Days Of Bed Rest Research Articles

Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise.

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle.

In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082mm×0.082mm×0.082mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture). Materials and methodsIn the Berlin Bed Rest Study-2, 23 male subjects (20–50 YO) were maintained 60 days under restricted bed rest (6° HDT) aiming to test a - for this study specifically designed - vibration resistive exercise regime for maintenance of bone mass and muscle functionality at normal levels (base line measurements). For comparison a resistive exercise without vibration and a control group were included. Base line HR-pQCT measurements (3 days before bed rest: base line), as well as during 30 days bed rest (BR30 and BR59, 3 days of recovery (R3), R15, R30, R90, R180, R360, and R720 were performed. CT-scan voxels were converted into finite elements (hexa-82µm edge length) for calculating in vivo compressive stiffness during the experiment duration. Histograms of stresses and strains distributions as well as anatomical regions susceptible for mechanical failure were identified and compared. Results:Resistive vibration exercises (RVE) were able to maintain in the majority of the subjects compressive bone strength as determined after modelling a compressive test using finite element models. Compressive bone stiffness using FEA was monitored through analysis of the internal deformation on the trabecular structures and cortical bone, reaction forces, and minimum principal strains on the in vivo CT measured bone regions during the experiment duration. Stress distributions (main stresses) and von Mises stress distribution remained comparable with those determined in the base line measurements for the RVE-group. However, no major differences were found in the group with resistive exercise training alone. Without mechanical stimuli an increment of bone regions with high stress concentration was observed and a reduction of up to 10% of bone compressive stiffness was quantified by using subject-specific finite-element analysis. Anatomically von Mises stress concentrations, thus bone regions susceptible to fail mechanically, were observed at the center of the cancellous bone and at the antero- posterior region of the cortical bone. Conclusions:Finite element simulations from bed rest studies are an invaluable tool to determine subject-specific in vivo compressive stiffness and anatomical mechanically compromised regions under controlled mechanical conditions (unloading) which - until now - are not possible to be determined with any other method. Vibration exercise combined with a resistive compressive force was able to maintain bone structure and density even during 60 days of bed rest.

The effect of alternate-day caloric restriction on the metabolic consequences of 8 days of bed rest in healthy lean men: a randomized trial.

Alternate-day caloric restriction without overall energy reduction does not ameliorate the metabolic impairment induced in lean men by 8 days of bed rest.

Neuromuscular electrical stimulation prior to presleep protein feeding stimulates the use of protein-derived amino acids for overnight muscle protein synthesis.

Neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. Here we demonstrate that in older men after a day of bed rest, the application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis by 18% compared with presleep protein feeding only.

Short-Term Intensive Rehabilitation Induces Recovery of Physical Function After 7 Days of Bed Rest in Older Adults

Purpose: Hospitalization can result in functional loss, especially in older adults. The purpose of the study was to determine the effect of intensive rehabilitation on changes in physical function in healthy older subjects after 1 week of bed rest and 3 days of rehabilitation. Methods: Six healthy subjects older than 60 years completed 7 days of bed rest followed by 3 days of rehabilitation including stretching, strengthening, balance, gait, and stair climbing. Results: Bed rest reduced the distance walked over 6 minutes, slowed gait speeds, and increased sit-to-stand times. Muscle flexibility and isokinetic quadriceps strength varied after bed rest. Three days of rehabilitation restored outcomes measures to baseline levels. Conclusions: A short bout of focused rehabilitation after a week of bed rest restored physical function measures to pre-bed rest levels in healthy older subjects. Similar training protocols may result in increased functional measures in older hospitalized patients.

Effect of alterations in blood volume with bed rest on glucose tolerance.

Bed rest leads to rapid impairments in glucose tolerance. Plasma volume and thus dilution space for glucose are also reduced with bed rest, but the potential influence on glucose tolerance has not been investigated. Accordingly, the aim was to investigate whether bed rest-induced impairments in glucose tolerance are related to a concomitant reduction in plasma volume. This hypothesis was tested mechanistically by restoring plasma volume with albumin infusion after bed rest and parallel determination of glucose tolerance. Fifteen healthy volunteers (age 24 ± 3 yr, body mass index 23 ± 2 kg/m2, maximal oxygen uptake 44 ± 8 ml·min-1·kg-1; means ± SD) completed 4 days of strict bed rest. Glucose tolerance [oral glucose tolerance test (OGTT)] and plasma and blood volumes (carbon monoxide rebreathing) were assessed before and after 3 days of bed rest. On the fourth day of bed rest, plasma volume was restored by means of an albumin infusion prior to an OGTT. Plasma volume was reduced by 9.9 ± 3.0% on bed rest day 3 and area under the curve for OGTT was augmented by 55 ± 67%. However, no association (R2 = 0.09, P = 0.33) between these simultaneously occurring responses was found. While normalization of plasma volume by matched albumin administration (408 ± 104 ml) transiently decreased (P < 0.05) resting plasma glucose concentration (5.0 ± 0.4 to 4.8 ± 0.3 mmol/l), this did not restore glucose tolerance. Bed rest-induced alterations in dilution space may influence resting glucose values but do not affect area under the curve for OGTT.

Relationship between hospitalization and functional and cognitive impairment in hospitalized older adults patients

ABSTRACTObjectives: To study changes in the cognitive status and dependency of patients aged over 65 years during hospitalization for bone fracture and how these changes relate to the total number of days of admission and absolute rest during hospitalization. Along with cognitive decline, musculoskeletal disorders are considered key factors in this patient population. As well as requiring hospital admission and/or surgical treatment, fractures increase the risk factors that contribute to disability and dependency in older adults.Method: A longitudinal case-series study with repeated follow-up assessments was conducted. The sample consisted of 259 older adults. The following tests were administered: Barthel index, Lawton-Brody's scale, Phototest, and informant questionnaire on cognitive decline in the elderly.Results: The main variable which fosters functional dependency, cognitive decline, and functional loss and diminishes functional gain (both in the hospital and at home) is the number of days of bed rest during hospitalization.Conclusions: The present study reveals that the greater impact on levels of functional dependency and cognitive decline comes from the patient's days of bed rest in hospital, rather than the total days of hospitalization. These findings could be taken into consideration when discussing post-discharge functional recovery.

Morbidity After Inguinal Lymph Node Dissections: It Is Time for a Change

BackgroundInguinal lymph node dissection (ILND) for stage 3 melanoma is accompanied by high wound complication rates. During the past decades, several changes in perioperative care have been instituted to decrease the incidence of these complications. This study aimed to evaluate the effect of these different care protocols on wound complications after ILND.MethodsA retrospective analysis of prospectively collected data was performed with 240 patients who underwent an ILND in the University Medical Center Groningen between 1989 and 2014. Four groups with different treatment protocols were analyzed: A (≥10 days of bed rest with a Bohler Braun splint), B (10 days of bed rest without a splint), C (5 days of bed rest), and D (1 day of bed rest). The effect of early mobilization, abolishment of the Bohler Braun splint and postural restrictions, and the introduction of prophylactic antibiotics were analyzed.ResultsOne or more wound complications occurred in 51.2 % of the patients including wound infection (29.8 %), seroma (21.5 %), wound necrosis (13.6 %), and hematoma (5 %). In consecutive periods, respectively 44.4, 60.3, 44.9 and 55.2 % of the patients experienced wound complications. None of the instituted changes in protocols led to a decrease in wound complications.ConclusionChanges in perioperative care protocols did not affect the rate of wound complications. Perhaps a change in the surgical procedure itself can lead to the necessary reduction of wound complications after ILND.

Whey protein with potassium bicarbonate supplement attenuates the reduction in muscle oxidative capacity during 19 days of bed rest.

The effectiveness of whey protein plus potassium bicarbonate-enriched diet (WP+KHCO3) in mitigating disuse-induced changes in muscle fiber oxidative capacity and capillarization was investigated in a 21-day crossover design bed rest study. Ten healthy men (31 ± 6 yr) once received WP+KHCO3 and once received a standardized isocaloric diet. Muscle biopsies were taken 2 days before and during the 19th day of bed rest (BR) from the soleus (SOL) and vastus lateralis (VL) muscle. Whole-body aerobic power (V̇o2 max), muscle fatigue, and isometric strength of knee extensor and plantar flexor muscles were monitored. Muscle fiber types and capillaries were identified by immunohistochemistry. Fiber oxidative capacity was determined as the optical density (OD) at 660 nm of succinate dehydrogenase (SDH)-stained sections. The product of fiber cross-sectional area and SDH-OD (integrated SDH) indicated the maximal oxygen consumption of that fiber. The maximal oxygen consumption supported by a capillary was calculated as the integrated SDH in its supply area. BR reduced isometric strength of knee extensor muscles (P < 0.05), and the fiber oxidative capacity (P < 0.001) and V̇o2 max (P = 0.042), but had no significant impact on muscle capillarization or fatigue resistance of thigh muscles. The maximal oxygen consumption supported by a capillary was reduced by 24% in SOL and 16% in VL (P < 0.001). WP+KHCO3 attenuated the disuse-induced reduction in fiber oxidative capacity in both muscles (P < 0.01). In conclusion, following 19 days of bed rest, the decrement in fiber oxidative capacity is proportionally larger than the loss of capillaries. WP+KHCO3 appears to attenuate disuse-induced reductions in fiber oxidative capacity.

Importance of early mobilisation in critical care patients.

of any critical care team is to minimise length of admission and expedite safe discharge from hospital. In reality, the journey for a critical care patient is fraught with risks involving both predictable and some unforeseen complications. From my experiences on critical care units, it quickly became apparent that maintaining a progressive path towards recovery was one of the greatest challenges in patient care. This could be attributed to the complex and systemic nature of critical illness, which will inevitably result in continual changes in the patient’s condition. These circumstances often leave the patient with life-changing chronic conditions, such as psychological issues or functional disabilities after weeks or months of immobility. Indeed, research strongly suggests that lean muscle mass is significantly diminished after only 10 days of bed rest, which, while it did not always affect functional ability, did have a detrimental effect on muscle power and stamina (Kortebein et al, 2008). Unsurprisingly, this effect was magnified in older patients, where muscle mass is lost at a greater rate than in their younger counterparts (English and Paddon-Jones, 2010). Every critical care nurse will be familiar with this process. It is always distressing to observe a patient overcome with exhaustion while attempting the most simple of movements, such as rolling in bed. However, we must not forget that we are only observing the early stages of their difficulties and for some the road to recovery may never be fully travelled. There is evidence to suggest that critical care patients remain unemployed 12 months after hospital discharge with a significant proportion still struggling to sustain employment after 5 years (Schweickert and Kress, 2011). The reason is that muscle-mass loss has left them with a chronic reduction in exercise tolerance, Importance of early mobilisation in critical care patients

Individual Variability in Aerobic Fitness Adaptations to 70 Days of Bed Rest and Exercise Training

Changes in maximal aerobic capacity (VO2pk) in response to exercise training and disuse are highly variable between individuals. Factors (e.g., lean mass, daily activity, diet, sleep, stress) that could contribute to the observed variability are often not controlled in studies. The NASA bed rest (BR) studies use a highly controlled, hospital-based model as an analog of spaceflight. In this study, diet, hydration, physical activity, and light/dark cycles were precisely controlled and provided the opportunity to investigate individual variability. PURPOSE: Evaluate the effects of exercise intensity and lean mass on change in VO2pk during 70 days of BR or BR + exercise. METHODS: Subjects completed 70 days of BR (CON, n=9) or BR + exercise (EX, n=17). The exercise prescription included 6 d/wk of aerobic exercise at 70 – 100% of VO2pk and 3 d/wk of lower-body-resistance exercise. Subjects were monitored 24 h/d. VO2pk and lean mass (iDXA) were measured pre and post BR. ANOVA was used to evaluate changes in VO2pk pre to post BR. Subjects were retrospectively divided into high and low responders based on change in VO2pk (CON > 20% loss, n=5; EX >10% loss, n=4, or > 5% gain, n=4) to further understand individual variability. RESULTS: VO2pk decreased from pre to post BR in CON (P<0.05) and was maintained in EX; however, significant individual variability was observed (CON: -22%, range: -39% to -1%; EX: -2%, range: -16% to 13%). The overlap in ranges between groups included 3 CON who experienced smaller reductions in VO2pk (<16%) than the worst responding EX subjects. Individual variability was maintained when VO2pk was normalized to lean mass (range, CON: -34% to -6%; EX: -16% to 11%), and the overlap included 5 CON with smaller reductions in VO2pk than the worst responding EX subjects. High CON responders to disuse also lost the most lean mass; however, this relationship was not present in EX (i.e. the largest gains/losses in lean mass were observed in both high and low responders). Change in VO2pk was not related to exercise intensity. CONCLUSION: Change in VO2pk in response to disuse and exercise was highly variable among individuals, even in this tightly controlled study. Lean mass loss accounts for a significant degree of the variability in CON; however, in EX, training induced changes in VO2pk appear unrelated to lean mass or exercise intensity.

14 days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle‐aged adults

We examined the effect of 14 days of bed rest on skeletal muscle satellite cell content and fiber type atrophy and in middle‐aged adults. Bed rest, a ground‐based space flight analog, induces robust atrophy of skeletal muscle, an effect that is exacerbated with increasing age. With the average age of astronauts increasing, we wanted to determine the mechanistic changes during bed rest on an understudied age‐cohort. Muscle biopsies were obtained from the vastus lateralis of healthy middle‐aged adults (n=7 [4M;3F]; age: 51.0±0.6 y) before (Pre‐BR) and after (Post‐BR) 14 days of bed rest. Immunohistochemical analyses were used to quantify myosin heavy chain (MyHC) isoform expression, cross‐sectional area (CSA), satellite cell and myonuclear content and capillary density. Peak oxygen consumption and body composition were measured Pre‐ and Post‐BR. Post‐BR MyHC Type 2a fiber percentage was reduced and mean CSA decreased in all fiber types (25% decrease; P&lt;0.05). Satellite cell content was also reduced Post‐BR (41% decrease; P&lt;0.05), while Pre‐BR Type 2 satellite cell frequency was correlated with the decline in leg lean mass as measured by DXA scan. A decline in capillary density was observed Post‐BR (25% decrease; P&lt;0.05), and Post‐BR capillary density was associated with Post‐BR peak oxygen consumption. A subtle decline in myonuclear content occurred during bed rest. The rapid maladaptation of skeletal muscle to 14 days of mechanical unloading in middle‐aged adults emphasizes the need for appropriate counter measures to preserve muscle function in astronauts.Support or Funding InformationFunded by NSBRI grant NNJ08ZSA002N, NIH R01NR012973 (Paddon‐Jones), a Texas Space Grant Consortium Fellowship (English), NIH grant T32HD007539, and in part by the UTMB Claude D. Pepper Older Americans Independence Center NIH/NIA grant #P30 AG024832 and grant 1UL1RR029876‐01 from the National Center for Research Resources. The study was conducted with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).

Lower Body Negative Pressure Treadmill Exercise Attenuates Simulated Space Flight‐Induced Reductions of Balance Abilities in Males but not Females

Spaceflight causes sensorimotor adaptations that result in balance deficiencies upon return to a gravitational environment. Lower Body Negative Pressure (LBNP) treadmill exercise has been shown to protect against deconditioning in various other physiological systems during simulated spaceflight. Therefore, we hypothesized that LBNP treadmill exercise prevents balance losses in both male and female identical twins during 30 days of 6° head‐down‐tilt (HDT) bed rest. Fifteen (8M and 7F) identical twin sets participated in 30 days of bed rest. Within each twin pair, one twin was randomly assigned to an exercise group that performed 40 min of supine LBNP treadmill exercise set to generate 1.0–1.2 body weight, followed by 5 min of static LBNP, 6 days/wk. Their identical sibling was assigned to a non‐exercise control group. Before and immediately after bed rest, subjects completed standing and walking rail balance tests with eyes open and eyes closed. In control subjects, standing rail balance times (men: −42%, women: −40%), rail walk distances (men: −44%, women: −32%), and rail walk times (men: −34%, women: −31%) significantly decreased after bed rest. Compared to controls, subjects in the LBNP treadmill exercise group showed significantly attenuated losses of standing rail balance time, with prevention of 63% of the loss in men, but without a significant prevention in women (41%). In addition, LBNP treadmill exercise mitigated decreases in rail walk time in men, but not in women. Therefore, treadmill exercise within LBNP during spaceflight may maintain balance control; yet this protective effect may, to some extent, depend on gender.Support or Funding InformationThis study was funded by NASA grants NAG 9‐1425, NCC2‐1133, NNX10AM18G, and NNX13AJ12G, NIH grant to the UCSD GCRC M01 RR00827. BRM was supported by National Space Biomedical Research Institute through NCC 9‐58. We thank our outstanding twins and staff at the UCSD General Clinical Research Center, as well as the UCSD Faculty Mentorship Program and the 2015 Julia Brown Research Scholarship.

Age-related differences in plasma BDNF levels after prolonged bed rest.

Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and has been implicated in brain resistance to insults. Murine studies have demonstrated increased hippocampal concentration after acute immobilization and decreased concentration after chronic immobilization. In humans, chronic stress and sedentary lifestyle result in decreased plasma BDNF levels, but there no data exist regarding acute immobilization. The aim of our study was to evaluate age-related responses [comparing 7 younger subjects (age 23 ± 3 yr) and 8 older subjects (age 60 ± 4 yr)] of plasma BDNF before (baseline data collection, BDC) and after 14 days (BR14) of horizontal bed rest (BR). At BDC, BDNF levels were not different between the two groups (P = 0.101), although at BR14, BDNF levels were higher in older subjects (62.02 ± 18.31) than in younger subjects (34.36 ± 15.24 pg/ml) (P = 0.002). A general linear model for repeated measures showed a significant effect of BR on BDNF (P = 0.002). The BDC BDNF levels correlated with fat-free mass in both populations (ALL) (R = 0.628, P = 0.012), (older, R = 0.753, P = 0.031; younger, R = 0.772, P = 0.042), and with total cholesterol in ALL (R = 0.647, P = 0.009) and older study subjects (R = 0.805, P = 0.016). At BR14, BDNF correlated with total cholesterol (R = 0.579, P = 0.024) and age (R = 0.647, P = 0.009) in ALL. With an increase in age, the brain could become naturally less resistant to acute stressors, including the detrimental effects of prolonged bed rest, and thus the increase in BDNF in the older study group might reflect a protective overshooting of the brain to counteract the negative effects in such conditions.

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-day bed rest in women.

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 ± 4.5%), compared with controls (-16.6 ± 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.

Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults.

Bed rest, a ground-based spaceflight analog, induces robust atrophy of skeletal muscle, an effect that is exacerbated with increasing age. We examined the effect of 14 days of bed rest on skeletal muscle satellite cell content and fiber type atrophy in middle-aged adults, an understudied age demographic with few overt signs of muscle aging that is representative of astronauts who perform long-duration spaceflight. Muscle biopsies were obtained from the vastus lateralis of healthy middle-aged adults [n= 7 (4 male, 3 female); age: 51 ± 1 yr] before (Pre-BR) and after (Post-BR) 14 days of bed rest. Immunohistochemical analyses were used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell and myonuclear content, and capillary density. Peak oxygen consumption, knee extensor strength, and body composition were also measured Pre-BR and Post-BR. Post-BR MyHC type 2a fiber percentage was reduced, and mean CSA decreased in all fiber types (-24 ± 5%;P< 0.05). Satellite cell content was also reduced Post-BR (-39 ± 9%;P< 0.05), and the change in satellite cell content was significantly correlated with the change in mean fiber CSA (r(2)= 0.60;P< 0.05). A decline in capillary density was observed Post-BR (-23 ± 6%;P< 0.05), and Post-BR capillary content was significantly associated with Post-BR peak aerobic capacity (r(2)= 0.59;P< 0.05). A subtle decline in myonuclear content occurred during bed rest (-5 ± 1%;P< 0.05). The rapid maladaptation of skeletal muscle to 14 days of mechanical unloading in middle-aged adults emphasizes the need for robust countermeasures to preserve muscle function in astronauts.

PlanHab: the combined and separate effects of 16 days of bed rest and normobaric hypoxic confinement on circulating lipids and indices of insulin sensitivity in healthy men.

PlanHab is a planetary habitat simulation study. The atmosphere within future space habitats is anticipated to have reduced Po2, but information is scarce as to how physiological systems may respond to combined exposure to moderate hypoxia and reduced gravity. This study investigated, using a randomized-crossover design, how insulin sensitivity, glucose tolerance, and circulating lipids were affected by 16 days of horizontal bed rest in normobaric normoxia [NBR: FiO2 = 0.209; PiO2 = 133.1 (0.3) mmHg], horizontal bed rest in normobaric hypoxia [HBR: FiO2 = 0.141 (0.004); PiO2 = 90.0 (0.4) mmHg], and confinement in normobaric hypoxia combined with daily moderate intensity exercise (HAMB). A mixed-meal tolerance test, with arterialized-venous blood sampling, was performed in 11 healthy, nonobese men (25-45 yr) before (V1) and on the morning ofday 17of each intervention (V2). Postprandial glucose and c-peptide response were increased at V2 of both bed rest interventions (P< 0.05 in each case), with c-peptide:insulin ratio higher at V2 in HAMB and HBR, both in the fed and fasted state (P< 0.005 in each case). Fasting total cholesterol was reduced at V2 in HAMB [-0.47 (0.36) mmol/l;P< 0.005] and HBR [-0.55 (0.41) mmol/l;P< 0.005]. Fasting HDL was lower at V2 in all interventions, with the reduction observed in HBR [-0.30 (0.21) mmol/l] greater than that measured in HAMB [-0.13 (0.14) mmol/l;P< 0.005] and NBR [-0.17 (0.15) mmol/l;P< 0.05]. Hypoxia did not alter the adverse effects of bed rest on insulin sensitivity and glucose tolerance but appeared to increase insulin clearance. The negative effect of bed rest on HDL was compounded in hypoxia, which may have implications for long-term health of those living in future space habitats.

The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers.

Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect.

Vibration mechanosignals superimposed to resistive exercise result in baseline skeletal muscle transcriptome profiles following chronic disuse in bed rest.

Disuse-induced muscle atrophy is a major concern in aging, in neuromuscular diseases, post-traumatic injury and in microgravity life sciences affecting health and fitness also of crew members in spaceflight. By using a laboratory analogue to body unloading we perform for the first time global gene expression profiling joined to specific proteomic analysis to map molecular adaptations in disused (60 days of bed rest) human soleus muscle (CTR) and in response to a resistive exercise (RE) countermeasure protocol without and with superimposed vibration mechanosignals (RVE). Adopting Affymetrix GeneChip technology we identified 235 differently transcribed genes in the CTR group (end- vs. pre-bed rest). RE comprised 206 differentially expressed genes, whereas only 51 changed gene transcripts were found in RVE. Most gene transcription and proteomic changes were linked to various key metabolic pathways (glycolysis, oxidative phosphorylation, tricarboxylic acid (TCA) cycle, lipid metabolism) and to functional contractile structures. Gene expression profiling in bed rest identified a novel set of genes explicitly responsive to vibration mechanosignals in human soleus. This new finding highlights the efficacy of RVE protocol in reducing key signs of disuse maladaptation and atrophy, and to maintain a close-to-normal skeletal muscle quality outcome following chronic disuse in bed rest.

A re-analysis of the 1968 Saltin etal. "Bedrest" paper.

In 1968, Saltin et al. published a landmark paper describing the alterations in VO2max resulting from two sequential interventions--20 days of bed rest and almost 8 weeks of training. They concluded that bed rest reduced VO2max through reductions in maximal cardiac output, while training enhanced VO2max by an equal combination of increased maximal cardiac output and increased arterio-venous [O2] difference (A-V Δ [O2]). At the time, A-V Δ [O2] was taken as an index of peripheral (skeletal muscle) adaptation. A key interpretive element that was not featured was consideration of how alterations in cardiac output affect the O2 extraction process secondary to changes in red cell transit time through the muscle microcirculation, even in the absence of adaptive changes in the skeletal muscles per se. For the 2015 Saltin Symposium, it was therefore thought appropriate to re-examine the 1968 O2 transport data and re-evaluate the roles central cardiovascular and peripheral muscle changes after bed rest and training allowing for their interaction. The analysis supports the conclusion that bed rest reduced VO2max mainly through reduction in cardiac output, but after training, it is proposed that the 1968 conclusions should be modified: the majority of the increase in VO2max from the control state can be attributed to an improvement in diffusive unloading of O2 from the muscle microcirculation, with a much smaller role for enhanced blood flow.