Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion.

We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse.NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.

Dry immersion induced acute low back pain and its relationship with trunk myofascial viscoelastic changes.

Microgravity induces spinal elongation and Low Back Pain (LBP) but the pathophysiology is unknown. Changes in paraspinal muscle viscoelastic properties may play a role. Dry Immersion (DI) is a ground-based microgravity analogue that induces changes in m. erector spinae superficial myofascial tissue tone within 2 h. This study sought to determine whether bilateral m. erector spinae tone, creep, and stiffness persist beyond 2 h; and if such changes correlate with DI-induced spinal elongation and/or LBP. Ten healthy males lay in the DI bath at the Institute of Biomedical Problems (Moscow, Russia) for 6 h. Bilateral lumbar (L1, L4) and thoracic (T11, T9) trunk myofascial tone, stiffness and creep (MyotonPRO), and subjective LBP (0-10 NRS) were recorded before DI, after 1h, 6 h of DI, and 30min post. The non-standing spinal length was evaluated on the bath lifting platform using a bespoke stadiometer before and following DI. DI significantly modulated m. erector spinae viscoelastic properties at L4, L1, T11, and T9 with no effect of laterality. Bilateral tissue tone was significantly reduced after 1 and 6 h DI at L4, L1, T11, and T9 to a similar extent. Stiffness was also reduced by DI at 1 h but partially recovered at 6 h for L4, L1, and T11. Creep was increased by DI at 1 h, with partial recovery at 6 h, although only T11 was significant. All properties returned to baseline 30 min following DI. Significant spinal elongation (1.17 ± 0.20 cm) with mild (at 1 h) to moderate (at 6 h) LBP was induced, mainly in the upper lumbar and lower thoracic regions. Spinal length increases positively correlated (Rho = 0.847, p = 0.024) with middle thoracic (T9) tone reduction, but with no other stiffness or creep changes. Spinal length positively correlated (Rho = 0.557, p = 0.039) with Max LBP; LBP failed to correlate with any m. erector spinae measured parameters. The DI-induced bilateral m. erector spinae tone, creep, and stiffness changes persist beyond 2 h. Evidence of spinal elongation and LBP allows suggesting that the trunk myofascial tissue changes could play a role in LBP pathogenesis observed in real and simulated microgravity. Further study is warranted with longer duration DI, assessment of IVD geometry, and vertebral column stability.

Multiple field tests on landing day: Early mobility may improve postural recovery following spaceflight.

Adaptation to microgravity causes astronauts to experience sensorimotor disturbances during return to Earth leading to functional difficulties. Recently, the Field Test (FT) study involving an incrementally demanding sensorimotor functional test battery has allowed for an unprecedented view into early decrements and recovery from multiple tests conducted on the landing day following 6-months International Space Station missions. Although the protocol was challenging and temporarily increased motion sickness symptoms, there were anecdotal reports that performing these tasks within the first few hours of landing accelerated their recovery. Therefore, results from computerized dynamic posturography (CDP) following return to Houston were used to compare recovery between crewmembers that participated in FT (n = 18) with those that did not (controls, n = 11). While there were significant decrements in postural performance for both groups, some FT participants tended to perform closer to their preflight baseline in the most challenging condition of the CDP sensitive to vestibular function-eyes closed, unstable support and head movements. However, the distribution of difference scores appeared bimodal with other FT participants in the lower range of performance. We attribute these observations to the manner in which the field tests were implemented-some benefitted by encouraging early movement to drive adaptation when performed in a constrained incremental fashion; however, movements above aversive thresholds may have impaired adaptation in others. Challenging the sensorimotor system with increasingly provocative movements performed as close to landing as possible, as long as within individual thresholds, could be a useful intervention to accelerate astronaut's sensorimotor readaptation that deserves further study.

Application of Space Technologies Aimed at Proprioceptive Correction in Terrestrial Medicine in Russia.

Space technologies greatly contributed not only to space medicine but also to terrestrial medicine, which actively involves these technologies in everyday practice. Based on the existing countermeasures, and due to similarities of sensorimotor alterations provoked by the weightlessness with various neurological disorders, a lot of work has been dedicated to adaptation and introduction of these countermeasures for rehabilitation of patients. Axial loading suit and mechanical stimulation of the soles' support zones are used in mitigation of stroke and traumatic brain injury consequences. They are also applied for rehabilitation of children with cerebral palsy. Complex application of these proprioceptive correction methods in neurorehabilitation programs makes it possible to effectively treat neurological patients with severe motor disturbances and significant brain damage.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

Sharp Changes in Muscle Tone in Humans Under Simulated Microgravity.

A decrease in muscle tone induced by space flight requires a standardized assessment of changes to control the state of the neuromuscular system. This study is a step toward the development of a unified protocol, aimed at determining the initial effect of the presence or withdrawal of support on muscle tone, the effects of a 2-h supportlessness in Dry Immersion (DI) experiments, and the changes in muscle tone depending on the site of measurement. To perform measurements of changes in muscle tone, we used a MyotonPRO device. The list of muscles that we assessed includes: trunk - mm. deltoideus posterior, trapezius, erector spinae; leg - mm. biceps femoris, rectus femoris, tibialis anterior, soleus, gastrocnemius; foot - m. flexor digitorum brevis, tendo Achillis, aponeurosis plantaris. The study involved 12 healthy volunteers (6 men, 6 women) without musculoskeletal disorders and aged 32.8 ± 1.6 years. At the start of DI, there was a significant decrease in muscle tone of the following muscles: mm. tibialis anterior (-10.9%), soleus (-9.6%), erector spinae (-14.4%), and the tendo Achillis (-15.3%). The decrease continued to intensify over the next 2 h. In contrast, the gastrocnemius muscle demonstrated an increase in muscle tone (+7.5%) 2 h after the start of DI compared to the immediate in-bath baseline. Muscle tone values were found to be site-dependent and varied in different projections of mm. erector spinae and soleus. In previous experiments, we observed a high sensitivity of the myotonometry technique, which was confirmed in this study. To make it possible to compare data from different studies, a standardized protocol for measuring muscle tone for general use in gravitational physiology needs to be developed.

Efficacy of Gradient Compression Garments in the Hours After Long-Duration Spaceflight.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods: Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1-4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results: All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual's blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion: Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test.

Phase Coupling Between Baroreflex Oscillations of Blood Pressure and Heart Rate Changes in 21-Day Dry Immersion.

INTRODUCTION: Dry immersion (DI) is a ground-based experimental model which reproduces the effects of microgravity on the cardiovascular system and, therefore, can be used to study the mechanisms of post-flight orthostatic intolerance in cosmonauts. However, the effects of long-duration DI on cardiovascular system have not been studied yet. The aim of this work was to study the effects of 21-day DI on systemic hemodynamics and its baroreflex control at rest and during head-up tilt test (HUTT). METHODS: Ten healthy young men were exposed to DI for 21 days. The day before, on the 7th, 14th, and 19th day of DI, as well as on the 1st and 5th days of recovery they were subjected to HUTT: 15 min in supine position and then 15 min of orthostasis (60°). ECG, arterial pressure, stroke volume and respiration rate were continuously recorded during the test. Phase synchronization index (PSI) of beat-to-beat mean arterial pressure (MAP) and heart rate (HR) in the frequency band of baroreflex waves (∼0.1 Hz) was used as a quantitative measure of baroreflex activity. RESULTS: During DI, strong tachycardia and the reduction of stroke volume were observed both in supine position and during HUTT, these indicators did not recover on post-immersion day 5. In contrast, systolic arterial pressure and MAP decreased during HUTT on 14th day of DI, but then restored to pre-immersion values. Before DI and on day 5 of recovery, a transition from supine position to orthostasis was accompanied by an increase in PSI at the baroreflex frequency. However, PSI did not change in HUTT performed during DI and on post-immersion day 1. The amplitude of MAP oscillations at this frequency were increased by HUTT at all time points, while an increase of respective HR oscillations was absent during DI. CONCLUSION: 21-day DI drastically changed the hemodynamic response to HUTT, while its effect on blood pressure was reduced between days 14 and 19, which speaks in favor of the adaptation to the conditions of DI. The lack of increase in phase synchronization of baroreflex MAP and HR oscillations during HUTT indicates disorders of baroreflex cardiac control during DI.

Resting State Brain Activity During Long-Term Dry Immersion.

BACKGROUND: The purpose of this work was to investigate the brain's rhythmic activity during a simulated microgravity condition (namely dry immersion). METHODS: During dry immersion, which lasted for 5 d, nine subjects (healthy men, 20 to 29 yr of age) were individually placed in a tub (2.2 × 1.1 × 0.85 m) filled with water (temperature was kept constant at about 33°C). Subject floated in the tub without bodily support in the supine horizontal position, but isolated from the water by waterproof material. Resting state EEGs were registered at the fourth or fifth day of dry immersion. Under the control conditions, resting state EEGs were registered while subjects laid in a supine position on a couch. RESULTS: Compared to the control condition, EEG power in the alpha range (8-13 Hz) was greater in dry immersion; this effect was distributed across the whole scalp. No effects of dry immersion were found for the beta, delta, or theta frequency bands. CONCLUSION: The results of the study, similar to those obtained in a real spaceflight, indicate that support withdrawal is an important contributor to brain activity alterations in weightlessness.Lazarev IE, Tomilovskaya ES, Kozlovskaya IB. Resting state brain activity during long-term dry immersion. Aerosp Med Hum Perform. 2018; 89(7):642-647.

Effects of plantar stimulation on cardiovascular response to orthostatism.

PURPOSE: Walking is a complex locomotor process that involves both spinal cord reflexes and cortical integration of peripheral nerve input. Maintaining an upright body position requires not only neuromuscular activity but also cardiovascular regulation. We postulated that plantar mechanical stimulation might modulate autonomic nervous system activity and, thereby, impact blood pressure adaptation during standing. METHODS: Twelve healthy subjects underwent three randomly ordered 45-min 70°-saddle tilt tests while the plantar surfaces of the feet were stimulated using specially engineered Korvit boots in the following modes: (1) no stimulation, (2) disrupted stimulation, and (3) walking mode. Orthostatic tolerance time was measured for each trial. During testing, we obtained an electrocardiogram and measured blood pressure, skin blood flow, and popliteal vein cross-sectional area. We estimated central hemodynamics, baroreflex sensitivity and heart rate variability. RESULTS: Orthostatic tolerance time was not found to differ significantly between test conditions (37.2 ± 10.4, 40.9 ± 7.6, and 41.8 ± 8.2 min, for no stimulation, disrupted stimulation, and walking mode, respectively). No significant differences between treatment groups were observed for stroke volume or cardiac baroreflex sensitivity, both of which decreased significantly from baseline during tilt testing in all groups. Cardiac sympathetic index and popliteal vein cross-sectional area increased at the end of the tilt period in all groups, without significant differences between treatments. CONCLUSIONS: Plantar mechanical stimulation is insufficient for immediate modulation of cardiac sympathetic and parasympathetic activity under orthostatic stress.

Long-term dry immersion: review and prospects.

Dry immersion, which is a ground-based model of prolonged conditions of microgravity, is widely used in Russia but is less well known elsewhere. Dry immersion involves immersing the subject in thermoneutral water covered with an elastic waterproof fabric. As a result, the immersed subject, who is freely suspended in the water mass, remains dry. For a relatively short duration, the model can faithfully reproduce most physiological effects of actual microgravity, including centralization of body fluids, support unloading, and hypokinesia. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body (a phenomenon we call 'supportlessness'). In this review, we attempt to provide a detailed description of dry immersion. The main sections of the paper discuss the changes induced by long-term dry immersion in the neuromuscular and sensorimotor systems, fluid-electrolyte regulation, the cardiovascular system, metabolism, blood and immunity, respiration, and thermoregulation. The long-term effects of dry immersion are compared with those of bed rest and actual space flight. The actual and potential uses of dry immersion are discussed in the context of fundamental studies and applications for medical support during space flight and terrestrial health care.