Head-down Tilt Bed Rest Research Articles

Simulating microgravity with 60 days of 6 degree head-down tilt bed rest compromises sleep

Astronauts in space often experience sleep loss. In the AGBRESA (Artificial Gravity Bed Rest) study, we examined 24 participants (mean age ± SD, 33 ± 9 years) during two months of 6o head-down tilt (HDT) bed rest, which is a well-established spaceflight analogue. Polysomnography was recorded during baseline (BDC-9), HDT (nights 1, 8, 30 and 58) and recovery (R, nights 1 and 12). Mixed ANOVAs with post-hoc step-down Bonferroni adjustment indicated that compared to BDC-9, arousals were increased, while sleep duration, N3, and sleep efficiency were all decreased during HDT. Significant quadratic associations between sleep duration and quality with time into HDT did not indicate adaptive improvements during the course of HDT. While sleep duration recovered quickly after the end of bed rest, participants still displayed protracted sleep fragmentation. We conclude that physiological changes caused by exposure to microgravity may contribute to persistent sleep deficits experienced during real space missions.

New insights into the impact of bed rest on lumbopelvic muscles: A computer-vision model approach to measure fat fraction changes.

Space agencies plan crewed missions to the Moon and Mars. However, microgravity-induced lumbopelvic deconditioning, characterized by an increased fat fraction (FF) due to reduced physical activity, poses a significant challenge to spine health. This study investigates the spatial distribution of FF in the lumbopelvic muscles to identify the most affected regions by deconditioning, utilizing a computer-vision model and a tile-based approach to assess FF changes. Twenty-four healthy individuals (8F) were recruited, and automatic segmentation of the lumbopelvic muscles was applied before and after 59 days of head-down tilt bed rest (HDTBR+59) and 13 days of reconditioning (R+13). Axial Dixon sequence images were acquired from 3T magnetic resonance imaging. FF in the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum, psoas major, gluteus maximus (GMax), gluteus medius (GMed) and gluteus minimus (GMin) muscles from the upper margin of L1 vertebra to the inferior border of GMax muscle were automatically derived using a computer-vision model. Lumbar muscles were segmented into eight tiles (superficial and deep, lateral to medial), and gluteal muscles into regions (anterior/superior for GMed and GMin, superior/inferior for GMax). At HDTBR+59, the deep centro-lateral region at L5/S1 for LM (18.7±15.7%, p<0.001; d=0.97) and the deep medial region at Upper L4 for LES (5.4±5.9%, p<0.001; d=0.34) showed the largest increase in FF compared to BDC. These regions did not recover at R+13 (p<0.05; d≥0.25). These findings highlight the need to target deep fascicles of LM and LES in countermeasure strategies to mitigate microgravity-induced lumbopelvic deconditioning, optimizing spine health and performance.

Artificial gravity: an effective countermeasure for microgravity-induced headward fluid shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine whether daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of 6° head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: no AG (control), daily 30-min intermittent AG (iAG), and daily 30-min continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3 T. MRI was performed at baseline, 14 and 52 days into HDTBR, and 3 days after HDTBR (recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared with baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps < 0.05). ICARI was only increased 14 days into HDTBR (P < 0.05). Neither iAG nor cAG significantly affected measurements compared with HDTBR alone, indicating that 30 min of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force, or both are suggested for future countermeasure research.NEW & NOTEWORTHY Brief exposure to continuous or intermittent artificial gravity via short-arm centrifugation was insufficient in mitigating the intracranial pathophysiological effects of the headward fluid shift simulated during head-down tilt bed rest (HDTBR). Our results suggest that greater centrifugation session duration, gravitational force, or both may be required to prevent the development of spaceflight-associated neuro-ocular syndrome and should be considered in future ground-based countermeasure studies.

Impact of Daily Lower-Body Negative Pressure or Cycling Followed by Venous Constrictive Thigh Cuffs on Bedrest-Induced Orthostatic Intolerance.

Orthostatic intolerance occurs following immobilization in patients on Earth and in astronauts after spaceflight. Head-down tilt bedrest is a terrestrial model for weightlessness and induces orthostatic intolerance. We hypothesized that lower-body negative pressure (LBNP) or cycling followed by wearing venous constrictive thigh cuffs mitigates orthostatic intolerance after head-down tilt bedrest. We enrolled 47 healthy individuals (20 women, 35±9 years) to a 30-day strict head-down tilt bedrest study. During bedrest, they were assigned to 6 hours of 25 mm Hg LBNP (n=12) per day and 1 hour of supine cycling followed by 6 hours of venous constriction through thigh cuffs 6 days per week (n=12), 6 hours of daily upright sitting (positive control, n=11), or no countermeasure (negative control, n=12). We measured orthostatic tolerance as the time to presyncope during 80° head-up tilt testing with incremental LBNP before and immediately after bedrest. We determined plasma volume with carbon monoxide rebreathing before and at the end of bedrest. After bedrest, orthostatic tolerance decreased 540±457 seconds in the control group, 539±68 seconds in the cycling group, 217±379 seconds in the LBNP group, and 289±89 seconds in the seated group (P<0.0001 time point, P=0.009 for group differences). Supine and upright heart rate increased in all groups following bedrest. Plasma volume was only maintained in the cycling group but decreased in all others (interaction countermeasure×time point P<0.0001). Six hours of moderate LBNP training was as effective as sitting in attenuating orthostatic intolerance after 30 days of head-down tilt bedrest. Daily cycling exercise followed by 6 hours of wearing venous constrictive thigh cuffs, while maintaining plasma volume, did not improve orthostatic tolerance. URL: https://www.bfarm.de/EN; Identifiers: DRKS00027643 and DRKS00030848.

Key Anabolic Markers in Human M. Soleus after 21-Day Head-Down Tilt Bedrest

Prolonged bed rest can have a significant negative effect on skeletal muscle, leading to muscle wasting and reduced strength. This process can occur in as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDT) is a method used to simulate the physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. This paper is dedicated to the analysis of key anabolic markers of the soleus muscle during 21 days of HDT BR. The HDT BR experiment was conducted at the Institute of Biomedical Problems, Russian Academy of Sciences. Six healthy male volunteers, aged 25–35 years, were subjected to 21 days of strict bed rest with a tilt angle of –6°. A needle biopsy of the m.soleus was performed using the Bergström method before the start of HDT BR and on day 21 of HDT BR. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. Examination of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDT BR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDT BR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDT BR.

The effect of 60days of 6° head-down-tilt bed rest on circulating adropin, irisin, retinol binding protein-4 (RBP4) and individual metabolic responses in young, healthy males.

Alterations in the circulating concentrations and target-tissue action of organokines underpin the development of insulin resistance in microgravity and gravity deprivation. The purpose of this study was to examine changes in circulating adropin, irisin, retinol binding protein-4 (RBP4), and the metabolic response of healthy young males following 60days of 6° head-down-tilt (HDT) bed rest, with and without reactive jump training (RJT), to explore links with whole-body and tissue-specific insulin sensitivity. To our knowledge, this is the first time that adropin, irisin, and RBP4 have been studied in HDT bed rest. A total of 23 male subjects (29 ± 6years, 181 ± 6cm, 77 ± 7kg) were exposed to 60days of 6° HDT bed rest and randomized to a control (CTRL, n = 11) or a RJT (JUMP, n = 12) group (48 sessions with ≤4min total training time per session). Circulating adropin, irisin, and RBP4 were quantified in fasting serum before and after HDT bed rest. A subanalysis was performed a posteriori to investigate individual metabolic responses post-HDT bed rest based on subjects that showed an increase or decrease in whole-body insulin sensitivity (Matsuda index). There were significant main effects of time, but not group, for decreases in adropin, irisin, Matsuda index, and liver insulin sensitivity following HDT bed rest (p < 0.05), whereas RBP4 did not change. The subanalysis identified that in a subgroup with decreased whole-body insulin sensitivity (n = 17), RBP4 increased significantly, whereas adropin, irisin, and liver insulin sensitivity were all decreased significantly following HDT bed rest. Conversely, in a subgroup with increased whole-body insulin sensitivity (n = 6), liver insulin sensitivity increased significantly after HDT bed rest, whereas adropin, irisin, and RBP4 did not change. Investigating individual metabolic responses has provided insights into changes in circulating adropin, irisin, RBP4, in relation to insulin sensitivity following HDT bed rest. We conclude that adropin, irisin, and RBP4 are candidate biomarkers for providing insights into whole-body and tissue-specific insulin sensitivity to track changes in physiological responsiveness to a gravity deprivation intervention in a lean male cohort.

Abstract P223: Impact Of Dynamic Or Static Training On Flow-Mediated Dilatation Following Prolonged Head-Down Tilt Bedrest

Cardiovascular deconditioning, cephalad fluid shifts, and altered sympathetic activity in weightlessness may elicit changes in vascular structure and function akin to vascular ageing. Head-down tilt bedrest is an established terrestrial model for weightlessness and elicits similar cardiovascular responses. We hypothesized that 30 days head-down tilt bedrest (HDTBR) worsens flow mediated dilation (FMD), a non-invasive endothelial function marker, and that daily orthostatic stimuli or physical exercise attenuates the response. Fourty-seven healthy individuals (20 women, age 35±9 years, BMI 23.7±2.6 kg/m 2 ) were assigned to 30 days of strict HDTBR and divided into four groups: Daily 6 hours of upright sitting (positive control, n=11); 6 hours of -25 mmHg lower body negative pressure (n=12); 60 minutes of supine cycling followed by 6 hours of thigh cuff venous occlusion 6 days per week (n=12), or no countermeasure (negative control, n=12). We measured upper arm blood pressure and heart rate 5 days before and immediately after bedrest. We assessed plasma volume by carbon monoxide-rebreathing 2 days before and on day 28 of bedrest. We determined FMD of the brachial artery 5 days before, on day 28 of bedrest, and after 13-day recovery. We collected blood samples to measure pro- and anti-inflammatory cytokines. Heart rate was elevated after bedrest (p&lt;0.0001) but remained constant in seated and cycling groups (seated MD 5±2 /min, cycling MD 5±2, p=0.0051). Systolic blood pressure increased in all groups (MD 4±1 mmHg, p=0.0004). Diastolic blood pressure was higher post-bedrest in the control group (MD 8±2 mmHg, p=0.0002) but remained constant in the countermeasure groups. Plasma volume was reduced after bed rest (MD -400±37 ml, p&lt;0.0001) but maintained in the cycling group (MD 147±72 ml, p=0.0001). FMD did not differ between groups, but was higher at bedrest (MD 1.9±0.8 %, p=0.0481), whereas recovery values did not differ from baseline. Resting brachial artery diameter tended to be higher at bedrest (p=0.0876). Cytokines revealed no clinically relevant inflammatory response. Head-down tilt bedrest-induced cardiovascular deconditioning, which was not completely abolished by any countermeasure, paradoxically increased flow-mediated brachial vasodilation. Additional cardiovascular risk factors may be required to express endothelial dysfunction in the face of reduced physical activity.

Liquid-alloy-based dual sensing elements contact lens sensor for continuous intraocular pressure monitoring

Intraocular pressure (IOP) fluctuation is an independent risk factor for glaucoma and a key to clarify its pathogenesis. We have developed a contact lens integrated with a conformal LC resonance circuit made of liquid alloy (Galinstan) for non-invasive continuous IOP monitoring. The contact lens is fabricated using polydimethylsiloxane (PDMS), in which the LC resonance circuit can sense corneal strain proportionally caused by IOP variation. The Galinstan configuration is formed to the designed pattern by UV-laser treating the carbon-doped Ecoflex (c-Ecoflex) stamps and then selectively transferring the Galinstan onto the stamp to form the LC resonance circuit pattern. The tests conducted on silicone model eyes demonstrate high sensitivity in the frequency responses to variations in IOP, reaching 649 ppm/mmHg. IOP measurement on human eyes during head-down tilt bedrest confirms its applicability. With process optimization, this contact lens sensor has great potential for mass production and wide application in monitoring IOP.

Effect of artificial gravity on neurocognitive performance during head-down tilt bedrest

This study evaluated the acute and chronic effects of intermittent and continuous Artificial Gravity (AG) on cognitive performance during 60 days of Head-down tilt bedrest (HDTBR), a well-established ground-based spaceflight analogue method. Participants were randomly assigned to three groups: intermittent AG, continuous AG, and HDTBR control group without AG exposure. Task performance and electrophysiological measures of attention and working memory were investigated during Simple and Complex tasks in the Visual and the Auditory modality. Compared to baseline, faster reaction time and better accuracy was present during HDTBR regarding the Complex tasks, however, the practice effect was diminished in the three HDTBR groups compared to an ambulatory control group. Brain potentials showed a modality-specific decrease, as P3a was decreased only in the Auditory, while P3b decreased in the Visual modality. No evidence for acute or chronic AG-related cognitive impairments during HDTBR was found.

Daily use of veno-constrictive thigh cuffs during 30 days of strict 6° head-down tilt bedrest to reverse the headward fluid shift

Introduction: Chronic exposure to weightlessness induces a persistent headward fluid shift, which may contribute to the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). Strict 6° head-down tilt bedrest (HDTBR) is a spaceflight analog that induces a headward fluid shift and development of SANS findings, enabling the evaluation of potential countermeasures. Lower body exercise can induce a sustained post-exercise hyperemia thereby shifting blood away from the central circulation. In addition, veno-constrictive thigh cuffs (VTC) can sequester blood volume in the legs. The purpose of this study was to determine whether 6 hours of daily VTC use following cycling exercise (Ex+VTC) could reverse the headward fluid shift during 30 days of strict 6° HDTBR. We hypothesized that Ex+VTC would sequester fluid in the legs leading to increased thigh circumference and reduced stroke volume (SV), cardiac output (CO), internal jugular vein (IJV) cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Methods: Participants were randomly assigned to a Control (n=12, 6 female) or Ex+VTC (n=12, 4 female) group and completed baseline data collection (BDC) in the seated and supine posture followed by 30 days of strict 6° HDTBR. The Ex+VTC group completed a maximal exercise test on a cycle ergometer in 6° HDT posture during BDC to establish work rates during HDTBR. The Ex+VTC group performed 10 minutes of light cycle exercise, cycled for 45 minutes at 45% of their max wattage, and then donned VTC to ~50 mmHg for 6 hours on 6 of 7 days per week during HDTBR. Data were collected before exercise and 30 minutes and 6 hours after exercise and donning VTCs on days 3, 17, and 29 of HDTBR. Controls were studied at similar time points. Days were nested within the models. Mixed models were used to determine differences between groups in the change in thigh circumference measured using a flexible tape measure, bilateral IOP measured using tonometry, CO measured using the inert gas rebreathe technique (Innocor), and ultrasound of bilateral IJV CSA and pressure from before to 30 min and 6 hours after use of the countermeasure. Left and right IJV and IOP data were nested within each participant. Results: The Ex+VTC group completed all exercise sessions followed by 6 hours of VTC use. Compared to Control, thigh circumference was greater after 30 minutes (+1.3 vs. -0.2 cm, p&lt;0.001) and 6 hours of VTC use (+2.5 cm vs. -0.1 cm in controls, p&lt;0.001). SV (-38 vs. 2 ml, p&lt;0.001) and CO (-1.5 vs. 0.3 L/min, p&lt;0.001) were reduced at 30 minutes and 6 hours of VTC use (SV: -30 vs. 5 ml, p&lt;0.001; CO: -1.1 vs. 0.6 L/min, p&lt;0.001) compared to Control. IJV CSA and pressure were reduced at 30 minutes (CSA, p&lt;0.001; pressure, p=0.001) and 6 hours of VTC use (CSA, p&lt;0.001; pressure, p=0.007). IOP was not different compared to Control. Conclusions:Use of VTC for 6 hours after 45 minutes of exercise successfully sequestered fluid in the legs, leading to a reduction in central blood volume, IJV CSA, and IJV pressure. Thus, an Ex+VTC countermeasure resulted in a partial fluid shift reversal. This research was supported by the NASA Human Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

INFLUENCES OF BEDREST DECONDITIONING ON ORTHOSTATIC HYPERTENSION RISK

Objective: Orthostatic hypertension defined as systolic blood pressure (SBP) increase of more than 20 mmHg when standing up with hypertensive upright SBP heralds increased cardiovascular risk. The phenomenon is caused by sympathetic overactivation and occurs in conditions associated with poor cardiopulmonary fitness or hypovolemia. We hypothesized that head-down tilt bedrest, which induces cardiopulmonary deconditioning, hypovolemia, and sympathetic activation increases the likelihood of experiencing orthostatic hypertension. Design and method: We pooled data from two strict head-down tilt bedrest studies, the 60 days AGBRESA study (n=24, 8 women/ 16 men, 33.3±9 years) and the 30 days SANS countermeasure study (n=47, 20 women/ 27 men, 35±9 years), which both included healthy persons on no medications. In both studies, participants were on controlled sodium diets and caloric intake was adjusted to maintain body weight. Before and immediately after bedrest, we measured supine and upright blood pressure and heart rate during head-up tilt testing. We measured plasma volume using carbon monoxide rebreathing before and after bedrest. Results: Supine SBP was 128±9 mmHg before and 133±10 mmHg after bedrest (p&lt;0.0001). While 5 minutes standing, SBP changed 2±8 mmHg before and 3±8 mmHg after bedrest (p=0.5825). 1 out of 67 participants fulfilled diagnostic criteria of orthostatic hypertension before and 3 out of 57 after bedrest. Supine heart rate was 69±11 bpm before and 79±15 bpm after bedrest (p&lt;0.0001). With standing, heart rate increased 21±12 bpm before and 39±16 bpm after bedrest (p&lt;0.0001). Plasma volume decreased by 367±348 ml with bedrest (p&lt;0.0001). Conclusions: We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to elicit orthostatic hypertension. There may be a smaller subgroup of susceptible individuals.

Key Anabolic Markers in Human Soleus Muscle after 21-Day Head-Down Tilt Bed Rest

Key Anabolic Markers in Human Soleus Muscle after 21-Day Head-Down Tilt Bed Rest

Potential Biomarkers of Resilience to Microgravity Hazards in Astronauts.

Space exploration exposes astronauts to the unique environment of microgravity, which poses significant health challenges. Identifying biomarkers that can predict an individual's resilience to the stressors of microgravity holds great promise for optimizing astronaut selection and developing personalized countermeasures. This narrative review examines the principal health risks associated with microgravity and explores potential biomarkers indicative of resilience. The biomarkers being evaluated represent a broad spectrum of physiological domains, including musculoskeletal, neurological, immunological, gastrointestinal, cardiovascular, and cutaneous systems. Earth-based microgravity analogs, such as dry immersion and head-down tilt bed rest, may provide valuable platforms to validate candidate biomarkers. However, biomarker sensitivity and specificity must be further evaluated to ensure efficacy and reliability. Establishing a panel of biomarkers predictive of resilience to microgravity-induced health risks would significantly enhance astronaut health and mission success, especially for long-duration exploration missions. Insights gained may also translate to health conditions on Earth characterized by reduced physical activity and mechanical loading.

Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

Effects of 30 days bed rest and exercise countermeasures on PBMC bioenergetics.

Altered mitochondrial function across various tissues is a key determinant of spaceflight-induced physical deconditioning. In comparison to tissue biopsies, blood cell bioenergetics holds promise as a systemic and more readily accessible biomarker, which was evaluated during head-down tilt bed rest (HDTBR), an established ground-based analog for spaceflight-induced physiological changes in humans. More specifically, this study explored the effects of HDTBR and an exercise countermeasure on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). We subjected 24 healthy participants to a strict 30-day HDTBR protocol. The control group (n = 12) underwent HDTBR only, while the countermeasure group (n = 12) engaged in regular supine cycling exercise followed by veno-occlusive thigh cuffs post-exercise for 6 h. We assessed routine blood parameters 14 days before bed rest, the respiratory capacity of PBMCs via high-resolution respirometry, and citrate synthase activity 2 days before and at day 30 of bed rest. We confirmed PBMC composition by flow cytometry. The change of the PBMC maximal oxidative phosphorylation capacity (OXPHOS) amounted to an 11% increase in the countermeasure group, while it decreased by 10% in the control group (p = 0.04). The limitation of OXPHOS increased in control only while other respiratory states were not affected by either intervention. Correlation analysis revealed positive associations between white blood cells, lymphocytes, and basophils with PBMC bioenergetics in both groups. This study reveals that a regular exercise countermeasure has a positive impact on PBMC mitochondrial function, confirming the potential application of blood cell bioenergetics for human spaceflight.

Quantitative ultrasound image assessment of the optic nerve subarachnoid space during 90-day head-down tilt bed rest

The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P < 0.001), respectively, and recovered immediately after HDT on R + 2. Such small changes in the ONSSA were below the lateral resolution limit of ultrasound (0.4 mm) and may not be clinically relevant, possibly due to ONS hysteresis causing persistent ONS distension. Future research can explore advanced quantitative portable ultrasound-based techniques and establish comparisons containing the pre-HDT measurements to deepen our understanding of SANS.

Effects of intermittent seating upright, lower body negative pressure, and exercise on functional tasks performance after head-down tilt bed rest.

Bed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects' performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts' balance control systems immediately after they return from space. Forty-seven participants were assessed before and a few hours after 30days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30days; b) sat upright for 6h a day; c) were exposed to lower body negative pressure (LBNP) for 6h a day; or d) exercised for 60min and then wore venous-occlusive cuffs for 6h a day. Results showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them. These data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.

State of the Retina and Optic Nerve in 21-Day Head-Down Tilt Bed Rest

State of the Retina and Optic Nerve in 21-Day Head-Down Tilt Bed Rest