Days Of Head-down Bed Rest Research Articles

Biological Sex Modestly Influences the Impact of Long Duration Bed Rest on Human Sympathetic Neurocirculatory Regulation

Our understanding regarding the impact of simulated microgravity on sympathetic neurocirculatory regulation, and the modulatory effects of biological sex, remain incomplete. Through retrospective analysis of two long-duration bed rest trials, this study investigated the impact of 60 days of -6° head-down bed rest (HDBR) on the transduction of integrated muscle sympathetic nerve activity (MSNA; peroneal microneurography) into mean arterial pressure (MAP; Finometer) in healthy females ( n = 12, 25-40 years) and males ( n = 13, 21-42 years). Signal averaging quantified sympathetic transduction for 12 cardiac cycles (ECG) following integrated MSNA bursts. The transduction of integrated MSNA bursting patterns was studied based on the overall response, temporal burst firing patterns (singlet, doublet, and triplet+), and burst amplitude (binned into quartiles: Q1-Q4). Data are reported as mean (SD) for a 5-minute baseline period pre-HDBR and post-HDBR. Statistical analysis included mixed-effect analyses with post-hoc t-tests. In the pooled analyses, HDBR reduced the overall MAP transduction response to integrated MSNA bursts (pre-HDBR: 1.4 ± 0.5 mmHg, post-HDBR: 1.1 ± 0.4 mmHg; P = 0.003). This stemmed from attenuated MAP transduction responses to small- and medium-sized bursts (i.e., Q1-Q3) but there was no effect of HDBR on the largest bursts (i.e., Q4: pre-HDBR: 2.2 ± 0.9 mmHg, post-HDBR: 2.1 ± 0.9 mmHg; P = 0.59). HDBR did not affect the transduction response to singlets (P = 0.23), but HDBR reduced the MAP transduction responses to doublets and triplets+ (both P < 0.03). HDBR did not affect the reduction in MAP during non-bursting periods (pre-HDBR: -0.5 ± 0.2 mmHg, post-HDBR: -0.4 ± 0.2 mmHg; P = 0.17). When stratifying the analyses by sex, we observed that HDBR reduced the overall MAP transduction response to integrated MSNA bursts more so in males (P < 0.01) than females (P = 0.14). Conversely, HDBR did not affect the MAP reductions following non-bursting periods in males (P = 0.53), but in females the reduction in MAP following non-bursting periods was less after HDBR, particularly for cardiac cycles 5 to 7 (pre-HDBR: -0.8 ± 0.5 mmHg, post-HDBR: -0.5 ± 0.3 mmHg; P = 0.03). These data suggest that 60 days of HDBR attenuates sympathetic neurocirculatory regulation during baseline conditions, with a modest influence of biological sex. This work was supported by the Canadian Space Agency, Centre National d'Etudes Spatiales, European Space Agency, National Aeronautics and Space Administration, Institute of Aerospace Medicine of the German Aerospace Center (DLR), Fond Européen de Développement Régional (FEDER) and the Natural Sciences and Engineering Research Council of Canada (NSERC). 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.

Exercise training mitigates the deleterious effects of experimental bed rest on intraindividual variability of executive functioning in older adults: A randomised controlled trial

AbstractBackgroundIn older adults, bed rest can occur because of chronic conditions, injury, surgery, or hospitalization. Extreme levels of physical inactivity due to bed rest initiate a downward spiral in several body systems. Exercise is a countermeasure to many of these changes; nonetheless, little is known about the effect of exercise on older adults’ cognition during bed rest. We thus examined the effects of exercise on the intraindividual variability (IIV) of cognitive performance in older adults exposed to 14 days of experimental 6° head‐down bed rest (HDBR) and whether sex moderates its effects. We chose IIV as our outcome measure because it is more sensitive than traditional summary scores of cognitive performance, albeit no studies have explored exercise effects on older adults’ IIV submitted to bed rest.MethodA non‐blinded, parallel‐group, randomised controlled trial. Twenty‐three healthy older adults aged 55‐65 were randomised to: 1) 14 days of HDBR (CON); or 2) 14 days of HDBR with daily aerobic and strength exercise (EX). Data were collected at baseline, HDBR completion, and end of seven‐day‐recovery. The National Institutes of Health Toolbox Cognitive Battery assessed executive function (Flanker Incongruent and Congruent and Dimensional Change Card Sort) and processing speed (Pattern Comparison). IIV was indexed by intraindividual coefficient of variation (ICV) and residual intraindividual standard deviation (R‐ISD), with R‐ISD as our primary measure of interest. Linear mixed models assessed group differences and the moderator role of sex.ResultAt HDBR completion, EX had significantly lower (better) Flanker incongruent ICV (Estimated mean difference = ‐0.10, 95%CI ‐0.19;‐0.003, p = 0.022) and R‐ISD (Estimated mean difference = ‐3.63, 95%CI ‐6.10;‐1.17, p = 0.005) vs. CON. Sex moderated the effect of exercise; females in EX had significantly lower Flanker incongruent ICV vs. CON (Estimated mean difference = ‐0.23; 95%CI ‐0.34;‐0.12, p<0.001). At the end of the seven‐day recovery, EX had significantly lower Flanker incongruent R‐ISD vs. CON (Estimated mean difference = ‐3.11, 95%CI ‐5.70;‐0.052, p = 0.019). Summary scores and processing speed IIV changes were not statistically significant (ps>0.05).ConclusionExercise during HDBR preserved executive functioning, especially in females. Our findings support the delivery of exercises to older adults during bed rest to preserve their cognitive function.

Are changes in muscular strength following head‐down bed rest independently associated with improved cognitive function in older adults? A secondary analysis of a randomized controlled trial

AbstractBackgroundPhysical inactivity is common among older adults and is a risk factor for cognitive decline. Even a brief period of physical inactivity, such as bed rest due to hospitalization, in older adults has significant negative impacts. Exercise is strategy to counter the negative effects of physical inactivity. Exercise‐induced improvements in cardiorespiratory fitness is associated with improved cognitive function. Less is known regarding the contribution of exercise‐induced changes in muscle strength to changes in cognitive function. Thus, we aimed to examine the independent contribution of: 1) change in cardiorespiratory fitness; and 2) change in peak muscle torque of the lower extremity to changes in cognitive function in a randomized controlled trial (RCT) of head‐down bed rest (HDBR) vs. HDBR with exercise in healthy older adults.MethodAn analysis of a non‐blinded, parallel‐group, RCT of 22 healthy older adults (11 males and 11 females) aged 55‐65 years. Participants were randomized to: 1) 14 days of 6° HDBR (CON); or 2) HDBR with daily resistance and aerobic exercise training (EX). Outcome measures were taken at baseline and HDBR completion. The Flanker Inhibitory Control and Attention Task measured executive function. Physical fitness measures included: 1) maximal aerobic capacity (VO2max) using a bicycle ergometry test; and 2) knee extension isokinetic muscular strength (KE) using a Biodex dynamometer. We performed two separate multiple linear regressions to determine whether following 14 days of HDBR: 1) VO2max was associated with Flanker score, after accounting for ΔKE; and 2) KE was associated with Flanker score, after accounting for ΔVO2max. Each model was also adjusted for baseline Flanker score and the baseline physical fitness measure of interest.ResultAt baseline, average Flanker t‐score was 48.33, mean VO2max was 32.527 ml/kg/min, and knee extension strength was 64.472 Nm. VO2max at follow‐up was not significantly associated with Flanker performance (b = 0.232 ± 0.716; p = 0.635; R2 adj. = 0.285). However, greater KE strength was significantly associated with better Flanker performance (b = 2.023 ± 0.389; p = 0.043; R2 adj. = 0.633) at HDBR completion.ConclusionThe maintenance of muscle strength even during brief periods of physical inactivity appears to be critical for cognitive health in older adults.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures

Introduction: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. Methods: Twenty-three participants (12 males and 11 females), aged 55–65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. Results: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. Conclusion: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Effects of Posture and Walking on Tibial Vascular Hemodynamics Before and After 14 Days of Head-Down Bed Rest.

Human skeletal hemodynamics remain understudied. Neither assessments in weight-bearing bones during walking nor following periods of immobility exist, despite knowledge of altered nutrient-artery characteristics after short-duration unloading in rodents. We studied 12 older adults (8 females, aged 59 ± 3 years) who participated in ambulatory near-infrared spectroscopy (NIRS) assessments of tibial hemodynamics before (PRE) and after (POST) 14 days of head-down bed rest (HDBR), with most performing daily resistance and aerobic exercise countermeasures during HDBR. Continual simultaneous NIRS recordings were acquired over the proximal anteromedial tibial prominence of the right lower leg and ipsilateral lateral head of the gastrocnemius muscle during supine rest, walking, and standing. During 10 minutes of walking, desaturation kinetics in the tibia were slower (time to 95% nadir values 125.4 ± 56.8 s versus 55.0 ± 30.1 s, p = 0.0014). Tibial tissue saturation index (TSI) immediately fell (-9.9 ± 4.55) and did not completely recover by the end of 10 minutes of walking (-7.4 ± 6.7%, p = 0.027). Upon standing, total hemoglobin (tHb) kinetics were faster in the tibia (p < 0.0001), whereas HDBR resulted in faster oxygenated hemoglogin (O2Hb) kinetics in both tissues (p = 0.039). After the walk-to-stand transition, changes in O2Hb (p = 0.0022) and tHb (p = 0.0047) were attenuated in the tibia alone after bed rest. Comparisons of NIRS-derived variables during ambulation and changes in posture revealed potentially deleterious adaptations of feed vessels after HDBR. We identify important and novel tibial hemodynamics in humans during ambulation before and after bed rest, necessitating further investigation. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Impact of 60 days of head-down bed rest on large arteries.

The long-term cardiovascular consequences of microgravity on large arteries are a threat for long-term space missions. We hypothesized that changes in arterial properties differ according to the arterial territory (upper or lower body), and arterial structure (elastic vs. muscular arteries), in response to 60-day head-down bed rest (HDBR). Twenty healthy male volunteers were included and received a daily multivitamin supplementation in a double-blind fashion. At baseline, 29 and 52 days during strict HDBR, then 12 and 30 days after HDBR, aortic stiffness was measured using carotid-to-femoral pulse wave velocity (cf-PWV) and aortic MRI. Carotid, femoral, brachial and popliteal arteries were studied by ultrasound echo tracking, central blood pressure (BP) by tonometry and endothelial function by flow-mediated dilatation. Cf-PWV increased during HDBR (+0.8 and +1.1m/s, at D29 and D52, respectively, P = 0.004), corresponding to an increase in vascular age up to +11 years (P = 0.003). Changes were similar to those observed on MRI (+0.8 m/s at D52, P < 0.01) and were independent of BP and heart rate changes. After HDBR, cf-PWV showed a substantial recovery at R12 but still remained higher than baseline at R30 (+0.8 m/s, P = 0.018), corresponding to +6.5 years of vascular aging (P = 0.018). Thoracic aorta diameter increased significantly (+6%, P = 0.0008). During HDBR, femoral and popliteal arteries showed dimensional changes, leading to femoral inward hypotrophic remodeling (femoral diameter: -12%, P < 0.05; wall cross-sectional area: -25%, P = 0.014) and popliteal inward eutrophic remodeling (popliteal diameter: -25%, P < 0.05; wall cross-sectional area: -3%, P = 0.51). After HDBR, both arterial territories of the leg recovered. We did not observe any significant changes for carotid arteries nor for endothelial function during and after HDBR. Multivitamin supplementation did not affect vascular changes. HDBR was associated with an important increase in aortic stiffness, which did not completely recover 1 month after the end of HDBR. The thoracic aorta and the lower body muscular arteries underwent significant changes in dimensions whereas the common carotid arteries were preserved. These results should raise caution for those exposed to microgravity, real or simulated.

Non-Invasive Skin Imaging Assessment of Human Stress During Head-Down Bed Rest Using a Portable Handheld Two-Photon Microscope.

Spaceflight presents a series of physiological and pathological challenges to astronauts resulting from ionizing radiation, microgravity, isolation, and other spaceflight hazards. These risks cause a series of aging-related diseases associated with increased oxidative stress and mitochondria dysfunction. The skin contains many autofluorescent substances, such as nicotinamide adenine dinucleotide phosphate (NAD(P)H), keratin, melanin, elastin, and collagen, which reflect physiological and pathological changes in vivo. In this study, we used a portable handheld two-photon microscope to conduct high-resolution in vivo skin imaging on volunteers during 15 days of head-down bed rest. The two-photon microscope, equipped with a flexible handheld scanning head, was used to measure two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) images of the left forearm, left front chest, and forehead of volunteers. Changes in TPEF, SHG, and the extended SHG-to-AF(TPEF) aging index of the dermis (SAAID) were measured. It was found that TPEF intensity increased during bed rest and was restored to normal levels after recovery. Meanwhile, SHG increased slightly during bed rest, and the skin aging index increased. Moreover, we found the skin TPEF signals of the left forearm were significantly negatively associated with the oxidative stress marker malondialdehyde (MDA) and DNA damage marker 8-hydroxy-2′-desoxyguanosine (8-OHdG) values of subjects during head-down bed rest. Meanwhile, the SHG signals were also significantly negatively correlated with MDA and 8-OHDG. A significant negative correlation between the extended SAAID of the left chest and serum antioxidant superoxide dismutase (SOD) levels was also found. These results demonstrate that skin autofluorescence signals can reflect changes in human oxidant status. This study provides evidence for in-orbit monitoring of changes in human stress using a portable handheld two-photon microscope for skin imaging.

Effects of Resistance Exercise with or without Whey Protein Supplementation on Ocular Changes after a 21-Day Head-Down Bed Rest.

Neuro-ophthalmological changes have been reported after prolonged exposure to microgravity; however, the pathophysiology remains unclear. The objectives of the present study were twofold: (1) to assess the neuro-ophthalmological impact of 21 days of head-down bed rest (HDBR) and (2) to determine the effects of resistance vibration exercise (RVE) alone or combined with nutritional supplementation (NeX). In this case, 12 healthy male subjects completed three interventions of a 21-day HDBR: a control condition without countermeasure (CON), a condition with resistance vibration exercise (RVE) comprising of squats, single leg heel and bilateral heel raises and a condition using also RVE associated with nutritional supplementation (NeX). Intraocular pressure (IOP) was assessed by applanation tonometry. Retinal nerve fiber layer thickness (RNFLT) was assessed with spectral-domain optical coherence tomography, before HDBR and between Day 2 and Day 4 after each session of HDBR. In CON condition, IOP was preserved; while in RVE and NeX conditions, IOP was increased. In CON condition, RNFLT was preserved after HDBR. RVE and NeX conditions did not have significant effects on RNFLT. This study showed that a 3-week HDBR did not induce significant ophthalmological changes. However, RVE induced an elevation in IOP after HDBR. Nutritional supplementation did not reduce or exacerbate the side effects of RVE.

Effect of jump exercise training on long-term head-down bed rest-induced cerebral blood flow responses in arteries and veins.

What is the central question of this study? What is the effect of an exercise countermeasure on microgravity-induced change in cerebral blood flow? What is the main finding and its importance? Jump exercise training as a countermeasure did not modify the heterogeneous cerebral blood flow response to head-down bed rest, suggesting that this method is effective in preventing cardiovascular system deconditioning but is not good for cerebral haemodynamics. This study aimed to examine the effect of an exercise countermeasure on cerebral blood flow (CBF) response to long-term -6° head-down bed rest (HDBR) in all cerebral arteries and veins. Twenty male volunteers were exposed to HDBR for 60days with (training group, n=10) or without (control group, n=10) jump exercise training as a countermeasure to spaceflight. The blood flow in the neck conduit arteries (internal carotid and vertebral artery; ICA and VA) and veins (internal jugular and vertebral veins; IJV and VV) was measured, using ultrasonography before (baseline) HDBR, on the 30th and 57th day of HDBR. Long-term HDBR causes a heterogeneous CBF response between the anterior and the posterior brain or between arteries and veins. Long-term HDBR decreased anterior cerebral arterial and venous blood flow, while posterior cerebral arterial and venous blood flows were well maintained. However, exercise jump training did not change each arterial and venous CBF responses to HDBR (control vs. training; ICA, P=0.643; VA, P=0.542; external carotid artery, P=0.644; IJV, P=0.980; VV, P=0.999). These findings suggest that jump exercise training did not modify the heterogeneous CBF response to long-term HDBR.

Evaluation of Cardiac Circadian Rhythm Deconditioning Induced by 5-to-60 Days of Head-Down Bed Rest.

Head-down tilt (HDT) bed rest elicits changes in cardiac circadian rhythms, generating possible adverse health outcomes such as increased arrhythmic risk. Our aim was to study the impact of HDT duration on the circadian rhythms of heart beat (RR) and ventricular repolarization (QTend) duration intervals from 24-h Holter ECG recordings acquired in 63 subjects during six different HDT bed rest campaigns of different duration (two 5-day, two 21-day, and two 60-day). Circadian rhythms of RR and QTend intervals series were evaluated by Cosinor analysis, resulting in a value of midline (MESOR), oscillation amplitude (OA) and acrophase (φ). In addition, the QTc (with Bazett correction) was computed, and day-time, night-time, maximum and minimum RR, QTend and QTc intervals were calculated. Statistical analysis was conducted, comparing: (1) the effects at 5 (HDT5), 21 (HDT21) and 58 (HDT58) days of HDT with baseline (PRE); (2) trends in recovery period at post-HDT epochs (R) in 5-day, 21-day, and 60-day HDT separately vs. PRE; (3) differences at R + 0 due to bed rest duration; (4) changes between the last HDT acquisition and the respective R + 0 in 5-day, 21-day, and 60-day HDT. During HDT, major changes were observed at HDT5, with increased RR and QTend intervals’ MESOR, mostly related to day-time lengthening and increased minima, while the QTc shortened. Afterward, a progressive trend toward baseline values was observed with HDT progression. Additionally, the φ anticipated, and the OA was reduced during HDT, decreasing system’s ability to react to incoming stimuli. Consequently, the restoration of the orthostatic position elicited the shortening of RR and QTend intervals together with QTc prolongation, notwithstanding the period spent in HDT. However, the magnitude of post-HDT changes, as well as the difference between the last HDT day and R + 0, showed a trend to increase with increasing HDT duration, and 5/7 days were not sufficient for recovering after 60-day HDT. Additionally, the φ postponed and the OA significantly increased at R + 0 compared to PRE after 5-day and 60-day HDT, possibly increasing the arrhythmic risk. These results provide evidence that continuous monitoring of astronauts’ circadian rhythms, and further investigations on possible measures for counteracting the observed modifications, will be key for future missions including long periods of weightlessness and gravity transitions, for preserving astronauts’ health and mission success.

Влияние гипоксических тренировок на ортостатическую устойчивость человека до и после моделированной микрогравитации

Reduced orthostatic tolerance (OT) is a serious concern facing space medicine. This work sought to evaluate the effects of intermittent hypoxic training (IHT) on OT in humans before and after 3 days of head-down bed rest (HDBR) used to model microgravity. The study was carried out in 16 male volunteers aged 18 to 40 years and included 2 series of experiments with 11-day and 21-day IHT administered on a daily basis. During the first IHT session, the concentration of oxygen in the inspired gas mixture was 10%; for other sessions it was adjusted to 9%. OT was assessed by a 20-minute-long orthostatic tilt test (OTT) conducted before and after HDBR. Before HDBR, orthostatic intolerance was observed in 3 participants, while after HDBR, it was observed in 9 of 16 volunteers (p &lt; 0.05). During OTT conducted after HDBR, the heart rate (HR) exceeded control values by 26.8% (p &lt; 0.01). Preexposure to any of the applied IHT regimens led to a reduction in the number of volunteers with orthostatic intolerance. After the 11-day IHT program, there was a less pronounced increase in HR during OTT before HDBR; with the extended IHT regimen, less pronounced changes were observed for HR, systolic, diastolic and mean blood pressure (BP). The increase in HR during OTT after HDBR was significantly lower in the group that had completed the 11-day IHT program, while BP remained stable. The changes in HR and systolic BP were less pronounced in the group that had completed the 21-day IHT program than in the control group (p &lt; 0.05). Thus, IHT reduced the risk of orthostatic disorders and mitigated changes in cardiovascular parameters during the orthostatic test.

Exercise and Testosterone Countermeasures to Mitigate Metabolic Changes during Bed Rest

Background/Objectives: Exercise is a front-line countermeasure used to maintain astronaut health during long-duration spaceflight; however, reductions in metabolic health still occur. Accordingly, we evaluated serial changes in metabolic parameters in a spaceflight analog and evaluated the efficacy of exercise with or without the addition of low-dose testosterone treatment on mitigating adverse metabolic changes. Subjects/Methods: Healthy young (<55 years) men were randomly assigned to one of three groups during 70-days of strict, diet controlled, 6° head-down bed rest: Control (CON, n=9), exercise plus testosterone countermeasure (TEX, n=8), or exercise countermeasure plus placebo (PEX, n=9). Basal metabolic rate (BMR), glucose tolerance, and insulin sensitivity were measured before, during, and after bed rest. Exercise energy expenditure and excess post-exercise oxygen consumption were measured in TEX and PEX subjects during bed rest. Results: Leptin decreased during bed rest (Pre to BR+0 changed from 6.9 ± 5.1, 5.8 ± 4.2, and 4.7 ± 4.1 to 7.9 ±3.6, 6.5 ± 4.6, and 4.1 ±3.0 ug• L−1 for CON, PEX, and TEX respectively). Bed rest induced a decrease in BMR (Pre to BR57 changed from 1655 ± 212, 1629 ± 108, and 1706 ± 146 to 1476 ± 166, 1668 ± 142, and 1603 ± 132 kcal • day−1 ± 95%CI for CON, PEX, and TEX respectively). Similarly, bed rest negatively affected glucose metabolism assessed by 2hr OGTT glucose (Pre to BR66 changed from 6.29 ± 0.72, 5.13 ± 0.72, and 5.87 ± 0.73 to 6.62 ± 0.72, 5.83 ± 0.72, and 7.08 ± 0.72 mmol • L−1 ± 95%CI). Reambulation following bed rest positively affected glucose tolerance in CON (2hr OGTT glucose at BR+12: 5.3 ± 0.72, 6.42 ± 0.73, and 6.04 ± 0.73 mmol • L−1 ± 95%CI). Testosterone protected against bed rest induced insulin resistance (HOMA-IR from Pre to BR+66 changed from 1.74 ± 0.54, 1.18 ± 0.55, and 1.45 ± 0.56 to 2.24 ± 0.56, 1.47 ± 0.54, and 1.07 ± 0.54). Conclusion: This study confirmed that inactivity during 70 days of head-down bed rest adversely affects metabolic health. The daily exercise countermeasures were beneficial but not completely protective of bed rest induced decrements in metabolic health. Supplementary countermeasures such as testosterone may provide additional benefits not provided by exercise alone.

Circulating MicroRNA Expression and Serum Biomarker Changes After 30 Days of Head-Down Bed Rest

Circulating MicroRNA Expression and Serum Biomarker Changes After 30 Days of Head-Down 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.

Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle Atrophy.

Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs) could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499) were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR). The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression.

Electromyography-based analysis of human upper limbs during 45-day head-down bed-rest

Muscle deconditioning occurs in response to simulated or actual microgravity. In spaceflight, astronauts become monkey-like for mainly using their upper limbs to control the operating system and to complete corresponding tasks. The changes of upper limbs׳ athletic ability will directly affect astronauts’ working performance. This study investigated the variation trend of surface electromyography (sEMG) during prolonged simulated microgravity. Eight healthy males participating in this study performed strict 45-day head-down bed-rest (HDBR). On the 5th day of pre-HDBR, and the 15th, the 30th and the 45th days of HDBR, the subjects performed maximum pushing task and maximum pulling task, and sEMG was collected from upper limbs synchronously. Each subject’s maximum volunteer contractions of both the tasks during these days were compared, showing no significant change. However, changes were detected by sEMG-based analysis. It was found that integrated EMG, root mean square, mean frequency, fuzzy entropy of deltoid, and fuzzy entropy of triceps brachii changed significantly when comparing pre-HDBR with HDBR. The variation trend showed a recovery tendency after significant decline, which is inconsistent with the monotonic variation of lower limbs that was proved by previous research. These findings suggest that EMG changes in upper limbs during prolonged simulated microgravity, but has different variation trend from lower limbs.

Transcutaneous electrical acupuncture stimulation as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans.

ObjectiveSpaceflight is associated with cardiovascular deregulation. However, the influence of microgravity on the cardiovascular system and its mechanisms and countermeasures remain unknown. Our previous studies have demonstrated that transcutaneous electrical acupuncture stimulation (TEAS) is effective in improving orthostatic tolerance (OT). The purpose of this study was to determine if TEAS treatment can attenuate cardiovascular deconditioning induced by a 4-day −6° head-down bed rest (HDBR).MethodsFourteen healthy male subjects were randomly allocated to a control group (control, n=6, 4 days HDBR without countermeasures) and a TEAS treatment group (TEAS, n=8, 4 days HDBR with TEAS at Neiguan (PC6) for 30 min each day for 4 consecutive days during HDBR). OT, plasma hormones, plasma volume and heart rate variability were assessed before and after HDBR. Cardiac function and cerebral blood flow were measured before, during and after HDBR.ResultsThe data showed that TEAS treatment mitigated the decrease in OT that was observed in the control group and cardiac function, alleviated autonomic dysfunction, and partially prevented plasma volume reduction after HDBR. Angiotensin II and aldosterone were significantly increased by 129.3% and 133.3% after HDBR in the TEAS group (p<0.05).ConclusionsThese results indicate that 30 min of daily TEAS treatment at PC6 is partially effective in maintaining OT, probably due to increased plasma volume-regulating hormones and activation of the peripheral sympathetic nervous system. TEAS treatment appears effective at reducing cardiovascular deconditioning induced by HDBR for 4 days.Trial registration numberNCT02300207.

Effects of 5 days of head-down bed rest, with and without short-arm centrifugation as countermeasure, on cardiac function in males (BR-AG1 study).

This study examined cardiac remodeling and functional changes induced by 5 days of head-down (-6°) bed rest (HDBR) and the effectiveness of short-arm centrifugation (SAC) in preventing them in males. Twelve healthy men (mean age: 33 ± 7) were enrolled in a crossover design study (BR-AG1, European Space Agency), including one sedentary (CTRL) and two daily SAC countermeasures (SAC1, 30 min continuously; SAC2, 30 min intermittently) groups. Measurements included plasma and blood volume and left ventricular (LV) and atrial (LA) dimensions by transthoracic echocardiography (2- and 3-dimensional) and Doppler inflows. Results showed that 5 days of HDBR had a major impact on both the geometry and cardiac function in males. LV mass and volume decreased by 16 and 14%, respectively; LA volume was reduced by 36%; Doppler flow and tissue Doppler velocities were reduced during early filling by 18 and 12%, respectively; and aortic flow velocity time integral was decreased by 18% with a 3% shortening of LV ejection time. These modifications were presumably due to decreased physiological loading and dehydration, resulting in reduced plasma and blood volume. All these changes were fully reversed 3 days after termination of HDBR. Moreover, SAC was not able to counteract these changes, either when applied continuously or intermittently.

Impaired T-wave amplitude adaptation to heart-rate induced by cardiac deconditioning after 5-days of head-down bed-rest

The study of QT/RR relationship is important for the clinical evaluation of possible risk of acquired or congenital ventricular tachyarrhythmias. In the hypothesis that microgravity exposure could induce changes in the repolarization mechanisms, our aim was to test if a short 5-days strict 6° head-down bed-rest (HDBR) could induce alterations in the QT/RR relationship and spatial repolarization heterogeneity. Twenty-two healthy men (mean age 31±6) were enrolled as part of the European Space Agency HDBR studies. High fidelity (1000Hz) 24h Holter ECG (12-leads, Mortara Instrument) was acquired before (PRE), the last day of HDBR (HDT5), and four days after its conclusion (POST). The night period (23:00–06:30) was selected for analysis. X, Y, Z leads were derived and the vectorcardiogram computed. Selective beat averaging was used to obtain averages of P–QRS–T complexes preceded by the same RR (10ms bin amplitude, in the range 900–1200ms). For each averaged waveform (i.e., one for each bin), T-wave maximum amplitude (Tmax), T-wave area (Tarea), RTapex, RTend, ventricular gradient (VG) magnitude and spatial QRS-T angle were computed. Non-parametric Friedman test was applied. Compared to PRE, at HDT5 both RTapex and RTend resulted shortened (−4%), with a decrease in T-wave amplitude (−8%) and area (−13%). VG was diminished by 10%, and QRS-T angle increased by 14°. At POST, QT duration and area parameters, as well as QRS-T angle were restored while Tmax resulted larger than PRE (+5%) and VG was still decreased by 3%. Also, a marked loss in strength of the linear regression with RR was found at HDT5 in Tmax and Tarea, that could represent a new dynamic marker of increased risk for life-threatening arrhythmias. Despite the short-term HDBR, ventricular repolarization during the night period was affected. This should be taken into account in astronauts for risk assessment during space flight.

Effects of simulated natural air movement on thermoregulatory response during head-down bed rest

Spaceflight and its bed rest analog impair thermoregulatory responses, including elevated core temperature observed at rest and during exercise. Natural air flow has been found to increase cold sensation significantly compared to artificial constant air flow (CAF). The present study tested the hypothesis that simulated natural air flow (SNAF) ventilation would ameliorate impaired thermoregulatory function to a greater extent than CAF under simulated microgravity conditions. Seven healthy males underwent 30 days of −6° head-down bed rest (HDBR). During pre-HDBR and the day 29 of HDBR (HDBR 29), the subjects were exposed to three air flow patterns at 23°C while in a supine posture: a still air flow control (CON), CAF, and SNAF. The mean air velocity of the latter two patterns was 0.2m/s. Subjective perception of the thermal environment was recorded by thermal sensation vote (TSV), and rectal temperature (Tre), skin temperature (Tsk), and cutaneous vascular conductance (CVC) were also measured during the sessions. Tre was significantly elevated after 29 days of HDBR and decreased to a greater extent in SNAF than in CAF on HDBR 29. However, there was no significant difference between Tre in SNAF on HDBR 29 and that in CON on pre-HDBR. Mean Tsk, CVC, and TSV in SNAF were also significantly lower than those in CAF on HDBR 29. Moreover, TSV was close to ‘neutral’ under SNAF on HDBR 29. These data indicate that simulated natural air movement might be more effective than constant air movement at preserving core temperature at a thermoneutral ambient temperature during HDBR.