical coherence tomography (OCT) imaging (total retinal thickness and choroid thickness), and IOP. An inflight cuff fit check session, same as the preflight fit check, will occur prior to VTC use on ISS. The inflight VTC experiment will be conducted early (FD45) and late (R-45) to determine if mission duration affects VTC fit and the efficacy of fluid redistribution. A system usability scale comfort questionnaire will be included in each VTC session to capture feedback from crewmembers regarding the comfort and usability of the VTC. SCIENTIFIC & MISSION IMPACT Results will narrow knowledge gaps described in the Human Research Roadmap to mitigate the headward fluid shift during spaceflight and help NASA to 1) determine the efficacy of extended use VTC application to mitigate the spaceflight-induced headward fluid shift and 2) further the understanding of the use of VTC on vascular fluid shifts, IOP, and ocular structure during spaceflight. Supported by NASA Human Research Program Directed Research. Figure. Detailed Testing Schedule. Baseline data collection at L-90 will be performed in a randomized order of position.

J V Jasien↗

NASA NTRS1996

Animal models and their importance to human physiological responses in microgravity

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

NASA Discipline Cardiopulmonary↗