Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

Gravitational Force-Induced 3D Chromosomal Conformational Changes Are Associated with Rapid Transcriptional Response in Human T Cells.

The mechanisms underlying gravity perception in mammalian cells are unknown. We have recently discovered that the transcriptome of cells in the immune system, which is the most affected system during a spaceflight, responds rapidly and broadly to altered gravity. To pinpoint potential underlying mechanisms, we compared gene expression and three-dimensional (3D) chromosomal conformational changes in human Jurkat T cells during the short-term gravitational changes in parabolic flight and suborbital ballistic rocket flight experiments. We found that differential gene expression in gravity-responsive chromosomal regions, but not differentially regulated single genes, are highly conserved between different real altered gravity comparisons. These coupled gene expression effects in chromosomal regions could be explained by underlying chromatin structures. Based on a high-throughput chromatin conformation capture (Hi-C) analysis in altered gravity, we found that small chromosomes (chr16-22, with the exception of chr18) showed increased intra- and interchromosomal interactions in altered gravity, whereby large chromosomes showed decreased interactions. Finally, we detected a nonrandom overlap between Hi-C-identified chromosomal interacting regions and gravity-responsive chromosomal regions (GRCRs). We therefore demonstrate the first evidence that gravitational force-induced 3D chromosomal conformational changes are associated with rapid transcriptional response in human T cells. We propose a general model of cellular sensitivity to gravitational forces, where gravitational forces acting on the cellular membrane are rapidly and mechanically transduced through the cytoskeleton into the nucleus, moving chromosome territories to new conformation states and their genes into more expressive or repressive environments, finally resulting in region-specific differential gene expression.

Sixty days of head-down tilt bed rest with or without artificial gravity do not affect the neuromuscular secretome.

Artificial gravity is a potential countermeasure to attenuate effects of weightlessness during long-term spaceflight, including losses of muscle mass and function, possibly to some extent attributable to disturbed neuromuscular interaction. The 60-day AGBRESA bed-rest study was conducted with 24 participants (16 men, 8 women; 33 ± 9 years; 175 ± 9 cm; 74 ± 10 kg; 8 control group, 8 continuous (cAG) and 8 intermittent (iAG) centrifugation) to assess the impact of bed rest with or without daily 30-min continuous/intermittent centrifugation with 1G at the centre of mass. Fasting blood samples were collected before and on day 6, 20, 40 and 57 during 6° head-down tilt bed rest. Concentrations of circulating markers of muscle wasting (GDF-8/myostatin; slow skeletal muscle troponin T; prostaglandin E2), neurotrophic factors (BDNF; GDNF) and C-terminal Agrin Fragment (CAF) were determined by ELISAs. Creatine kinase activity was assessed by colorimetric enzyme assay. Repeated-measures ANOVAs were conducted with TIME as within-subject, and INTERVENTION and SEX as between-subject factors. The analyses revealed no significant effect of bed rest or sex on any of the parameters. Continuous or intermittent artificial gravity is a safe intervention that does not have a negative impact of the neuromuscular secretome.

Tolerability of daily intermittent or continuous short-arm centrifugation during 60-day 6o head down bed rest (AGBRESA study).

Artificial gravity through short-arm centrifugation has potential as a multi-system countermeasure for deconditioning and cranial fluid shifts that may underlie ocular issues in microgravity. However, the optimal short-arm centrifugation protocol that is effective whilst remaining tolerable has yet to be determined. Given that exposure to centrifugation is associated with presyncope and syncope and in addition motion sickness an intermittent protocol has been suggested to be more tolerable. Therefore, we assessed cardiovascular loading and subjective tolerability of daily short arm centrifugation with either an intermittent or a continuous protocol during long-term head-down bed rest as model for microgravity exposure in a mixed sex cohort. During the Artificial Gravity Bed Rest with European Space Agency (AGBRESA) 60 day 6° head down tilt bed rest study we compared the tolerability of daily +1 Gz exposure at the center of mass centrifugation, either performed continuously for 30 minutes, or intermittedly (6 x 5 minutes). Heart rate and blood pressure were assessed daily during centrifugation along with post motion sickness scoring and rate of perceived exertion. During bed rest, 16 subjects (6 women, 10 men), underwent 960 centrifuge runs in total. Ten centrifuge runs had to be terminated prematurely, 8 continuous runs and 2 intermittent runs, mostly due to pre-syncopal symptoms and not motion sickness. All subjects were, however, able to resume centrifuge training on subsequent days. We conclude that both continuous and intermittent short-arm centrifugation protocols providing artificial gravity equivalent to +1 Gz at the center of mass is tolerable in terms of cardiovascular loading and motion sickness during long-term head down tilt bed rest. However, intermittent centrifugation appears marginally better tolerated, albeit differences appear minor.

Motion sickness symptoms during jumping exercise on a short-arm centrifuge.

Artificial gravity elicited through short-arm human centrifugation combined with physical exercise, such as jumping, is promising in maintaining health and performance during space travel. However, motion sickness symptoms could limit the tolerability of the approach. Therefore, we determined the feasibility and tolerability, particularly occurrence of motion sickness symptoms, during reactive jumping exercises on a short-arm centrifuge. In 15 healthy men, we assessed motion sickness induced by jumping exercises during short-arm centrifugation at constant +1Gz or randomized variable +0.5, +0.75, +1, +1.25 and +1.5 Gz along the body axis referenced to center of mass. Jumping in the upright position served as control intervention. Test sessions were conducted on separate days in a randomized and cross-over fashion. All participants tolerated jumping exercises against terrestrial gravity and on the short-arm centrifuge during 1 Gz or variable Gz at the center of mass without disabling motion sickness symptoms. While head movements markedly differed, motion sickness scores were only modestly increased with jumping on the short-arm centrifuge compared with vertical jumps. Our study demonstrates that repetitive jumping exercises are feasible and tolerable during short-arm centrifugation. Since jumping exercises maintain muscle and bone mass, our study enables further development of exercise countermeasures in artificial gravity.

Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation.

Cellular processes are influenced in many ways by changes in gravitational force. In previous studies, we were able to demonstrate, in various cellular systems and research platforms that reactions and adaptation processes occur very rapidly after the onset of altered gravity. In this study we systematically compared differentially expressed gene transcript clusters (TCs) in human Jurkat T cells in microgravity provided by a suborbital ballistic rocket with vector-averaged gravity (vag) provided by a 2D clinostat. Additionally, we included 9× g centrifuge experiments and rigorous controls for excluding other factors of influence than gravity. We found that 11 TCs were significantly altered in 5 min of flight-induced and vector-averaged gravity. Among the annotated clusters were G3BP1, KPNB1, NUDT3, SFT2D2, and POMK. Our results revealed that less than 1% of all examined TCs show the same response in vag and flight-induced microgravity, while 38% of differentially regulated TCs identified during the hypergravity phase of the suborbital ballistic rocket flight could be verified with a 9× g ground centrifuge. In the 2D clinostat system, doing one full rotation per second, vector effects of the gravitational force are only nullified if the sensing mechanism requires 1 s or longer. Due to the fact that vag with an integration period of 1 s was not able to reproduce the results obtained in flight-induced microgravity, we conclude that the initial trigger of gene expression response to microgravity requires less than 1 s reaction time. Additionally, we discovered extensive gene expression differences caused by simple handling of the cell suspension in control experiments, which underlines the need for rigorous standardization regarding mechanical forces during cell culture experiments in general.

A standardized, incremental protocol to increase human tolerance to the cross-coupled illusion.

BACKGROUND: Humans can adapt to the "Coriolis" cross-coupled illusion with repeated exposure, improving the tolerability of faster spin rates and enabling short-radius, intermittent centrifugation for artificial gravity implementation. OBJECTIVE: This investigation assesses the criticality of personalization in acclimation to the cross-coupled illusion. METHODS: We used the median stimulus sequence of our previous effective and tolerable personalized, threshold-based protocol to develop a standardized (non-personalized) approach. During each of 10, 25-minute sessions, the spin rate was incremented independent of whether each subject reported experiencing the cross-coupled illusion. RESULTS: In comparison to the previous personalized protocol, the standardized protocol resulted in significantly reduced acclimation to the cross-coupled illusion (17.7 RPM threshold for the personalized protocol versus 11.8 RPM threshold for the standardized) and generally increased motion sickness reports (average reporting of 1.08/20 (personalized) versus 1.98/20 (standardized)), on average. However, the lack of individualization also leads to significantly less variance in subjects' acclimation. CONCLUSIONS: These findings are critical for future missions that may require several astronauts to be acclimated concurrently, due to resource and time constraints. Assessing feasibility of fast spin rate, short-radius centrifugation is crucial for the future of artificial gravity implementation during spaceflight.

Autophagy protects HUVECs against ER stress-mediated apoptosis under simulated microgravity.

Astronauts exposed to a gravity-free environment experience cardiovascular deconditioning that causes post-spaceflight orthostatic intolerance and other pathological conditions. Endothelial dysfunction is an important factor responsible for this alteration. Our previous study showed enhanced autophagy in endothelial cells under simulated microgravity. The present study explored the cytoprotective role of autophagy under microgravity in human umbilical vein endothelial cells (HUVECs). We found that clinorotation for 48 h induced apoptosis and endoplasmic reticulum (ER) stress in HUVECs. ER stress and the unfolded protein response (UPR) partially contributed to apoptosis under clinorotation. Autophagy partially reduced ER stress and restored UPR signaling by autophagic clearance of ubiquitin-protein aggregates, thereby reducing apoptosis. In addition, the ER stress antagonist 4-phenylbutyric acid upregulated autophagy in HUVECs. Taken together, these findings indicate that autophagy plays a protective role against apoptosis under clinorotation by clearing protein aggregates and partially restoring the UPR.

Tolerable acclimation to the cross-coupled illusion through a 10-day, incremental, personalized protocol.

BACKGROUNDArtificial gravity (AG) has the potential to provide a comprehensive countermeasure mitigating deleterious effects of microgravity. However, the cross-coupled "Coriolis" illusion has prevented using a more feasible and less costly short-radius centrifuge, as compared to large, slowly spinning systems.OBJECTIVEWe assessed tolerability of a personalized, incremental protocol to acclimate humans to the cross-coupled illusion, enabling faster spin rates.METHODSTen subjects were exposed to the illusion by performing roll head tilts while seated upright and spun about an Earth-vertical axis. The spin rate was incremented when head tilts did not subjectively elicit the illusion. Subjects completed one 25-minute session on each of 10 days.RESULTSThe spin rate at which subjects felt no cross-coupled illusion increased in all subjects from an average of 1.8 rotations per minute (RPM) (SD: ±0.9) at the beginning of the protocol to 17.7 RPM (SD: ±9.1) at the end. For off-axis centrifugation producing 1G at the rider's feet, this corresponds to a reduction in the required centrifuge diameter from 552.2 to 5.7 meters. Subjects reported no more than slight motion sickness.CONCLUSIONSAcclimation to the cross-coupled illusion, such as that accomplished here, is critical for feasibility of short-radius centrifugation for AG implementation.

Effects of acute altered gravity during parabolic flight and/or vestibular loss on cell proliferation in the rat dentate gyrus.

Both parabolic flight, i.e. a condition of altered gravity, and loss of vestibular function, have been suggested to affect spatial learning and memory, which is known to be influenced by neurogenesis in the hippocampus. In this study we investigated whether short alternated micro- and hyper-gravity stimulations during parabolic flight and/or loss of vestibular function, would alter cell proliferation in the hippocampal dentate gyrus of rats, by measuring the number of bromodeoxyuridine (BrdU)-incorporated cells. Rats were randomly allocated to the following experimental groups: (1) sham transtympanic saline injection only (n=5); (2) bilateral vestibular deafferentation (BVD) by sodium arsanilate transtympanic injection only (n=5); (3) sham treatment and parabolic flight (n=5); (4) BVD and parabolic flight (n=6). Forty-two days following transtympanic injection, the animals were subjected to parabolic flight in an awake restrained condition after habituation. A modified Airbus A300 aircraft was flown on a parabolic path, creating 20s of 1.8G during both climbing and descending and 22s of 0G at the apex of each parabola. The no flight animals were subjected to the same housing for the same duration. Immediately after the parabolic flight or control ground condition, animals were injected with BrdU (300mg/kg, i.p). Twenty-four hs after BrdU injection, rats were sacrificed. BrdU immunolabelling was performed and the number of BrdU+ve cells in the dentate gyrus of the hippocampus was quantified using a modified fractionator method. BVD caused a large and significant reduction in the number of BrdU-positive cells compared to sham animals (P≤0.0001); however, flight and all interactions were non-significant. These results indicate that BVD significantly decreased cell proliferation irrespective of the short exposure to altered/modified gravity.

Erythrocyte deformability and aggregation responses to intermittent and continuous artificial gravity exposure.

Artificial gravity protocols are used to improve g-tolerance of aviators and discussed as countermeasure during prolonged space flight. Little is known about the impact of artificial gravity on the red blood cells (RBC). The purpose of the study was to test how artificial gravity affects RBC deformability and aggregation, which are important determinants of microcirculation. Nine male subjects were exposed to two hypergravity protocols using a short arm human centrifuge: a continuous (CONT) protocol with constant +2Gz for 30min and an intermittent (INTER) protocol with repeated intervals of +2Gz and rest. Blood was sampled pre and post interventions to measure basal blood parameters, RBC nitrite, RBC deformability, aggregation, and to determine the shear rate balancing aggregation and disaggregation (γ at dIsc min). To test for orthostasis effects, five male subjects were asked to stay for 46min, corresponding to the length of the centrifuge protocols, with blood sampling pre and post intervention. Artificial gravity programs did not affect basal blood parameters or RBC nitrite levels; a marker for RBC deformability influencing nitric oxide. The INTER program did not affect any of the tested parameters. The CONT program did not remarkably affect RBC deformability or γ at dIsc min but significantly aggravated aggregation. Orthostasis effects were thus excluded. The results indicate that continuous artificial gravity, especially with higher g-forces applied, may negatively affect the RBC system and that for a prolonged space flight intermittent but not continuous artificial gravity might represent an appropriate countermeasure.

Impact of a simulated gravity load for atmospheric reentry, 10 g for 2 min, on conscious mice.

The Japan Aerospace Exploration Agency recently performed a mouse experiment in the International Space Station in which mice were raised for 35 days, retrieved using the Dragon spacecraft, and then harvested for analysis 2 days after splashdown. However, the impact of the retrieval procedure, which exposed mice to 5-10 g for 2 min during atmospheric reentry and splashdown, was unknown. Therefore, the purpose of this study was to examine the impact of a 10 g load for 2 min (using a gondola-type centrifuge with a 1.5-m arm installed at Gifu University) on conscious mice. Plasma corticosterone increased at 30 min after load application and recovered at 90 min. Significant Fos expression was observed in the vestibular nuclei (VeN), paraventricular hypothalamic nucleus (PVN), and central nucleus of the amygdala (CeA). Rearing behavior and food intake were suppressed. Mice with vestibular lesions demonstrated increased corticosterone and Fos expression in the PVN, but neither suppression of food intake and rearing behavior nor increased Fos expression in the VeN and CeA. These results suggest that the simulated gravity load induced a transient stress response, hypoactivity, and a vestibular-mediated suppression of food intake.

[MORPHOLOGICAL ASPECTS OF CHANGES IN THE SPINAL GRAY MATTER DUE TO G-LOADS IN EXPERIMENT].

To study changes in spinal cord structures brought about by g-loads, laboratory animals (rats) were rotated on a centrifuge following a special procedure. Systematic g-loads along the craniocaudal axis resulted in reactive alterations, and also obvious destructive processes in the spinal gray matter (SGM). Light optical microscopy discovered that part of neurons had bodies with less intensive dying. Electron microscopy showed that among the cytoplasmic structures mitochondria were particularly sensitive to g-loads, which could affect mitochondrial oxidation. In the lumbar, these changes were observed in every segment under study; they were more significant in comparison with those found in cervical and thoracic segments of the spinal cord. Interneuron disintegration at neural centers revealed itself by the "light" type degeneration of synapses. Changes in capillaries included nuclei deformations and destruction of organelles in endotheliocytes, pericapillary edema, and erythrocytes sludge in the lumen. Inequality of spinal cord changes suggests the mosaic pattern of their distribution. Furthermore, their manifestation grew with the cranicaudal gradient so that the most conspicuous destructive developments occurred in the lumbar but not in the thoracic let alone the cervical segment. Acute g-loads gave rise to reactive changes in neurons and interneuron synapses that were the morphological markers of increased functional activity of neurons and activation of interneuron firing. In addition to the reactive changes, chronic g-loading also produced destructive disorders in GSM structures. These changes were not observed following acute g-loads and, therefore, resulted from multiple g-exposures and were cumulative.

Effects of individualized centrifugation training on orthostatic tolerance in men and women.

AIMS: Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known. METHODS: We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure (90 minutes) in supine position [protocol 1, artificial gravity exposure], or 2) lay supine on the centrifuge for 90 minutes in supine position without AG exposure [protocol 2, control]. The AG training protocol was individualized, by first determining each subject's maximum tolerable G load, and then exposing them to 45 minutes of ramp training at sub-presyncopal levels. RESULTS: Both sexes had improved OTL (14 minutes vs 11 minutes, p < 0.0019) following AG exposure. When cardiovascular (CV) variables at presyncope in the control test were compared with the CV variables at the same tilt-test time (isotime) during post-centrifuge, higher blood pressure, stroke volume and cardiac output and similar heart rates and peripheral resistance were found post-centrifuge. CONCLUSIONS: These data suggest a better-maintained central circulating blood volume post-centrifugation across gender and provide an integrated insight into mechanisms of blood pressure regulation and the possible implementation of in-flight AG countermeasure profiles during spaceflights.

Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

BACKGROUND AND PURPOSE: Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. METHODS: We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. RESULTS: Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. CONCLUSIONS: Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

Space headache on Earth: head-down-tilted bed rest studies simulating outer-space microgravity.

BACKGROUND: Headache is a common symptom during space travel, both isolated and as part of space motion syndrome. Head-down-tilted bed rest (HDTBR) studies are used to simulate outer space microgravity on Earth, and allow countermeasure interventions such as artificial gravity and training protocols, aimed at restoring microgravity-induced physiological changes. OBJECTIVES: The objectives of this article are to assess headache incidence and characteristics during HDTBR, and to evaluate the effects of countermeasures. METHODS: In a randomized cross-over design by the European Space Agency (ESA), 22 healthy male subjects, without primary headache history, underwent three periods of -6-degree HDTBR. In two of these episodes countermeasure protocols were added, with either centrifugation or aerobic exercise training protocols. Headache occurrence and characteristics were daily assessed using a specially designed questionnaire. RESULTS: In total 14/22 (63.6%) subjects reported a headache during ≥1 of the three HDTBR periods, in 12/14 (85.7%) non-specific, and two of 14 (14.4%) migraine. The occurrence of headache did not differ between HDTBR with and without countermeasures: 12/22 (54.5%) subjects vs. eight of 22 (36.4%) subjects; p = 0.20; 13/109 (11.9%) headache days vs. 36/213 (16.9%) headache days; p = 0.24). During countermeasures headaches were, however, more often mild (p = 0.03) and had fewer associated symptoms (p = 0.008). CONCLUSIONS: Simulated microgravity during HDTBR induces headache episodes, mostly on the first day. Countermeasures are useful in reducing headache severity and associated symptoms. Reversible, microgravity-induced cephalic fluid shift may cause headache, also on Earth. HDTBR can be used to study space headache on Earth.

Integrin αvß3 mediates the synergetic regulation of core-binding factor α1 transcriptional activity by gravity and insulin-like growth factor-1 through phosphoinositide 3-kinase signaling.

Mechanical stimulation and biological factors coordinately regulate bone development and regeneration; however, the underlying mechanisms are poorly understood. Microgravity induces bone loss, which may be partly related to the development of resistance to local cytokines, including insulin-like growth factor 1 (IGF-1). Here, we report the involvement of integrin αvß3 in microgravity-associated bone loss. An established OSE-3T3 cell model was stably transfected with a 6OSE2 (Osteoblast-Specific Element 2)-luciferase reporter and cultured under simulated microgravity (SMG) and hypergravity (HG) conditions in the presence or absence of IGF-1, the disintegrin echistatin, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, or combinations of these agents. Activity of core-binding factor α1 (Cbfa1), an essential transcription factor for osteoblastic differentiation and osteogenesis, was reflected by luciferase activity. Different gravity conditions affected the induction of IGF-1 and subsequent effects on Cbfa1 transcription activity. SMG and HG influenced the expression and activity of integrin αvß3 and phosphorylation level of p85. LY294002 inhibited the effects of HG or IGF-1 on Cbfa1 activity, indicating that HG and IGF-1 could increase Cbfa1 activity via PI3K signaling. Inhibition of integrin αvß3 by echistatin attenuated the induction of IGF-1 and thus its effect on Cbfa1 activity under normal and HG conditions. Co-immunoprecipitation demonstrated that integrin ß3 interacted with insulin receptor substrate 1, and that this interaction was decreased under SMG and increased under HG conditions. These results suggest that integrin αvß3 mediates the synergetic regulation of Cbfa1 transcription activity by gravity and IGF-1 via PI3K signaling.

Simulations of gravitational stress on normovolemic and hypovolemic men and women.

BACKGROUND: Earth-based simulations of physiologic responses to space mission activities are needed to develop prospective countermeasures. To determine whether upright lower body positive pressure (LBPP) provides a suitable space mission simulation, we investigated the cardiovascular responses of normovolemic and hypovolemic men and women to supine and orthostatic stress induced by head-up tilt (HUT) and upright LBPP, representing standing in lunar, Martian, and Earth gravities. METHODS: Six men and six women were tested in normovolemic and hypovolemic (furosemide, intravenous, 0.5 mg x kg(-1)) conditions. Continuous electrocardiogram, blood pressure, segmental bioimpedance, and stroke volume (echocardiography) were recorded supine and at lunar, Martian, and Earth gravities (10 degrees, 20 degrees, and 80 degrees HUT vs. 20%, 40%, and 100% bodyweight upright LBPP), respectively. Cardiovascular responses were assessed from mean values, spectral powers, and spontaneous baroreflex parameters. RESULTS: Hypovolemia reduced plasma volume by approximately 10% and stroke volume by approximately 25% at supine, and increasing orthostatic stress resulted in further reductions. Upright LBPP induced more plasma volume losses at simulated lunar and Martian gravities compared with HUT, while both techniques induced comparable central hypovolemia at each stress. Cardiovascular responses to orthostatic stress were comparable between HUT and upright LBPP in both normovolemic and hypovolemic conditions; however, hypovolemic blood pressure was greater during standing at 100% bodyweight compared to 80 degree HUT due to a greater increase of total peripheral resistance. CONCLUSIONS: The comparable cardiovascular response to HUT and upright LBPP support the use of upright LBPP as a potential model to simulate activity in lunar and Martian gravities.

Artificial gravity exposure impairs exercise-related neurophysiological benefits.

Artificial gravity (AG) exposure is suggested to counteract health deconditioning, theoretically complementing exercise during space habitations. Exercise-benefits on mental health are well documented (i.e. well-being, enhanced executive functions). Although AG is coherent for the integrity of fundamental physiological systems, the effects of its exposure on neurophysiological processes related to cognitive performance are poorly understood and therefore characterize the primary aim of this study. 16 healthy males participated in two randomly assigned sessions, AG and exercise (30minute each). Participants were exposed to AG at continuous +2Gz in a short-arm human centrifuge and performed moderate exercise (cycling ergometer). Using 64 active electrodes, resting EEG was recorded before (pre), immediately after (post), and 15min after (post15) each session. Alpha (7.5-12.5Hz) and beta frequencies (12.5-35.0Hz) were exported for analysis. Cognitive performance and mood states were assessed before and after each session. Cognitive performance improved after exercise (p<0.05), but not after AG. This was reflected by typical EEG patterns after exercise, however not after AG. Frontal alpha (post p<0.01, post15 p<0.001) and beta activity (post15 p<0.001) increased after AG compared to a decrease in frontal alpha (post15 p<0.05) and beta activity (post p<0.01) after exercise. Relaxed cortical states were indicated after exercise, but were less apparent after AG. Changes in mood states failed significance after both sessions. Summarized, the benefits to mental health, recorded after exercise, were absent after AG, indicating that AG might cause neurocognitive deconditioning.