Days Of Bed Rest Research Articles

THE EFFECT OF SHORT DURATION BED REST AND TYPE 2 DIABETES MELLITUS ON ARTERIAL STRUCTURE AND FUNCTION IN OLDER ADULTS

Abstract Type 2 diabetes mellitus (T2DM) and inactivity individually accelerate changes related to vascular aging. These changes increase cardiovascular risk and contribute to morbidity and mortality in the elderly. It is unknown if T2DM and bed rest have an additive, deleterious effect on vascular structure and function in older adults. The objective of this study is to determine the magnitude of the effect of bed rest on vascular structure in older adults with T2DM compared to healthy controls and determine if resistance exercise is protective of this effect. So far, we have recruited T2DM (n=9) and healthy control (n=17) subjects (age: 67.0 ± 6.7 years) to undergo five days of bed rest. During bed rest, subjects were randomized to receive intensive bedside resistance exercise physical therapy or standard of care in-bed passive physical therapy. On bed rest days 1 and 5, popliteal artery diameter, area, blood velocity, and blood flow were measured using Doppler ultrasonography. Our preliminary data show that the T2DM, non-exercise group had significantly greater decreases in popliteal artery diameter (-0.59 mm ± 0.18) than the control, non-exercise group (-0.17 mm ± 0.11). Resistance exercise did not prevent artery size changes in either controls or T2DM. Resistance exercise showed a trend in preventing blood velocity and flow reduction in both T2DM and control groups. These preliminary data suggest that older adults with T2DM had greater structural popliteal artery changes compared to controls. Resistance exercise appears to help maintain blood flow by maintaining/increasing popliteal artery blood velocity, but not size.

DAILY EXERCISE DOES NOT ALTER CEREBRAL BLOOD FLOW REGULATION DURING TILT IN OLDER ADULTS AFTER TWO WEEKS OF BEDREST

Abstract Bedrest is associated with cardiovascular and cerebrovascular changes that are linked to a greater prevalence of orthostatic intolerance; however, much of what we know from bedrest trials comes from young adults. How older adults respond to extended periods of activity restriction is not well understood. The current work tested the hypothesis that impaired control of cerebral blood flow in older adults following bedrest could be attenuated by regular exercise. Twenty-two older adults (55-65 years, 11 women) participated in a randomized controlled trial involving 14 days of continuous 6-degree head-down bedrest. The cohort was randomized to an exercise intervention (EX), involving daily aerobic, high-intensity interval, and resistance training, or a control group (CON), involving passive manual therapy. Cerebral blood flow velocity, cardiac output, and arterial blood pressure were measured continuously during a passive 80-degree head-up tilt protocol for up to 15 minutes. Responses in the cerebral and peripheral vascular beds were quantified by vascular resistance (cerebral: resistance area product (RAP); peripheral: total peripheral resistance (TPR)). Following bedrest, both supine RAP and TPR were elevated (p< 0.01), with no effect of exercise training. In addition, the number of participants who could not complete 15 minutes of tilt increased from 3 to 15 (8 EX, 7 CON). In these non-finishers, RAP dropped ~20% and TPR dropped ~15% during the final 2 minutes of tilt, with no difference between groups. These data suggest that multimodal exercise training is insufficient to prevent changes in cardiovascular and cerebrovascular regulation in older adults observed during 14-day bedrest.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P=0.02) and decreased to 0.6-fold the initial abundance after 2days of recovery at normal daily activity (R+2, 2.7E9, P=3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P=1.5E-4) at BR10 and remained as low at R+2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P=0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

The Characteristic Response of the Human Leukocyte Transcriptome to 60 Days of Bed Rest and to Reambulation.

We sought to isolate the microgravity effect of spaceflight from other space stressors by characterizing the leukocytes' transcriptome of participants to a 60-d bed rest study; an Earth model of microgravity. Twenty healthy men received a nutritional supplement or not and 10 blood samples were collected throughout three study phases: baseline data collection (BDC) (BDC-12, BDC-11), head-down tilt (HDT) bed rest (HDT1, HDT2, HDT30, HDT60), and reambulation (R1, R2, R12, R30). We measured gene expression through RNA sequencing of leukocytes, applied generalized linear models to assess differential expression followed by enrichment analysis to identify temporal changes (model 1) and to measure the impact of a nutritional supplement (model 2). Baseline transcriptomes included 14,624 protein-coding transcripts and showed both high intraindividual correlations (mean Kendall coefficient, 0.91 ± 0.04) and interindividual homogeneity (0.89 ± 0.03). We identified 2415 differentially expressed protein-coding transcripts grouping into six clusters (C1-C6). At phase transitions, clusters showed either a decrease-then-increase (C3 and C5) or an increase-then-decrease (C1, C2, C6) pattern. All six clusters converged toward average expression at HDT30 and HDT60. Gene ontology terms at baseline related to immune functions while in bed rest and reambulation related to sequestration of ions, immune response, cellular stress, and mineralization. The nutritional intervention had no effect. The temporal profiles of leukocytes' transcriptomes emphasized the dynamic nature of gene expression occurring during and after bed rest. Enriched biological processes among the differentially expressed genes included immune related and unrelated responses. The convergence toward no differential expression at days 30 and 60 of bed rest suggests a hypometabolic state. Current findings can guide future work on the complex responses and adaptation mechanisms to microgravity.

Cardiovascular deconditioning and impact of artificial gravity during 60-day head-down bed rest-Insights from 4D flow cardiac MRI.

Microgravity has deleterious effects on the cardiovascular system. We evaluated some parameters of blood flow and vascular stiffness during 60 days of simulated microgravity in head-down tilt (HDT) bed rest. We also tested the hypothesis that daily exposure to 30 min of artificial gravity (1 g) would mitigate these adaptations. 24 healthy subjects (8 women) were evenly distributed in three groups: continuous artificial gravity, intermittent artificial gravity, or control. 4D flow cardiac MRI was acquired in horizontal position before (−9 days), during (5, 21, and 56 days), and after (+4 days) the HDT period. The false discovery rate was set at 0.05. The results are presented as median (first quartile; third quartile). No group or group × time differences were observed so the groups were combined. At the end of the HDT phase, we reported a decrease in the stroke volume allocated to the lower body (−30% [−35%; −22%]) and the upper body (−20% [−30%; +11%]), but in different proportions, reflected by an increased share of blood flow towards the upper body. The aortic pulse wave velocity increased (+16% [+9%; +25%]), and so did other markers of arterial stiffness (; ). In males, the time-averaged wall shear stress decreased (−13% [−17%; −5%]) and the relative residence time increased (+14% [+5%; +21%]), while these changes were not observed among females. Most of these parameters tended to or returned to baseline after 4 days of recovery. The effects of the artificial gravity countermeasure were not visible. We recommend increasing the load factor, the time of exposure, or combining it with physical exercise. The changes in blood flow confirmed the different adaptations occurring in the upper and lower body, with a larger share of blood volume dedicated to the upper body during (simulated) microgravity. The aorta appeared stiffer during the HDT phase, however all the changes remained subclinical and probably the sole consequence of reversible functional changes caused by reduced blood flow. Interestingly, some wall shear stress markers were more stable in females than in males. No permanent cardiovascular adaptations following 60 days of HDT bed rest were observed.

Capillary rarefaction during bed rest is proportionally less than fibre atrophy and loss of oxidative capacity.

Muscle disuse from bed rest or spaceflight results in losses in muscle mass, strength and oxidative capacity. Capillary rarefaction may contribute to muscle atrophy and the reduction in oxidative capacity during bed rest. Artificial gravity may attenuate the negative effects of long-term space missions or bed rest. The aim of the present study was to assess (1) the effects of bed rest on muscle fibre size, fibre type composition, capillarization and oxidative capacity in the vastus lateralis and soleus muscles after 6 and 55days of bed rest and (2) the effectiveness of artificial gravity in mitigating bed-rest-induced detriments to these parameters. Nineteen participants were assigned to a control group (control, n=6) or an intervention group undergoing 30min of centrifugation (n=13). All underwent 55days of head-down tilt bed rest. Vastus lateralis and soleus biopsies were taken at baseline and after 6 and 55days of bed rest. Fibre type composition, fibre cross-sectional area, capillarization indices and oxidative capacity were determined. After just 6days of bed rest, fibre atrophy (-23.2±12.4%, P<0.001) and reductions in capillary-to-fibre ratio (C:F; 1.97±0.57 vs. 1.56±0.41, P<0.001) were proportional in both muscles as reflected by a maintained capillary density. Fibre atrophy proceeded at a much slower rate between 6 and 55days of bed rest (-11.6±12.1% of 6days, P=0.032) and was accompanied by a 19.1% reduction in succinate dehydrogenase stain optical density (P<0.001), without any further significant decrements in C:F (1.56±0.41 vs. 1.49±0.37, P=0.459). Consequently, after 55days of bed rest, the capillary supply-oxidative capacity ratio of a fibre had increased by 41.9% (P<0.001), indicating a capillarization in relative excess of oxidative capacity. Even though the heterogeneity of capillary spacing (LogR SD) was increased after 55days by 12.7% (P=0.004), tissue oxygenation at maximal oxygen consumption of the fibres was improved after 55days bed rest. Daily centrifugation failed to blunt the bed-rest-induced reductions in fibre size and oxidative capacity and capillary rarefaction. The relationship between fibre size and oxidative capacity with the capillary supply of a fibre is uncoupled during prolonged bed rest as reflected by a rapid loss of muscle mass and capillaries, followed at later stages by a more than proportional loss of mitochondria without further capillary loss. The resulting excessive capillary supply of the muscle after prolonged bed rest is advantageous for the delivery of substrates needed for subsequent muscle recovery.

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.

International standard measures during the AGBRESA bed rest study

The Artificial Gravity Bed Rest with European Space Agency (AGBRESA) study involved 2 campaigns of 60-day bed rest at 6° head down tilt in the:envihab facility in Cologne, Germany, in 2019. The objective was to determine whether centrifugation of supine subjects mitigates physiological changes that occur due to the exposure to the spaceflight analog of 6° head down tilt. A set of international standard measures was used to evaluate bone, muscle, nutritional status, ocular changes, and psychological state and to assess cardiovascular, sensorimotor, and immune systems functions. After 60 days of bed rest, the subjects who were not exposed to centrifugation had significant decreases in mineral density at the hip and lumbar spine, decreased muscle strength of the knee and ankle, reduced maximal aerobic capacity, orthostatic intolerance, and impaired balance and locomotion, as well as significant biochemical, immunological, and psychological alterations. A daily 30-min exposure to 1 Gz supine centrifugation at the center of mass (0.3 Gz at the head, 2 Gz at the feet) mitigated mineral density loss in the femur neck and lumbar spine; and lessened the effects of bed rest on aerobic capacity, biochemistry, and immunology. However, low statistical power could contribute to the non-significant effects that are reported.

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.

Mechanical deconditioning of the heart due to long-term bed rest as observed on seismocardiogram morphology

During head-down tilt bed rest (HDT) the cardiovascular system is subject to headward fluid shifts. The fluid shift phenomenon is analogous to weightlessness experienced during spaceflight microgravity. The purpose of this study was to investigate the effect of prolonged 60-day bed rest on the mechanical performance of the heart using the morphology of seismocardiography (SCG). Three-lead electrocardiogram (ECG), SCG and blood pressure recordings were collected simultaneously from 20 males in a 60-day HDT study (MEDES, Toulouse, France). The study was divided into two campaigns of ten participants. The first commenced in January, and the second in September. Signals were recorded in the supine position during the baseline data collection (BDC) before bed rest, during 6° HDT bed rest and during recovery (R), post-bed rest. Using SCG and blood pressure at the finger, the following were determined: Pulse Transit Time (PTT); and left-ventricular ejection time (LVET). SCG morphology was analyzed using functional data analysis (FDA). The coefficients of the model were estimated over 20 cycles of SCG recordings of BDC12 and HDT52. SCG fiducial morphology AO (aortic valve opening) and AC (aortic valve closing) amplitudes showed significant decrease between BDC12 and HDT52 (p < 0.03). PTT and LVET were also found to decrease through HDT bed rest (p < 0.01). Furthermore, PTT and LVET magnitude of response to bed rest was found to be different between campaigns (p < 0.001) possibly due to seasonal effects on of the cardiovascular system. Correlations between FDA and cardiac timing intervals PTT and LVET using SCG suggests decreases in mechanical strength of the heart and increased arterial stiffness due to fluid shifts associated with the prolonged bed rest.

No effect of five days of bed rest or short-term resistance exercise prehabilitation on markers of skeletal muscle mitochondrial content and dynamics in older adults.

Bed rest (BR) results in significant impairments in skeletal muscle metabolism. Mitochondrial metabolism is reportedly highly sensitive to disuse, with dysregulated fission‐fusion events and impaired oxidative function previously reported. The effects of clinically relevant short‐term BR (≤5 days) on mitochondrial protein expression are presently unclear, as are the effects of exercise prehabilitation as a potential counteractive intervention. The present study examined the effects of a 5‐day period of BR and short‐term resistance exercise prehabilitation (ST‐REP) on mitochondrial‐protein content. Ten older men (71 ± 4 years) underwent 5 days of BR, completing four sessions of high‐volume unilateral resistance exercise prehabilitation over 7 days beforehand. Muscle biopsies were obtained from the vastus lateralis in the non‐exercised control and exercised legs, both pre‐ and post‐prehabilitation and pre‐ and post‐BR, to determine changes in citrate synthase enzyme activity and the expression of key proteins in the mitochondrial electron transport chain and molecular regulators of fission‐fusion dynamics, biosynthesis, and mitophagy. We observed no significant effect of either BR or ST‐REP on citrate synthase protein content, enzyme activity, or ETC complex I‐V protein content. Moreover, we observed no significant changes in markers of mitochondrial fission and fusion (p‐DRP1S616, p‐DRP1S637, p‐DRP1S616/S637 ratio, p‐MFFS146, Mitofillin, OPA1, or MFN2 (p > 0.05 for all). Finally, we observed no differences in markers of biosynthesis (p‐AMPKT172, p‐ACCS79, PGC1a, TFAM) or mitophagy‐related signaling (ULK‐1, BNIP3/NIX, LC3B I/II) (p > 0.05 for all). In contrast to previous longer‐term periods of musculoskeletal disuse (i.e., 7–14 days), a clinically relevant, 5‐day period of BR resulted in no significant perturbation in muscle mitochondrial protein signaling in healthy older adults, with no effect of ST‐REP in the week prior to BR. Accordingly, disuse‐induced muscle atrophy may precede alterations in mitochondrial content.

Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk.

Simple SummaryIrisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity.The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.

The Effects of Reconditioning Exercises Following Prolonged Bed Rest on Lumbopelvic Muscle Volume and Accumulation of Paraspinal Muscle Fat

Reduced muscle size and accumulation of paraspinal muscle fat content (PFC) have been reported in lumbopelvic muscles after spaceflights and head-down tilt (HDT) bed rest. While some information is available regarding reconditioning programs on muscle atrophy recovery, the effects on the accumulation of PFC are unknown. Recently, a device (the Functional Re-adaptive Exercise Device—FRED) has been developed which aims to specifically recruit lumbopelvic muscles. This study aimed to investigate the effects of a standard reconditioning (SR) program and SR program supplemented by FRED (SR + FRED) on the recovery of the lumbopelvic muscles following 60-day HDT bed rest. Twenty-four healthy participants arrived at the facility for baseline data collection (BDC) before the bed rest period. They remained in the facility for 13-day post-HDT bed rest and were randomly allocated to one of two reconditioning programs: SR or SR + FRED. Muscle volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles were measured from axial T1-weighted magnetic resonance imaging (MRI) at all lumbar intervertebral disc levels. PFC was determined using a chemical shift-based lipid/water Dixon sequence. Each lumbopelvic muscle was segmented into four equal quartiles (from medial to lateral). MRI of the lumbopelvic region was conducted at BDC, Day-59 of bed rest (HDT59), and Day-13 after reconditioning (R13). Comparing R13 with BDC, the volumes of the LM muscle at L4/L5 and L5/S1, LES at L1/L2, and QL at L3/L4 had not recovered (all—p < 0.05), and the PM muscle remained larger at L1/L2 (p = 0.001). Accumulation of PFC in the LM muscle at the L4/L5 and L5/S1 levels remained higher in the centro-medial regions at R13 than BDC (all—p < 0.05). There was no difference between the two reconditioning programs. A 2-week reconditioning program was insufficient to fully restore all volumes of lumbopelvic muscles and reverse the accumulation of PFC in the muscles measured to BDC values, particularly in the LM muscle at the lower lumbar levels. These findings suggest that more extended reconditioning programs or alternative exercises may be necessary to fully restore the size and properties of the lumbopelvic muscles after prolonged bed rest.

Blood Flow Restriction Training-An Overview and Implication in New Generation Physical Therapy: A Narrative Review.

Blood Flow Restriction Training (BFRT) is a novel strengthening technique utilitarian in many conditions. But there is lack of exploration on this clinical intervention. The training can prove to be a boon in many conditions such as muscle weakness, degenerative among others. It can serve to be an essential treatment in prevention of disuse atrophy occurring on the initial days of bed-rest on post surgical patients and improve circulation. BFRT with aerobic activities can improve cardiovascular fitness and holistically help in rehabilitation. The electronic databases such as PubMed, ScienceDirect, Scopus and Google Scholars were reviewed including the reference lists to retrieve relevant information regarding the topic. The result of the review states that BFRT is a novel strength training program that has not been explored in India but is very effective, less expensive and innovative way of rehabilitation. The utility of BFRT is evident in post-operative disuse atrophy in the initial days of bed-rest. The evidence depict that BFRT is a very effective training modality that can efficiently improve the muscle function, strength and mass.

Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest.

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.

Inter-Person Differences in Isometric Coactivations of Triceps Surae and Tibialis Anterior Decrease in Young, but Not in Older Adults After 14 Days of Bed Rest

We examined activation patterns of the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), soleus (SO), and tibialis anterior (TA) muscles in eight older (58.4 ± 3.3 years) and seven young (23.1 ± 2.9 years) participants, before and after 14 days of horizontal bed rest. Visual feedback on the exerted muscle torque was provided to the participants. The discharge patterns of individual motor units (MUs) were studied in three repetitions of isometric plantar flexion at 30 and 60% of Maximum Voluntary Contraction (MVC), before, and 1 day after the 14-day bed rest, respectively. In the GL and GM muscles, the older participants demonstrated higher MU discharge rates than the young, regardless of the contraction level, both before and after the bed rest. In the TA and SO muscles, the differences between the older and young participants were less consistent. Detailed analysis revealed person-specific changes in the MU discharge rates after the bed rest. To quantify the coactivation patterns we calculated the correlation coefficients between the cumulative spike trains of identified MUs from each muscle, and measured the root mean square difference of the correlation coefficients between the trials of the same session (intra-session variability) and between different sessions (inter-session variability) in each participant (intra-person comparison) and across participants (inter-person comparison). In the intra-person comparison, the inter-session variability was higher than the intra-session variability, either before or after the bed rest. At 60% MVC torque, the young demonstrated higher inter-person variability of coactivation than the older participants, but this variability decreased significantly after the bed rest. In older participants, inter-person variability was consistently lower at 60% than at 30% MVC torque. In young participants, inter-person variability became lower at 60% than at 30% MVC torque only after the bed rest. Precaution is required when analyzing the MU discharge and coactivation patterns, as individual persons demonstrate individual adaptations to aging or bed rest.

A comparison between left ventricular ejection time measurement methods during physiological changes induced by simulated microgravity.

New Findings What is the central question of this study? First, we validated easy‐to‐use oscillometric left ventricular ejection time (LVET) against echocardiographic LVET. Second, we investigated progression of left ventricular ejection time index (LVETI), pre‐ejection period index (PEPI), total electromechanical systole index (QS2I) and PEP/LVET ratio during 60 days of head‐down tilt (HDT). What is the main finding and its importance? The LVETosci and LVETecho showed good agreement in effect direction. Hence, LVETosci might be useful to evaluate cardiovascular responses during space flight. Moreover, the approach might be useful for individual follow‐up of patients with altered ejection times. Furthermore, significant effects of 60 days of HDT were captured by measurements of LVETI, PEPI, QS2I and PEP/LVET ratio. Systolic time intervals that are easy to detect might be used as parameters reflecting cardiovascular deconditioning. We compared left ventricular ejection time (LVET) measured via ultrasound Doppler on the left ventricular outflow tract with oscillometrically measured LVET, measured at the brachialis. Furthermore, we assessed the progression of the left ventricular ejection time index (LVETI), the pre‐ejection period index (PEPI), the Weissler index (PEP/LVET) and the total electromechanical systole index (QS2I) during prolonged strict head‐down tilt (HDT) bed rest, including 16 male and eight female subjects. Simultaneous oscillometric and echocardiographic LVET measurements showed significant correlation (r = 0.53 with P = 0.0084 before bed rest and r = 0.73 with P < 0.05 on the last day of bed rest). The shortening of LVET during HDT bed rest measured with both approaches was highly concordant in their effect direction, with a concordance rate of 0.96. Our results also demonstrated a significant decrease of LVETI (P < 0.0001) and QS2I (P = 0.0992) and a prolongation of PEPI (P = 0.0049) and PEP/LVET (P = 0.0003) during HDT bed rest over 60 days. Four days after bed rest, LVETI recovered completely to its baseline value. Owing to the relationship between shortening of LVETI and heart failure progression, the easy‐to‐use oscillometric method might not only be a useful way to evaluate the cardiovascular system during space flights, but could also be of high value in a clinical setting.

The impact of ABCDE bundle implementation on patient outcomes: A nationwide cohort study.

The ABCDE bundle is a set of evidence-based practices to systematically reduce the risks of sedation, delirium, and immobility in intensive care patients. Implementing the bundle improves clinical outcome. To investigate the association between patient outcomes and compliance with bundle components ABC (analgosedation algorithms), D (delirium protocol), and E (early mobilization protocol). A Spanish multicentre cohort study of adult patients receiving invasive mechanical ventilation (IMV) for ≥48 h until extubation. The primary outcome was pain level, cooperation to permit Medical Research Council Scale administration, patient days of delirium, and mobility. The secondary outcome was cumulative drug dosing by IMV days. Tertiary outcomes (ICU days, IMV days, bed rest days, ICU mortality, ICUAW) and independent variables (analgosedation, delirium, early mobilization protocols) were also studied. Data were collected from 605 patients in 80 ICUs and 5214 patient days with IMV. Two-thirds of the ICUs studied applied no protocols. Pain was not assessed on 83.6% of patient days. Patient cooperation made scale administration feasible on 20.7% of days. Delirium and immobility were found on 4.2% and 69.9% of days, respectively. Patients had shorter stays in ICUs with bundle protocols and fewer days of IMV in ICUs with delirium and mobilization bundle components (P=0.006 and P=0.03, respectively). Analgosedation protocols were associated with more opioid dosing (P=0.02), and delirium and early mobilization protocols with more propofol (P=0.001), dexmedetomidine (P=0.001), and lower benzodiazepine dosing (P=0.008). The implementation rate of ABCDE bundle components was very low in our Spanish setting, but when implemented, patients had a shorter ICU stay, more analgesia dosing, and lighter sedation. Applying some but not all the bundle components, there is increased analgesia and light sedation drug use, decreased benzodiazepines, and increased patient cooperation and mobility, resulting in a shorter ICU stay and fewer days of IMV.

Effect of Nightly Lower Body Negative Pressure on Choroid Engorgement in a Model of Spaceflight-Associated Neuro-ocular Syndrome

Astronauts returning from long-duration spaceflight experience ocular remodeling related to cephalad fluid shifts induced by microgravity. It is hypothesized that the absence of diurnal reductions in intracranial pressure in microgravity creates a low but persistent pressure gradient at the posterior aspect of the eye, which results in ocular remodeling and space-associated neuro-ocular syndrome (SANS) over many months. To determine whether partial reintroduction of footward fluid shifts during simulated microgravity via lower body negative pressure (LBNP) during sleep attenuates choroid engorgement, an early marker of ocular remodeling related to SANS. Between May 2019 and February 2020, participants with no major cardiovascular, kidney, or ophthalmic disease completed 3 days of supine (0°) bed rest with and 3 days without 8 hours of nightly LBNP in a randomized, crossover design. This single-center investigation took place at the UT Southwestern Medical Center. All analyses were conducted blinded to condition and time point. Eight hours of nightly LBNP (-20 mm Hg) vs no LBNP. The primary outcome was the change in choroid area and volume after 3 days of bed rest measured by optical coherence tomography. Of 10 participants, 5 were female, the mean (SD) age was 29 (9) years, and the age range was 18 to 55 years. Central venous pressure increased from the seated to supine position (mean [SD], seated: -2.3 [2.0] vs supine: 6.9 [2.0] mm Hg; P < .001), leading to choroid engorgement over 3 days of bed rest (Δ area: +0.09 mm2 [95% CI, 0.04-0.13]; P = .001; Δ volume: +0.37 mm3 [95% CI, 0.19-0.55]; P = .001). Nightly LBNP caused a sustained reduction in supine central venous pressure (mean [SD], 5.7 [2.2] mm Hg to 1.2 [1.4 mm Hg]; P < .001) and attenuated the increase in choroid area (74%) (Δ: 0.02 mm2 [95% -0.02 to 0.06]; P = .01) and volume (53%) (Δ: 0.17 mm3 [95% CI, 0.01-0.34]; P = .05) compared with control. Nightly LBNP reinstated a footward fluid shift and mitigated the increase in choroid area and volume. LBNP during sleep may be an effective countermeasure for ocular remodeling and SANS during long-duration space missions.

Intramuscular lipid concentration increased in localized regions of the lumbar muscles following 60 day bedrest

BACKGROUND CONTEXTProlonged bedrest induces accumulation of intramuscular lipid concentration (ILC) in the lumbar musculature; however, spatial distribution of ILC has not been determined. Artificial gravity (AG) mitigates some adaptations induced by 60 day bedrest by creating a head-to-feet force while participants are in a supine position. PURPOSETo quantify the spatial distribution of accumulation of ILC in the lumbar musculature after 60 day bedrest, and whether this can be mitigated by AG exposure. STUDY DESIGNProspective longitudinal study. PATIENT SAMPLETwenty-four healthy individuals (8 females) participated in the study: Eight received 30 min continuous AG (cAG); Eight received 6 × 5 min AG (iAG), interspersed with rests; Eight were not exposed to AG (CRTL). OUTCOME MEASURESFrom 3T magnetic resonance imaging (MRI), axial images were selected to assess lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 intervertebral disc levels. Chemical shift-based 2‐echo lipid and/or water Dixon sequence was used to measure tissue composition. Each lumbar muscle was segmented into four equal quartiles (from medial to lateral). METHODSParticipants arrived at the facility for the baseline data collection before undergoing a 60 day strict 6° head-down tilt (HDT) bedrest period. MRI of the lumbopelvic region was conducted at baseline and Day-59 of bedrest. Participants performed all activities, including hygiene, in 6° HDT and were discouraged from moving excessively or unnecessarily. RESULTSAt the L4/L5 and L5/S1 intervertebral disc levels, 60-day bedrest induced a greater increase in ILC in medial and lateral regions (∼+4%) of the LM than central regions (∼+2%; p<.05). A smaller increase in ILC was induced in the lateral region of LES (∼+1%) at L1/L2 and L2/L3 than at the centro-medial region (∼+2%; p<.05). There was no difference between CRTL and intervention groups. CONCLUSIONSInhomogeneous spatial distribution of accumulation of ILC was found in the lumbar musculature after 60 day bedrest. These findings might reflect pathophysiological mechanisms related to muscle disuse and contribute to localized lumbar spine dysfunction. Altered spatial distribution of ILC may impair lumbar spine function after prolonged body unloading, which could increase injury risk to vulnerable soft tissues, such as the lumbar intervertebral discs. These novel results may represent a new biomarker of lumbar deconditioning for astronauts, bedridden, sedentary individuals, or those with chronic back pain. Changes are potentially modifiable but not by the AG protocols tested here.