Head-down Tilt Bed Rest Research Articles

Internal Jugular Vein Volume During Head-Down Tilt and Carbon Dioxide Exposure in the SPACECOT Study.

Cerebral hemodynamics and venous outflow from the brain may be altered during exposure to microgravity or head-down tilt (HDT), an analog of microgravity, as well as by increased ambient CO2 exposure as experienced on the International Space Station. Six healthy subjects underwent baseline tilt table testing at 0°, 6°, 12°, 18°, 24°, and 30° HDT. The right internal jugular (IJ) vein cross-sectional area (CSA) was measured at four intervals from the submandibular to the clavicular level and IJ volume was calculated. Further measurements of the IJ vein were made after ∼26 h of 12° HDT bed rest with either ambient air or 0.5% CO2 exposure, and plasma and blood volume were assessed after 4 h, 24 h, and 28.5 h HDT. IJ vein CSA and volume increased with progressively steeper HDT angles during baseline tilt table testing, with more prominent filling of the IJ vein at levels closer to the clavicle. Exposure to 26 h of 12° HDT bed rest with or without increased CO2, however, had little additional effect on the IJ vein. Further, bed rest resulted in a decrease in plasma volume and blood volume, although changes did not depend on atmospheric conditioning or correlate directly with changes in IJ vein CSA or volume. The hydrostatic effects of HDT can be clearly determined through measurement of the IJ vein CSA and volume; however, IJ vein dimensions may not be a reliable indicator of systemic fluid status during bed rest.Marshall-Goebel K, Stevens B, Rao CV, Suarez JI, Calvillo E, Arbeille P, Sangi-Haghpeykar H, Donoviel DB, Mulder E, Bershad EM, the SPACECOT Investigators Group. Internal jugular vein volume during head-down tilt and carbon dioxide exposure in the SPACECOT Study. Aerosp Med Hum Perform. 2018; 89(4):351-356.

VaPER: The Development of Spaceflight Associated Neuro‐ocular Syndrome (SANS) During Hypercapnic 6° Head‐Down Tilt Bed Rest; sans Sufficient Sleep?

OBJECTIVETo determine whether the combination of a cephalad fluid shift induced by headdown tilt (HDT) bed rest and chronic exposure to mild hypercapnia for 30 days will alter sleep architecture and circadian rhythm, contributing to characteristics of Spaceflight Associated Neuro‐ocular Syndrome (SANS).METHODSAfter 14 days of ambulatory normocapnic familiarization with the facility and baseline data collection (BDC), eleven subjects (5 female) breathed mild, ambient hypercapnia (0.5% CO2) throughout 30 days of 6° HDT at the German Aerospace Center (DLR): envihab facility. Following HDT, subjects were monitored for an additional 14 days of ambulatory, normocapnic recovery (R). Overnight polysomnography (PSG) was measured using a type‐2 sleep monitoring system, and the PSG was scored by a Polysomnographic Technologist to assess sleep duration, staging, latency, and arousals. Circadian rhythm was assessed by monitoring 24‐hour core body temperature with rectal temperature probes. Arterial PCO2 levels were estimated from transcutaneous PCO2 monitoring throughout sleep. Retinal thickness was measured via optical coherence tomography (OCT); those with increased thickness >50μ in the nasal quadrant were classified as RET+, those <50μ were classified as RET‐. After one night of familiarization with the instrumentation, measurements were collected at six different time points (one BDC, three HDT, and two R).RESULTSWhen comparing RET+ to RET‐, subjects had: significantly less total sleep time (TST) in BDC (345 ± 25 min vs 401 ± 23 min, p < 0.05), HDT4 (303 ± 64 min vs 375 ± 20 min, p < 0.05), HDT28 (344 ± 59 min vs 407 ± 32 min, p < 0.05), and R+4 (344 ± 68 min vs 421 ± 21 min, p < 0.05); significantly less stage 2 (N2) sleep in HDT4 (157 ± 43 min vs 220 ± 9 min, p < 0.05), HDT28 (198 ± 32 min vs 256 ± 21 min, p < 0.05), and R+4 (187 ± 74 min vs 271 ± 32, p < 0.05); significantly more wake after sleep onset (WASO) in HDT4 (147 ± 85 min vs 57 ± 27 min, p < 0.05) and R+4 (134 ± 106 min vs 41 ± 12 min, p < 0.05); and a significantly reduced core body temperature amplitude at BDC (0.3 ± 0.1 deg vs 0.5 ± 0.1 deg, p < 0.05), HDT4 (0.2 ± 0.1 deg vs 0.4 ± 0.1 deg, p < 0.05), HDT28 (0.3 ± 0.1 deg vs 0.4 ± 0.1 deg, p < 0.05), and R+10 (0.3 ± 0.0 deg vs 0.4 ± 0.1 deg, p < 0.05).CONCLUSIONSPrior to and throughout the experimental conditions, when compared to RET‐, RET+ subjects were “short” sleepers and in general had less N2 sleep, greater WASO, and had a lower amplitude of core body temperature. We conclude that insufficient sleep may predispose certain individuals to the development of retinal thickening, a finding of SANS. Objective PSG may be a potential variable to consider when determining astronaut spaceflight duration.Support or Funding InformationNASA Human Research Program NNJ14ZSA001NThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Vestibular brain changes within 70 days of head down bed rest.

Head-down-tilt bed rest (HDBR) is frequently utilized as a spaceflight analog research environment to study the effects of axial body unloading and fluid shifts that are associated with spaceflight in the absence of gravitational modifications. HDBR has been shown to result in balance changes, presumably due to sensory reweighting and adaptation processes. Here, we examined whether HDBR results in changes in the neural correlates of vestibular processing. Thirteen men participated in a 70-day HDBR intervention; we measured balance, functional mobility, and functional brain activity in response to vestibular stimulation at 7 time points before, during, and after HDBR. Vestibular stimulation was administered by means of skull taps, resulting in activation of the vestibular cortex and deactivation of the cerebellar, motor, and somatosensory cortices. Activation in the bilateral insular cortex, part of the vestibular network, gradually increased across the course of HDBR, suggesting an upregulation of vestibular inputs in response to the reduced somatosensory inputs experienced during bed rest. Furthermore, greater increase of activation in multiple frontal, parietal, and occipital regions in response to vestibular stimulation during HDBR was associated with greater decrements in balance and mobility from before to after HDBR, suggesting reduced neural efficiency. These findings shed light on neuroplastic changes occurring with conditions of altered sensory inputs, and reveal the potential for central vestibular-somatosensory convergence and reweighting with bed rest.

Change of cortical foot activation following 70 days of head-down bed rest.

Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to study some of the effects of microgravity on human physiology, cognition, and sensorimotor functions. Previous studies have reported declines in balance control and functional mobility after spaceflight and HDBR. In this study we investigated how the brain activation for foot movement changed with HDBR. Eighteen healthy men participated in the current HDBR study. They were in a 6° head-down tilt position continuously for 70 days. Functional MRI scans were acquired to estimate brain activation for foot movement before, during, and after HDBR. Another 11 healthy men who did not undergo HDBR participated as control subjects and were scanned at four time points. In the HDBR subjects, the cerebellum, fusiform gyrus, hippocampus, and middle occipital gyrus exhibited HDBR-related increases in activation for foot tapping, whereas no HDBR-associated activation decreases were found. For the control subjects, activation for foot tapping decreased across sessions in a couple of cerebellar regions, whereas no activation increase with session was found. Furthermore, we observed that less HDBR-related decline in functional mobility and balance control was associated with greater pre-to-post HDBR increases in brain activation for foot movement in several cerebral and cerebellar regions. Our results suggest that more neural control is needed for foot movement as a result of HDBR. NEW & NOTEWORTHY Long-duration head-down bed rest serves as a spaceflight analog research environment. We show that brain activity in the cerebellum and visual areas during foot movement increases from pre- to post-bed rest and then shows subsequent recovery. Greater increases were seen for individuals who exhibited less decline in functional mobility and balance control, suggestive of adaptive changes in neural control with long-duration bed rest.

Myocellular Responses to Concurrent Flywheel Training during 70 Days of Bed Rest.

This investigation evaluated myocellular responses to an integrated resistance and aerobic training program during 70 d of bed rest. Training was 6 d·wk on a small-footprint gravity-independent flywheel resistance and aerobic device; 3 d of maximal flywheel supine quadriceps and calf exercises with continuous rowing separated by 4 to 6 h, and 3 d of interval rowing. Vastus lateralis (VL) and soleus (SOL) muscle biopsies were obtained from eight healthy males (age, 28 ± 4 yr; BMI, 25 ± 3 kg·m; V˙O2max, 42 ± 6 mL·kg·min) before and after 6° head-down tilt bed rest. Vastus lateralis and SOL myosin heavy chain (MHC) I and IIa single muscle fiber size and functional characteristics, as well as overall fiber type distribution, capillarization, and metabolic enzyme activities were evaluated. In the VL, MHC I size and power (absolute and normalized) were preserved. The MHC IIa fibers hypertrophied (+6%, P < 0.05) without a change in absolute power, so normalized power declined (-7%, P < 0.05). In the SOL, MHC I fibers atrophied (-9%) and absolute power declined (-17%) (P < 0.05), whereas normalized power was maintained. Size, absolute power, and normalized power were protected in the less-abundant MHC IIa fibers. Reduced MHC coexpressing hybrid fibers, generally indicative of an exercise training effect, was apparent in the VL, whereas fiber type was maintained in the SOL. Capillarization and metabolic enzymes were generally preserved or increased in VL and SOL. The integrated resistance and aerobic training protocol on a device maintains several key myocellular characteristics during prolonged unloading, but further refinement of the exercise approach to fully protect the SOL is warranted.

Incretion of Insulin by Pancreas and Its Inactivation in Women during Long-Term Head-down Tilt Bed Rest

An increase in insular activity in response to hyperglycemia when performing a glucose tolerance test (GTT) during normal physical activity in eight women volunteers was found to be associated with increased blood concentrations of insulin provided by an increase in secretion rate and a decrease in inactivation rate. After 81 days of stay in long-term –6° head-down tilt bed rest (bed rest), flattened glycemic curves (with low hyperglycemic lifting) observed during the GTT, what was indicated high insular activity. An increase in the insular activity was evidencing also by a smaller peak of the blood concentration of glucose from 5 min after intravenous nfusion of 20 mL of 40% glucose solution at 120 minute of the GTT. In bed rest on empty stomach no significant changes in the concentrations of insulin and C-peptide were observed. The dynamics of hormone during the GTT was showed that the appearance of flattened glycemic curves when performing GTT during bed rest was associated with more pronounced, than under the usual conditions, an increase in insulin concentration in response to hyperglycemia. An increase in the blood insulin concentration when performing GTT in bed rest was mainly provided by increased hormone secretion rate in the pancreas, but not by a decrease in its inactivation rate. If you use regular exercises for prevention of hypokinesia under conditions of bed rest, an increase in insulin concentration during GTT was mainly provided by a decrease in its inactivation rate and not by an increase in secretion rate.

Effects of -12° head-down tilt with and without elevated levels of CO2 on cognitive performance: the SPACECOT study.

Microgravity and elevated levels of CO2 are two common environmental stressors in spaceflight that may affect cognitive performance of astronauts. In this randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean ± SD age: 41 ± 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2 concentrations during 26.5-h periods of -12° head-down tilt (HDT) bed rest with a 1-wk washout period between exposures. Subjects performed the 10 tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h after the initiation of HDT bed rest. HDT in ambient air induced a change in response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the expense of accuracy (-0.19 SD; P = 0.2867), resulting in comparable cognitive efficiency. The observed effects were small and statistically significant for cognitive speed only. However, even small declines in accuracy can potentially cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient air. This was possibly related to hypercapnia-induced cerebrovascular reactivity that favors cortical regions in general and the frontal cortex in particular, or to the CNS arousing properties of mildly to moderately increased CO2 levels. There were no statistically significant time-in-CO2 effects for any cognitive outcome. The small sample size and the small effect sizes are major limitations of this study and its findings. The results should not be generalized beyond the group of investigated subjects until they are confirmed by adequately powered follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h of -12° head-down tilt bed rest caused a change in response strategy on a range of cognitive tests, with a statistically significant increase in response speed at the expense of accuracy. Cognitive efficiency was not affected. The observed speed-accuracy tradeoff was small but may nevertheless be important for mission-critical tasks in spaceflight. Importantly, the change in response strategy was reversed by increasing CO2 concentrations to 0.5%.

Long-duration bed rest modifies sympathetic neural recruitment strategies in male and female participants.

To understand the impact of physical deconditioning with head-down tilt bed rest (HDBR) on the malleability of sympathetic discharge patterns, we studied 1) baseline integrated muscle sympathetic nerve activity (MSNA; microneurography) from 13 female participants in the WISE-2005 60-day HDBR study (retrospective analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13 male participants performed on data collected at baseline and during physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study, and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk between tests). Neither baseline integrated burst frequency nor incidence were altered with HDBR (both P > 0.35). However, baseline integrated burst latency increased in both HDBR studies (male: 1.35 ± 0.02 to 1.39 ± 0.02 s, P < 0.01; female: 1.23 ± 0.02 to 1.29 ± 0.02 s, P < 0.01), whereas controls exhibited no change across two visits (1.25 ± 0.02 to 1.25 ± 0.02 s, group-by-time interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03), male baseline AP data did not change with HDBR (all P > 0.19). The change in AP frequency on going from baseline to apnea (∆94 ± 25 to ∆317 ± 55 AP/min, P < 0.01) and the number of active sympathetic clusters per burst (∆0 ± 0.2 to ∆1 ± 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The change in total clusters with apnea was ∆0 ± 0.5 clusters pre- and ∆2 ± 0.7 clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified discharge characteristics in baseline burst latency and sympathetic neural recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not modify baseline sympathetic burst frequency in male and female participants, but examination of additional features of the multiunit signal provided novel evidence to suggest augmented synaptic delays or processing times at baseline for all sympathetic action potentials. Furthermore, long-duration bed rest increased reflex-sympathetic arousal to apneic stress in male participants primarily by mechanisms involving an augmented firing rate of action potential clusters active at baseline.

Objects Mental Rotation under 7 Days Simulated Weightlessness Condition: An ERP Study.

During the spaceflight under weightlessness condition, human's brain function may be affected by the changes of physiological effects along with the distribution of blood and body fluids to the head. This variation of brain function will influence the performance of astronauts and therefore create possible harm to flight safety. This study employs 20 male subjects in a 7-day−6° head-down tilted (HDT) bed rest model to simulate physiological effects under weightlessness condition, and use behavioral, electrophysiological techniques to compare the changes of mental rotation ability (MR ability) before and after short-term simulated weightlessness state. Behavioral results suggested that significant linear relationship existed between the rotation angle of stimuli and the reaction time, which means mental rotation process do happen during the MR task in simulated weightlessness state. In the first 3 days, the P300 component induced by object mental rotation followed the “down-up-down” pattern. In the following 4 days it changed randomly. On HDT D2, the mean of the amplitude of the P300 was the lowest, while increased gently on HDT D3. There was no obvious changing pattern of the amplitude of P300 observed after 3 days of HDT. Simulated weightlessness doesn't change the basic process of mental rotation. The effect of simulated weightlessness is neural mechanism of self-adaptation. MR ability didn't bounce back to the original level after HDT test.

Head-down tilt bed-rest significantly increases central arterial stiffness

The vascular system is subject to continual variation in mechanical stresses, both physiological and pathological. Vascular remodeling via changes in vessel wall properties, including thickness and stiffness, is a major feature of aging and cardiovascular disease.A more detailed understanding of the interplay between mechanical stress, aging, CVD and vascular remodeling will aid prevention of increased cardiovascular risk following long term microgravity.This study aims at assessing vascular remodeling processes resulting from a 60-day head-down-tilt bed-rest period during the European Space Agency Study (Toulouse, France).We hypothesize that arterial remodeling processes are modified by long term bed- rest and constitute a significant cardiovascular risk in the long term for astronauts. Applanation tonometry is used to assess carotid to femoral pulse wave velocity (PWV) and non-invasive ultrasound imaging are used to assess arterial remodelling processes at the carotid, femoral, brachial and popliteal arteries.Measurements are performed at baseline; at day 29 and 52 of bed-rest; and at day 6 and 30 of the recovery period.The preliminary results including 10 first subjects, demonstrate a strong effect of bed- rest on arterial PWV.The average PWV at baseline equals 7,6 ± 1.4m/s and is increased to 9.0 ± 1.9m/s after 29 days, and, 9.3 ± 1.8m/s after 52 days bed-rest. This increase is significantly different between baseline, and, 29 and 52 days bed-rest (p < 0.005).Increase in PWV suggests a rapid and significant stiffening of the central arteries, which on healthy subjects corresponds to an aging process wich occurs many years. Low gravity conditions as during bed-rest induce significant arterial stiffening that could be linked to long term CVD risks for either patients in bed-rest or astronauts.

Bed Rest and Intermittent Centrifugation Effects on Human Balance and Neuromotor Reflexes.

The effects of repeated centrifugation in association with head-down tilt (HDT) bed rest (BR) on the mediation of basic reflexes associated with the major postural muscles was investigated as a potential countermeasure for maintaining balance control and neuromotor reflex function. There were 15 male volunteers who were exposed to 21 d of 6° HDT-BR. Eight were treated with daily 1-h artificial gravity (AG) exposures aboard a short radius centrifuge that provided 1-g footward loading at heart level. The other seven served as HDT-BR control subjects. Balance control was assessed using a standard computerized dynamic posturography (CDP) protocol that was modified by adding low-frequency pitch-plane head movements. Neuromotor reflex function was assessed using tendon stretch reflexes (MSR) and functional stretch reflex (FSR) data collected from the triceps surae muscle group. CDP performance was degraded by HDT-BR in both groups (ranging from 24 to 26%), but was unaffected by AG. BR also degraded MSR and FSR functions in both groups, with increased peak reflex latencies between 1.5 and 1.95 ms, but AG maintained pre-BR latencies for the MSR subjects. AG exposure did not modify balance control from pre-BR responses, but did help prevent decrements in FSR latencies post-BR.Paloski WH, Reschke MF, Feiveson AH. Bed rest and intermittent centrifugation effects on human balance and neuromotor reflexes. Aerosp Med Hum Perform. 2017; 88(9):812-818.

Ophthalmological Evaluation of Integrated Resistance and Aerobic Training During 70-Day Bed Rest.

We evaluated ophthalmic changes in healthy individuals who underwent integrated resistance and aerobic training (iRAT) during 70-d 6° head-down tilt (HDT) bed rest (BR). Participants were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects were randomly assigned to the iRAT protocol or no exercise during HDTBR. Weekly ophthalmic examinations were performed in the sitting (pre/post-BR only) and HDT (BR only) positions. Mixed-effects linear models compared pre- and post-HDTBR intraocular pressure (IOP), Spectralis OCT circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and peripapillary retinal thickness observations between groups. Six controls and nine exercisers completed the study. There was an overall effect of BR on our outcomes. Except Goldmann IOP (mean pre/post difference in controls and exercisers: -0.47 mmHg vs. +1.14 mmHg), the magnitude of changes from baseline was not significantly different between groups. There was a +1.38 mmHg and a +1.63 mmHg iCare IOP increase during BR in controls and exercisers, respectively. Spectralis OCT detected a +1.33 μm average cpRNFL thickness increase in both groups, and a +9.77 μm and a +6.65 μm peripapillary retinal thickening post-BR in controls and exercisers, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable. HDTBR for 70 d induced peripapillary retinal thickening and cpRNFL thickening without visible signs of optic disc edema. The magnitude of such changes was not different between controls and exercisers. A slight IOP increase during BR subsided post-BR. Further study should evaluate whether different physical exercise paradigms may prevent/mitigate the risk of space-related visual impairment.Taibbi G, Cromwell RL, Zanello SB, Yarbough PO, Ploutz-Snyder RJ, Godley BF, Vizzeri G. Ophthalmological evaluation of integrated resistance and aerobic training during 70-day bed rest. Aerosp Med Hum Perform. 2017; 88(7):633-640.

Intracranial Fluid Redistribution But No White Matter Microstructural Changes During a Spaceflight Analog

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions.Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA.Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients.

An international collaboration studying the physiological and anatomical cerebral effects of carbon dioxide during head-down tilt bed rest: the SPACECOT study.

Exposure to the microgravity environment results in various adaptive and maladaptive physiological changes in the human body, with notable ophthalmic abnormalities developing during 6-mo missions on the International Space Station (ISS). These findings have led to the hypothesis that the loss of gravity induces a cephalad fluid shift, decreased cerebral venous outflow, and increased intracranial pressure, which may be further exacerbated by increased ambient carbon dioxide (CO2) levels on the ISS. Here we describe the SPACECOT study (studying the physiological and anatomical cerebral effects of CO2 during head-down tilt), a randomized, double-blind crossover design study with two conditions: 29 h of 12° head-down tilt (HDT) with ambient air and 29 h of 12° HDT with 0.5% CO2 The internationally collaborative SPACECOT study utilized an innovative approach to study the effects of headward fluid shifting induced by 12° HDT and increased ambient CO2 as well as their interaction with a focus on cerebral and ocular anatomy and physiology. Here we provide an in-depth overview of this new approach including the subjects, study design, and implementation, as well as the standardization plan for nutritional intake, environmental parameters, and bed rest procedures.NEW & NOTEWORTHY A new approach for investigating the combined effects of cephalad fluid shifting and increased ambient carbon dioxide (CO2) is presented. This may be useful for studying the neuroophthalmic and cerebral effects of spaceflight where cephalad fluid shifts occur in an elevated CO2 environment.

Circulating microRNAs Correlated with Bone Loss Induced by 45 Days of Bed Rest.

The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with bone loss induced by bed rest, and testify whether the selected miRNAs could reflect the bone mineral status of human after bed-rest. We analyzed plasma miRNA levels of 16 subjects after 45 days of −6° head-down tilt bed rest, which is a reliable model for the simulation of microgravity. We characterize the circulating miRNA profile in individuals after bed rest and identify circulating miRNAs which can best reflect the level of bone loss induced by bed rest. Expression profiling of circulating miRNA revealed significant downregulation of 37 miRNAs and upregulation of 2 miRNAs, while only 11 of the downregulated miRNAs were further validated in a larger volunteer cohort using qPCR. We found that 10 of these 11 miRNAs (miR-103, 130a, 1234, 1290, 151-5p, 151-3p, 199a-3p, 20a, 363, and 451a) had ROC curve that distinguished the status after bed rest. Importantly, significant positive correlations were identified between bone loss parameters and several miRNAs, eventually miR-1234 showed clinical significance in detecting the bone loss of individuals after 45 days of bed rest.

Effect of gravity and microgravity on intracranial pressure.

Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90deg seated upright posture on Earth. Thus, over 24h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts. Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission-critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1year. ICP was assessed by placing a fluid-filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6deg head-down tilt bedrest). ICP was lower when seated in the 90deg upright posture compared to lying supine (seated, 4±1 vs. supine, 15±2mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7±3 vs. microgravity, 4±2mmHg) and ICP (supine, 17±2 vs. microgravity, 13±2mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15±2vs. 24h head-down tilt, 15±4mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.

Exercise and Transversus Abdominis Muscle Atrophy after 60-d Bed Rest.

This study aimed to investigate atrophy in the deep abdominal muscles, spinal extensors, and the effect of high-load resistive exercise with and without whole-body vibration after 60 d of strict bed rest. Twenty-four subjects underwent 60 d of head-down tilt bed rest and performed either resistive vibration exercise (RVE), resistive exercise only (RE), or no exercise control (2nd Berlin BedRest Study). The thickness of the transversus abdominis, internal oblique, and erector spinae muscles and the area of the multifidus muscle were measured bilaterally via real-time ultrasound. Intention-to-treat analysis was implemented, and P values were adjusted by the false discovery rate method. At the end of the bed rest, transversus abdominis thickness was reduced by 18.3% in the inactive group (P = 0.00011) with no significant change in the RVE (-4.0%; P = 0.014 vs control) or RE (-5.0%; P = 0.10 vs control) groups. In the inactive subjects, internal oblique thickness reduced by 10.6% (P = 0.0025) and by 7% (P > 0.05) in each of the training groups. The lengthening of the lumbar spine was greatest on day 1 (+7.4%, P = 0.004) and day 2 (+6.3%, P = 0.004; day 54: +4.1%, P = 0.023). A 4.7% reduction of multifidus area was observed on day 1 of bed rest (P = 0.0049) and a 4.2% reduction of erector spinae thickness was observed on day 2 (P = 0.0011). Extensor atrophy and spinal lengthening was not affected by exercise. No significant difference was seen between RVE and RE. Bed rest leads to atrophy of the transversus abdominis and internal oblique muscles. The exercise program, which implemented lower-limb and back extension exercises against shoulder restraints, was able to reduce atrophy seen in transversus abdominis in bed rest.

HEALTHY STATE MONITOR OF UPPER LIMB FOR SPACE FLIGHT TASK BASED ON SIGNAL ANALYSES OF MULTIPLE MUSCLE FORCES

A novel healthy state monitor method of upper limb for space flight task is proposed. Without taking other complex diagnosis equipment in orbit, this method only uses the ordinary exercise instruments to collect and analyze the multiple muscle forces of astronauts, and deduces where the serious muscle atrophy occurs in their muscle groups of upper limb. First, the typical multiple muscle forces data of upper limb are accumulated. A 45-day 6-degree head-down tilt bed rest experiment together with a multiple muscle forces test experiment are carried out to collect the corresponding data. These data include both the muscle force data of healthy state and the related data of unhealthy state. Second, the Wavelet Packet Transform (WPT) and the Empirical Mode Decomposition (EMD) methods are used to compute the signal features of these data above. Third, a Support Vector Machine (SVM) classifier is trained by the related signal features. Finally, the trained SVM can be utilized to evaluate the healthy state of upper limb in orbit for astronaut. If the output of SVM is negative, the C-means method and the Euclidean distance can be used to locate the abnormal muscle forces and muscle groups. The concept of typical muscle group health state evaluation for upper limb is emphasized in this paper. The comparisons among the traditional diagnosis-based method, the electromyogram (EMG)-based muscle forces analysis method, and the proposed method are made. Many experiment results on ground have verified the effectiveness of proposed method.

Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise.

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle.