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After longer duration space missions, some astronauts experience structural and functional changes in the eye and structural changes in the brain, termed Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Countermeasures against SANS are required to minimize potential operation impacts and negative long-term health consequences. Headward fluid shifts, which appear to promote SANS, provide a target for countermeasures. The SANS countermeasures study, a 30 days strict head down tilt bed rest (HDTBR) study, tested two mechanical countermeasures aimed at reversing cephalad fluid overload. This work presents design and methodology of the study with a focus on countermeasure implementation and tolerability. Following baseline evaluations, participants were randomized to four groups and HDTBR commenced: Daily application of 25 mmHg lower body negative pressure for 6 h, six-hour bilateral venous constrictive thigh cuffs following moderate cycling exercise on 6 days per week, a negative control group without countermeasures, and a positive control group with HDTBR interruption for 6 h per day by sitting upright. The potential of these countermeasures for future space applications was examined in 86 different experiments, which will be reported elsewhere. Comfort ratings ranging from 1 (very uncomfortable) to 5 (very comfortable) were used to asses tolerability. Overall, 47 participants (20 women) completed the study. Out of 4,032 h scheduled for both countermeasures, 10.5 h were not performed due to medical issues unrelated to the countermeasures. Mean comfort ratings were 3.9 in men and 4.4 in women in the lower body negative pressure group (p = 0.1356) and 4.2 in men and 3.9 in women in the thigh cuff group (p = 0.1604). We conclude that both countermeasures were well tolerated and applied under well controlled conditions, thus, allowing for meaningful analyses of efficacy in attenuating HDTBR effects.

BackgroundChanges in blood vessel properties have been identified with confinement, spaceflight, bedrest, and dry immersion. Subsequently, it was suspected that other organs may also be affected in these extreme environments. The purposes of the current study were to determine the effects of head-down bedrest (HDT) on cardiovascular and organ measurements made using ultrasound imaging similar to that currently available on the International Space Station, and to evaluate the efficacy of two different countermeasure protocols in preventing any observed changes in the ultrasound measurements with HDT.MethodsUltrasound measures were conducted on 24 individuals (3 groups of 8) pre HDT and on day 55 of the HDT. The control group (C°) remained in passive HDT for the 55 days, the C1 group performed aerobic exercise daily (EX), and the C2 group practiced aerobic exercise under artificial gravity conditions (EX-AG). Fifteen parameters were measured on 10 different organs and blood vessels including the right common carotid artery, abdominal aorta, right tibial artery, left ventricle, right jugular vein, portal vein, right kidney, cervical and lumbar vertebra, and the vastus intermedius muscle.ResultsHDT resulted in changes for many of the parameters investigated. Observed changes in carotid IMT and distensibility, cardiac ejection fraction, portal vein diameter, and vastus intermedius muscle thickness were attenuated with EX and EX-AG, with EX-AG having a greater effect than exercise alone on measures of carotid distensibility.ConclusionResults from this study indicate changes in many structures assessed with ultrasound imaging after 55 days of HDT bedrest with some changes being attenuated with the two investigated countermeasure protocols.

Abstract Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head‐down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14‐day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55–65 underwent baseline measurements, 14 days of −6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well‐being and aiding bedrest‐bound older adults. By outlining evidence‐based interventions, this research supports both space travellers and those enduring prolonged bedrest.

Significant progress has been made in the development of countermeasures to attenuate the negative consequences of prolonged exposure to microgravity on astronauts’ bodies. Deconditioning of several organ systems during flight includes losses to cardiorespiratory fitness, muscle mass, bone density and strength. Similar deconditioning also occurs during prolonged bedrest; any protracted time immobile or inactive, especially for unwell older adults (e.g., confined to hospital beds), can lead to similar detrimental health consequences. Due to limitations in physiological research in space, the six-degree head-down tilt bedrest protocol was developed as ground-based analogue to spaceflight. A variety of exercise countermeasures have been tested as interventions to limit detrimental changes and physiological deconditioning of the musculoskeletal and cardiovascular systems. The Canadian Institutes of Health Research and the Canadian Space Agency recently provided funding for research focused on Understanding the Health Impact of Inactivity to study the efficacy of exercise countermeasures in a 14-day randomized clinical trial of six-degree head-down tilt bedrest study in older adults aged 55–65 years old (BROA). Here we will describe the development of a multi-modality countermeasure protocol for the BROA campaign that includes upper- and lower-body resistance exercise and head-down tilt cycle ergometry (high-intensity interval and continuous aerobic exercise training). We provide reasoning for the choice of these modalities following review of the latest available information on exercise as a countermeasure for inactivity and spaceflight-related deconditioning. In summary, this paper sets out to review up-to-date exercise countermeasure research from spaceflight and head-down bedrest studies, whilst providing support for the proposed research countermeasure protocols developed for the bedrest study in older adults.

Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.

Atrophy, bedrest, calcium, disuse, neuromuscular junction, sarcopenia, skeletal muscle, unloading Keywords: atrophy; bedrest; calcium; disuse; neuromuscular junction; sarcopenia; skeletal muscle; unloading EN atrophy bedrest calcium disuse neuromuscular junction sarcopenia skeletal muscle unloading 4249 4251 3 09/16/21 20210915 NES 210915 Maintaining skeletal muscle mass is essential for normal ambulatory function and metabolism. These data, together with altered expression of genes related to NMJ (e.g. AGRN, CHRNA1 and HOMER2), suggest that just 10 days of bedrest may be sufficient to result in a loss of NMJ stability. [Extracted from the article]

This paper provides a general overview of key physiological consequences of microgravity experienced during spaceflight and of important parallels and connections to the physiology of aging. Microgravity during spaceflight influences cardiovascular function, cerebral autoregulation, musculoskeletal, and sensorimotor system performance. A great deal of research has been carried out to understand these influences and to provide countermeasures to reduce the observed negative consequences of microgravity on physiological function. Such research can inform and be informed by research related to physiological changes and the deterioration of physiological function due to aging. For example, head-down bedrest is used as a model to study effects of spaceflight deconditioning due to reduced gravity. As hospitalized older persons spend up to 80% of their time in bed, the deconditioning effects of bedrest confinement on physiological functions and parallels with spaceflight deconditioning can be exploited to understand and combat both variations of deconditioning. Deconditioning due to bed confinement in older persons can contribute to a downward spiral of increasing frailty, orthostatic intolerance, falls, and fall-related injury. As astronauts in space spend substantial amounts of time carrying out exercise training to counteract the microgravity-induced deconditioning and to counteract orthostatic intolerance on return to Earth, it is logical to suggest some of these interventions for bed-confined older persons. Synthesizing knowledge regarding deconditioning due to reduced gravitational stress in space and deconditioning during bed confinement allows for a more comprehensive approach that can incorporate aspects such as (mal-) nutrition, muscle strength and function, cardiovascular (de-) conditioning, and cardio-postural interactions. The impact of such integration can provide new insights and lead to methods of value for both space medicine and geriatrics (Geriatrics meets spaceflight!). In particular, such integration can lead to procedures that address the morbidity and the mortality associated with bedrest immobilization and in the rising health care costs associated with an aging population demographic.

Purpose: The objective was to determine the separate and combined effects of hypoxia and inactivity/unloading on sleep architecture during a 10-day period of confinement. Methods: Ten subjects participated in three 10-day trials in random order: hypoxic ambulatory (HAMB), hypoxic bedrest (HBR), and normoxic bedrest (NBR). During the HAMB and HBR trials, subjects were confined to a hypoxic facility. The hypoxia profile was: simulated altitude of 2,990 m on day 1, 3,380 m on day 2, and 3,881 m on day 3. In the NBR and HBR trials, subjects maintained a horizontal position throughout the confinement period. During each trial, sleep polysomnography was conducted one night prior to (baseline; altitude of facility is 940 m) and on the first (NT1, altitude 2,990 m) and tenth (NT10, altitude 3,881 m) night of the 10-day intervention. Results: Average time in sleep stage 1 decreased from NT1 to NT10 irrespective of trial. Overall incidence and time spent in periodic breathing increased from NT1 to NT10 in both HAMB and HBR. During NT1, both HAMB and HBR reduced slow-wave sleep and increased light sleep, whereas NBR and HBR increased the number of awakenings/night. There were fewer awakenings during HAMB than NBR. Conclusions: Acute exposure to both hypoxia and bedrest (HBR) results in greater sleep fragmentation due to more awakenings attributed to bedrest, and lighter sleep as a result of reduced slow wave sleep caused by the hypoxic environment. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the time course of maximal oxygen consumption (...O2max) changes during bedrests longer than 30 days, on the hypothesis that the decrease in ...O2max tends to asymptote. On a total of 26 subjects who participated in one of three bedrest campaigns without countermeasures, lasting 14, 42 and 90 days, respectively, ...O2max maximal cardiac output (...max) and maximal systemic O2 delivery (...aO2max) were measured. After all periods of HDT, ...O2max ...max and ...aO2max were significantly lower than before. The ...O2max decreased less than Qmax after the two shortest bedrests, but its per cent decay was about 10% larger than that of ...max after 90-day bedrest. The ...O2max decrease after 90-day bedrest was larger than after 42- and 14-day bedrests, where it was similar. The ...max and ...aO2 declines after 90-day bedrest was equal to those after 14- and 42-day bedrest. The average daily rates of the ...O2max, ...max and ...aO2max decay during bedrest were less if the bedrest duration were longer, with the exception of that of...O2max in the longest bedrest. The asymptotic ...O2max decay demonstrates the possibility that humans could keep working effectively even after an extremely long time in microgravity. Two components in the ...O2max decrease were identified, which we postulate were related to cardiovascular deconditioning and to impairment of peripheral gas exchanges due to a possible muscle function deterioration. [ABSTRACT FROM AUTHOR]

To examine the effects of unweighting on the structural and metabolic adaptations of a non-postural muscle, deltoideus muscle biopsies were taken in seven male healthy subjects, before and after a 37 day bedrest. Myofibrillar ATPase histochemistry demonstrated no change in fibre type distributions (I, IIA, IIB), in fibre cross-sectional areas nor in capillary supply. No difference was noted in enzyme activities of oxidative metabolism (citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase), and glycolysis (hexokinase, lactate dehydrogenase). Electron microscopy showed a decrease in the volume density of lipids but no change in mitochondrial volume density and distribution. The results indicate that bedrest induces no major morphological and biochemical changes in deltoideus muscle, contrary to what was previously reported in vastus lateralis muscle. This lack of changes is probably related to an unaltered deltoideus muscle use. [ABSTRACT FROM AUTHOR]