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NASA NTRS2002

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio-acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (+/- S.E.M.) heart rates before lower body suction were similar pre-flight and in flight. Heart rate responses to -30 mmHg were greater in flight (from 56 +/- 4 to 72 +/- 4 beats min(-1)) than pre-flight (from 56 +/- 4 at rest to 62 +/- 4 beats min(-1), P < 0.05). Noradrenaline spillover and clearance were increased from pre-flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post-flight days 1 or 2 (n = 5, P < 0.05). In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre-flight levels or higher in each subject (35 pre-flight vs. 40 bursts min(-1) in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic responses to lower body suction are exaggerated. Therefore, notwithstanding hypovolaemia, astronauts respond normally to simulated orthostatic stress and are able to maintain their arterial pressures at normal levels.

STS-90 Shuttle Project↗

NASA NTRS2014

A Case for Hypogravity Studies Aboard ISS

Future human space exploration missions being contemplated by NASA and other spacefaring nations include some that would require long stays upon bodies having gravity levels much lower than that of Earth. While we have been able to quantify the physiological effects of sustained exposure to microgravity during various spaceflight programs over the past half-century, there has been no opportunity to study the physiological adaptations to gravity levels between zero-g and one-g. We know now that the microgravity environment of spaceflight drives adaptive responses of the bone, muscle, cardiovascular, and sensorimotor systems, causing bone demineralization, muscle atrophy, reduced aerobic capacity, motion sickness, and malcoordination. All of these outcomes can affect crew health and performance, particularly after return to a one-g environment. An important question for physicians, scientists, and mission designers planning human exploration missions to Mars (3/8 g), the Moon (1/6 g), or asteroids (likely negligible g) is: What protection can be expected from gravitational levels between zero-g and one-g? Will crewmembers deconditioned by six months of microgravity exposure on their way to Mars experience continued deconditioning on the Martian surface? Or, will the 3/8 g be sufficient to arrest or even reverse these adaptive changes? The implications for countermeasure deployment, habitat accommodations, and mission design warrant further investigation into the physiological responses to hypogravity. It is not possible to fully simulate hypogravity exposure on Earth for other than transient episodes (e.g., parabolic flight). However, it would be possible to do so in low Earth orbit (LEO) using the centrifugal forces produced in a live-aboard centrifuge. As we're not likely to launch a rotating human spacecraft into LEO anytime in the near future, we could take advantage of rodent subjects aboard the ISS if we had a centrifuge that could accommodate the rodent subjects for extended periods (weeks to months) at various hypogravity levels. Experiments aboard such a centrifuge could provide important insight into human exploration questions and simultaneously answer fundamental questions in gravitational physiology.

Paloski, William H.↗

NASA NTRS2019

Combined Qualification Vibration Testing and Fixed Base Modal Testing Utilizing a Fixed Based Correction Method

Vibration testing spaceflight hardware is a vital, but time consuming and expensive endeavor. Traditionally modal tests are performed at the component, subassembly, or system level, preferably free-free with mass loaded interfaces or fixed base on a seismic mass to identify the fundamental structural dynamic (modal) characteristics. Vibration tests are then traditionally performed on single-axis slip tables at qualification levels that envelope the maximum predicted flight environment plus 3 dB and workmanship in order to verify the spaceflight hardware can survive its flight environment. These two tests currently require two significantly different test setups, facilities, and ultimately reconfiguration of the spaceflight hardware. The vision of this research is to show how traditional fixed-base modal testing can be accomplished using vibration qualification testing facilities, which not only streamlines testing and reduces test costs, but also opens up the possibility of performing modal testing to untraditionally high excitation levels that provide for test-correlated finite element models to be more representative of the spaceflight hardware's response in a flight environment. This paper documents the first steps towards this vision, which is the comparison of modal parameters identified from a traditional fixed-based modal test performed on a modal floor and those obtained by utilizing a fixed based correction method with a large single-axis electrodynamic shaker driving a slip table supplemented with additional small portable shakers driving on the slip table and test article. To show robustness of this approach, the test article chosen is a simple linear weldment, whose mass, size, and modal parameters couple well with the dynamics of the shaker/slip table. This paper will show that all dynamics due to the shaker/slip table were successfully removed resulting in true fixed-base modal parameters, including modal damping, being successfully extracted from a traditional style base-shake vibration test setup.

Winkel, James P.↗

NASA NTRS2019

Combined Qualification Vibration Testing and Fixed Base Modal Testing Utilizing a Fixed Based Correction Method

Vibration testing spaceflight hardware is a vital, but time consuming and expensive endeavor. Traditionally modal tests are performed at the component, subassembly, or system level, preferably free-free with mass loaded interfaces or fixed base on a seismic mass to identify the fundamental structural dynamic (modal) characteristics. Vibration tests are then traditionally performed on single-axis slip tables at qualification levels that envelope the maximum predicted flight environment and workmanship in order to verify the spaceflight hardware can survive its flight environment. These two tests currently require two significantly different test setups, facilities, and ultimately reconfiguration of the spaceflight hardware. The vision of this research is to show how traditional fixed-base modal testing can be accomplished using vibration qualification testing facilities, which not only streamlines testing and reduces test costs, but also opens up the possibility of performing modal testing to untraditionally high excitation levels that provide for test-correlated finite element models to be more representative of the spaceflight hardware's response in a flight environment. This paper documents the first steps towards this vision, which is the comparison of modal parameters identified from a traditional fixed-based modal test performed on a modal floor and those obtained by utilizing a fixed based correction method with a large single-axis electrodynamic shaker driving a slip table supplemented with additional small portable shakers driving on the slip table and test article. To show robustness of this approach, the test article chosen is a simple linear weldment, whose mass, size, and modal parameters couple well with the dynamics of the shaker/slip table. This paper will show that all dynamics due to the shaker/slip table were successfully removed resulting in true fixed-base modal parameters, including modal damping, being successfully extracted from a traditional style base-shake vibration test setup.

Base-Shake↗

NASA NTRS2020

Thoracic Pressure Does Not Impact CSF Pressure via Compartment Compliance

Space acquired neuro-ocular syndrome (SANS) remains a difficult risk to characterize due to the complex multi-factorial etiology related to physiological responses to the spaceflight environment. Fluid shift and the resultant change on the Cardiovascular (CV) and cerebral spinal fluid systems (CSF) in the absence of gravity continue to be considered a contributing factor to the progression of SANS. In this study, we utilize a computational model of the CSF and CV interface to establish the sensitivity that intracranial pressure, and subsequently the optic nerve sheath pressure, exhibits due to variations in thoracic pressure, assuming the cranial perfusion pressure, i.e. mean arterial pressure (MAP) to central venous pressure (CVP), is known. Methods: The GRC Cross cutting computational modeling project created as model of the CSF and CV interaction within the cranial vault by extending the work of Stevens et al. [1] by modifying the representative anatomy to include a separate venous sinus, jugular veins, secondary veins and extra jugular pathways [2-3] to more adequately represent the vascular drainage pathways from the cranial vault (Figure 1). Assuming the MAP, CVP and thoracic pressure are known, we initiated this enhanced computational model assuming a supine positon and utilized a linear ramp to vary the thoracic pressure from the assumed supine state to the target pressure corresponding to set MAP and CVP values. The model generates the time based CSF pressure values (Figure2). Results and Conclusions: Following this analysis, CSF pressure shows significant independence from thoracic pressure changes (16 mmHg in thoracic pressure produces < 1mmHg change in CSF pressure), being mostly dependent on perfusion pressure. Similarly fluid redistribution is not predicted to be impacted over a level of 1mL. We note that this simulation represents an acute changes (order of 10's of minutes) and does not represent the long term effects.

Munster, Drayton W.↗

NASA NTRSDate not supplied

Mitochondria Dysfunction Central in Driving Health Risks Associated with Spaceflight

Background: Determining the biological impact of spaceflight through novel approaches is essential to reduce the health risks to astronauts for long-term space missions. The current established health risks due to spaceflight are only reflecting known symptomatic and physiologic responses and do not reflect early onset of other potential diseases. There are many unknown variables which still need to be identified to fully understand the health impacts due to the environmental factors in space. Materials and Methods: One method to uncover potential novel biological mechanisms responsible for health risks in astronauts is by utilizing NASA’s GeneLab platform (genelab.nasa.gov). GeneLab is public repository that hosts multiple omics datasets generated from space biology experiments that include experiments flown in space, simulated cosmic radiation experiments, and simulated microgravity experiments. This presentation will provide an example of analysis and novel hypothesis generation that is being produced with GeneLab datasets. A comprehensive multi-omics approach was implemented correlating transcriptomics, proteomics, metabolomics, and methylation analysis. Results: We found that cells have stronger overall biological response than the tissues to spaceflight, with mitochondrial activity and innate immunity pathways being heavily impacted. NASA Twin Study results are consistent with a specific alteration in mitochondrial ATP production. Our results indicate that the space environment can directly induce mitochondrial damage, with mitochondrial dysfunctions being a cause for chronic inflammation and both being involved in the development of metabolic disorders that cause changes in lipid metabolism. We also found biological changes occurring during spaceflight with cell cycle, circadian rhythm and olfactory activity pathways can also influence and be influenced by alterations on mitochondrial activity

Afshin Beheshti↗

NASA NTRS2017

So You Want to Go to Mars: Bones and Matters of the Heart

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Collectively, our research team aims to understand the molecular mechanisms underlying the responses of mammalian tissue to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent tissue decrements induced by spaceflight and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will provide an overview of skeletal and cardiovascular responses to spaceflight and will highlight our research progress on understanding the role of reactive oxygen species (ROS) signaling in skeletal responses to radiation and simulated weightlessness.

heart↗

NASA NTRSDate not supplied

Oxidative Stress and Neuroconsequences of the Spaceflight Environment –A 5-ion GCRsim Dose-response Study

The overall scope of this project is to test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we exposed mature (23-24-week-old) male and female mice to simulated 5-Ion GCR (either 0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL). Across ‘Acute’ (IR+72hrs and IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) phases of the 6-month-long study, we assessed immune, neural, and functional (sensorimotor/behavioral/cognitive) responses anticipated during a transit to Mars. This presentation will report on dose-response curves for 5-ion GCRsim related to potential biomarkers; structural/functional changes in the immune and nervous systems; and behavioral/cognitive performance deficits. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.

deep space↗

NASA NTRS1999

T cell activation responses are differentially regulated during clinorotation and in spaceflight

Studies of T lymphocyte activation with mitogenic lectins during spaceflight have shown a dramatic inhibition of activation as measured by DNA synthesis at 72 h, but the mechanism of this inhibition is unknown. We have investigated the progression of cellular events during the first 24 h of activation using both spaceflight microgravity culture and a ground-based model system that relies on the low shear culture environment of a rotating clinostat (clinorotation). Stimulation of human peripheral blood mononuclear cells (PBMCs) with soluble anti-CD3 (Leu4) in clinorotation and in microgravity culture shows a dramatic reduction in surface expression of the receptor for IL-2 (CD25) and CD69. An absence of bulk RNA synthesis in clinorotation indicates that stimulation with soluble Leu4 does not induce transition of T cells from G0 to the G1 stage of the cell cycle. However, internalization of the TCR by T cells and normal levels of IL-1 synthesis by monocytes indicate that intercellular interactions that are required for activation occur during clinorotation. Complementation of TCR-mediated signaling by phorbol ester restores the ability of PBMCs to express CD25 in clinorotation, indicating that a PKC-associated pathway may be compromised under these conditions. Bypassing the TCR by direct activation of intracellular pathways with a combination of phorbol ester and calcium ionophore in clinorotation resulted in full expression of CD25; however, only partial expression of CD25 occurred in microgravity culture. Though stimulation of purified T cells with Bead-Leu4 in microgravity culture resulted in the engagement and internalization of the TCR, the cells still failed to express CD25. When T cells were stimulated with Bead-Leu4 in microgravity culture, they were able to partially express CD69, a receptor that is constitutively stored in intracellular pools and can be expressed in the absence of new gene expression. Our results suggest that the inhibition of T cell proliferative response in microgravity culture is a result of alterations in signaling events within the first few hours of activation, which are required for the expression of important regulatory molecules.

NASA Experiment Number 9403079 1/2↗

NASA NTRS2001

Post-Spaceflight Orthostatic Hypotension Occurs Mostly in Women and is Predicted by Low Vascular Resistance

About 20% of astronauts suffer post-spaceflight presyncope, but the underlying etiology remains elusive. We studied responses to standing in 36 astronauts before and after spaceflight (5- 16 days). Individuals were separated into presyncopal women, presyncopal men, and non-presyncopal men based on their ability to stand for 10 min postflight. Preflight, presyncopal women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced significantly higher rates of presyncope (P<0.01) and significantly greater losses of plasma volume than the men (P<0.05). Both presyncopal women and men had lower standing arterial pressure (P<=0.001) and vascular resistance (P<0.05), smaller increases in norepinephrine (P<=0.058) and greater increases in epinephrine (P<=0.058) than nonpresyncopal men. Both presyncopal groups had a strong dependence (P<=0.05) on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is ascribed to a combination of inherently low resistance responses, a strong dependence on volume status, and spaceflight-induced hypoadrenergic responses. In contrast, high vascular resistance and spaceflight-induced hyperadrenergic responses prevent presyncope.

Waters, Wendy W.↗

NASA NTRS2020

Circulating Mirna Spaceflight Signature Reveals Targets to Mitigate Associated Health Risks

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration, and long-duration spaceflight and regulates vascular damage caused by simulated deep space radiation. In previous studies, we had identified miRNAs that are predicted to regulate rodent responses to spaceflight in low-Earth orbit. Here we have confirmed the expression of these proposed spaceflight associated miRNAs in rodents reacting to simulated spaceflight conditions (exposure to ionizing radiation combined with simulated microgravity) and in astronaut samples from the NASA Twins Study via direct quantification of miRNAs, miRNA sequencing, and inferring miRNA target levels based on single-cell RNA (scRNA-seq) and single-cell chromatin (scATAC-seq) sequencing data. To demonstrate the physiological relevance of key spaceflight associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep space radiation-mediated damage in human 3D vascular constructs.

Sherina Malkani↗

NASA NTRS1997

Mechanisms of Orthostatic Intolerance During Real and Simulated Microgravity

Session MP1 includes short reports on: (1) Orthostatic Tests after 42 Days of Simulated Weightlessness; (2) Effects of 12 Days Exposure to Simulated Microgravity on Central Circulatory Hemodynamics in the Rhesus Monkey; (3) Increased Sensitivity and Resetting of Baroflex Control of Exercise Heart Rate After Prolonged Bed-Rest; (4) Complex Cardiovascular Dynamics and Deconditioning During Head-down Bed Rest; (5) The Cardiovascular Effects of 6 Hours of Head-down Tilt Upon Athletes and Non-athletes; (6) Individual Susceptibility to Post-spaceflight Orthostatic Intolerance: Contributions of Gender-related and Microgravity-related Factors; (7) Cassiopee Mission 1996: Comparison of Cardiovascular Alteration after Short and Long-term Spaceflights; (8) Cerebral and Femoral Flow Response to LBNP during 6 Month MIR Spaceflights (93-95); and (9) Cerebrovascular Changes due to Spaceflight and Postflight Presyncope.

Source record↗

NASA NTRS2020

The NASA Twins Study: The Effect of One Year in Space on Long-Chain Fatty Acid Desaturases and Elongases

Background: To date, there is no clear understanding of the effect of long-duration spaceflight on the major enzymes that govern the metabolism of omega-6 and omega-3 fatty acids. To address this gap in knowledge, we used data from the NASA Twins Study, which includes a multi-scale omic investigation of the changes that occurred during a year-long (340 days) human spaceflight. Embedded within the NASA Twins data are specific analytes associated with fatty acid metabolism. Objectives: To examine the long-chain fatty acid desaturases and elongases in a single human during one year in space. Method: One male twin was on board the International Space Station (ISS) for one year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epigenome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as six months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2 and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions. Results: Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2>0.6) over time for the CD8, CD19, and LD cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the poly-adenylated fraction (polyA) of processed RNAs vs. the ribo-depleted (ribo-) fraction. The flight subject showed a stronger enrichment of the Fatty Acid Metabolic processes pathway across almost all cell types (columns, CD4, CD8, CPT, LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. GSEA enrichment measures across three related Fatty Acid Metabolism pathways showed a differential between the ground and flight subject. Conclusions: There appears to be no persistent alteration of desaturase and elongase gene expression associated with one year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type- and context-specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.

Elongase↗

NASA NTRS1995

Functional and cellular adaptation to weightlessness in primates

Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rate in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to the following: (1) a species difference; (2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or 'free-floating'); and/or (3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

Bodine-Fowler, Sue C.↗

NASA NTRS2015

GeneLab: A Systems Biology Platform for Spaceflight Omics Data

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. Resources to support large numbers of spaceflight investigations are limited. NASA's GeneLab project is maximizing the science output from these experiments by: (1) developing a unique public bioinformatics database that includes space bioscience relevant "omics" data (genomics, transcriptomics, proteomics, and metabolomics) and experimental metadata; (2) partnering with NASA-funded flight experiments through bio-sample sharing or sample augmentation to expedite omics data input to the GeneLab database; and (3) developing community-driven reference flight experiments. The first database, GeneLab Data System Version 1.0, went online in April 2015. V1.0 contains numerous flight datasets and has search and download capabilities. Version 2.0 will be released in 2016 and will link to analytic tools. In 2015 Genelab partnered with two Biological Research in Canisters experiments (BBRIC-19 and BRIC-20) which examine responses of Arabidopsis thaliana to spaceflight. GeneLab also partnered with Rodent Research-1 (RR1), the maiden flight to test the newly developed rodent habitat. GeneLab developed protocols for maxiumum yield of RNA, DNA and protein from precious RR-1 tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected. GeneLab is establishing partnerships with at least three planned flights for 2016. Organism-specific nationwide Science Definition Teams (SDTs) will define future GeneLab dedicated missions and ensure the broader scientific impact of the GeneLab missions. GeneLab ensures prompt release and open access to all high-throughput omics data from spaceflight and ground-based simulations of microgravity and radiation. Overall, GeneLab will facilitate the generation and query of parallel multi-omics data, and deep curation of metadata for integrative analysis, allowing researchers to uncover cellular networks as observed in systems biology platforms. Consequently, the scientific community will have access to a more complete picture of functional and regulatory networks responsive to the spaceflight environment.. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and enable emerging terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space. As a result, open access to the data will foster new hypothesis-driven research for future spaceflight studies spanning basic science to translational science.

proteomics↗

NASA NTRS2001

Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight

Previous investigators have suggested that maximal exercise performed 24 h before the end of bed rest, a spaceflight analog, restores prebed rest plasma volume, baroreflex responses, and orthostatic tolerance. PURPOSE: In this case report, we examined the effect of a similar exercise protocol 24 h before a Shuttle landing on the orthostatic responses of four crewmembers (EX) after spaceflights of 8-14 d. Four additional crewmembers (CON) served as controls and did not perform exercise during the final day of the flight. METHODS: Each crewmember performed a 10-min stand test approximately 10 d before launch (L-10) and within 1-2 h of landing (R+0). Cardiac stroke volume was measured (Doppler ultrasound) supine and during each min of standing for three EX and three CON subjects. RESULTS: Preflight, all crewmembers completed the stand test and each group had similar heart rate and blood pressure responses. Postflight, all subjects also completed the 10-min stand test. Each group had similarly elevated supine and standing heart rates, elevated diastolic and mean arterial blood pressures, and reduced pulse pressures compared to L-10. However, postflight cardiac output, mean +/- SEM, (EX: 4.5+/-0.6 L x min(-1); CON: 3.1+/-0.3 L x min(-1)) and stroke volume (EX: 43+/-7 mL x beat; CON: 30+/-6 mL x beat) were higher after 10 min standing in the EX subjects compared to CON subjects. CONCLUSIONS: For these four crewmembers, maximal exercise performed 24 h before landing may have helped maintain stroke volume but did not maintain heart rate and blood pressure responses during standing compared to preflight.

Flight Experiment↗

NASA NTRS2006

Fault Management Techniques in Human Spaceflight Operations

This paper discusses human spaceflight fault management operations. Fault detection and response capabilities available in current US human spaceflight programs Space Shuttle and International Space Station are described while emphasizing system design impacts on operational techniques and constraints. Preflight and inflight processes along with products used to anticipate, mitigate and respond to failures are introduced. Examples of operational products used to support failure responses are presented. Possible improvements in the state of the art, as well as prioritization and success criteria for their implementation are proposed. This paper describes how the architecture of a command and control system impacts operations in areas such as the required fault response times, automated vs. manual fault responses, use of workarounds, etc. The architecture includes the use of redundancy at the system and software function level, software capabilities, use of intelligent or autonomous systems, number and severity of software defects, etc. This in turn drives which Caution and Warning (C&W) events should be annunciated, C&W event classification, operator display designs, crew training, flight control team training, and procedure development. Other factors impacting operations are the complexity of a system, skills needed to understand and operate a system, and the use of commonality vs. optimized solutions for software and responses. Fault detection, annunciation, safing responses, and recovery capabilities are explored using real examples to uncover underlying philosophies and constraints. These factors directly impact operations in that the crew and flight control team need to understand what happened, why it happened, what the system is doing, and what, if any, corrective actions they need to perform. If a fault results in multiple C&W events, or if several faults occur simultaneously, the root cause(s) of the fault(s), as well as their vehicle-wide impacts, must be determined in order to maintain situational awareness. This allows both automated and manual recovery operations to focus on the real cause of the fault(s). An appropriate balance must be struck between correcting the root cause failure and addressing the impacts of that fault on other vehicle components. Lastly, this paper presents a strategy for using lessons learned to improve the software, displays, and procedures in addition to determining what is a candidate for automation. Enabling technologies and techniques are identified to promote system evolution from one that requires manual fault responses to one that uses automation and autonomy where they are most effective. These considerations include the value in correcting software defects in a timely manner, automation of repetitive tasks, making time critical responses autonomous, etc. The paper recommends the appropriate use of intelligent systems to determine the root causes of faults and correctly identify separate unrelated faults.

O'Hagan, Brian↗

NASA NTRSDate not supplied

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Many microbial pathogens have repeatedly exhibited unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, host-pathogen interactions, and virulence. Notably, the classic foodborne pathogen Salmonella enterica serovar Typhimurium displayed increased virulence in animals when cultured in either the spaceflight analogue or true spaceflight environment. Recently, Serratia marcescens also was shown to increase virulence when cultured in the spaceflight environment. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system at multiple levels, which suggests an increased risk of infectious diseases. Moreover, astronauts have some degree of clinical infectious disease incidence. However, the contribution of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. The goal of this study is to gain insight into the breadth of other medically significant microbial pathogens that may exhibit altered virulence and pathogenesis-related responses when cultured in spaceflight analogue conditions. Specifically, we are characterizing the effect of spaceflight analogue culture (Low Shear Modeled Microgravity/LSMMG) on microbial pathogenesis-related stress responses, in vitro host-pathogen interactions, gene expression, and virulence potential in animals using five important model bacterial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. The information to date is providing a better understanding into the potential impact of microgravity on alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C M Ott↗