Days Of Bed Rest Research Articles

Effects of bed-rest on urea and creatinine: correlation with changes in fat-free mass.

BackgroundBed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest.MethodsTwenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35.ResultsBed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), −2.5 mg/dL for plasma creatinine (95%CI = −3.1/−1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (−13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively).ConclusionsStudy results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.

Medical and neurologic complications of the current management strategy of angiographically negative nontraumatic subarachnoid hemorrhage patients

PurposeCommon management of angionegative subarachnoid hemorrhage includes mandatory intensive care unit stay for up to 14 days with strict bedrest, constant neurologic serial examination, invasive arterial and central line monitoring, and aneurysm rupture precautions. We evaluated the frequency of neurologic and nonneurologic complications in this patient population. MethodsThis was a retrospective chart review from July 2008 to 2011. Adult patients with International Classification of Diseases, Ninth Revision code for nontraumatic subarachnoid hemorrhage who had angiograms and cranial cat scans (CTs) were evaluated as the first screening measure. Negative screening angiograms constituted our study population and were divided into 2 groups (aneurysmal or perimesencephalic) based on the CT blood pattern. ResultsFifty-one patients met the study criteria (aneurysmal CT, n = 26; perimesencephalic CT pattern, n = 25). There were no incidences of rebleeding or mortality, and patients were discharged after a mean of 15.24 hospital days and a mean of 11 bedrest days. Seventeen patients (65%) in the aneurysmal group developed at least 1 nonneurologic complication compared with 2 patients (8%) in the perimesencephalic group (P = .001). Eleven patients in the aneurysmal group (42.3%) developed at least 1 neurologic complication compared with 1 patient (4%) in the perimesecephalic group (P = .001). ConclusionBased on our results, we propose admission to the medical floor for patients with World Federation of Neurosurgical Societies score 1 to 3, perimesencephalic CT pattern, and no hydrocephalus.

Localization of Cerebrospinal Fluid Leak in a Case of Spontaneous Intracranial Hypotension Using Dynamic Computed Tomography Myelography

EPIDURAL blood patch is the mainstay of treatment for persistent symptoms secondary to spontaneous intracranial hypotension.1 Determining the level of cerebrospinal fluid leak is thought to be an important consideration for optimal siting of the epidural blood patch injection.2 However, it is often difficult to determine the level of cerebrospinal fluid leak in spontaneous intracranial hypotension. “Dynamic” (as opposed to conventional) computed tomography myelography has recently emerged as a preferred diagnostic test for high-flow (“fast”) cerebrospinal fluid leaks, suspected by extra-arachnoid fluid on spinal magnetic resonance imaging.3 With dynamic computed tomography myelography, myelographic contrast is injected with the patient in the computed tomography scanner (tilted Trendelenburg using a wedge), followed by immediate and multiple computed tomography acquisitions.A 33-yr-old male patient presented to the emergency department with severe occipital headache. Computed tomography of the head demonstrated a chronic subdural hematoma. Head contrast magnetic resonance imaging showed diffuse dural gadolinium enhancement and a “sagging” brain. Spine magnetic resonance imaging revealed circumferential extradural fluid (“scattered” in cervical and “diffuse” in thoracic and lumbar regions). Surgical drainage of the subdural hematoma was performed. On postoperative day 1, headache symptoms were improved with no residual hematoma on repeated computed tomography of the head.However, persistent postural headaches prompted consultation of the acute pain service for evaluation and management of spontaneous intracranial hypotension. Despite lumbar epidural blood patch followed by 2 days of bed rest, headache symptoms returned on upright positioning. Dynamic computed tomography myelography performed on postoperative day 6 showed a high-flow cerebrospinal fluid leak between T4 and T5 (arrow in fig.), secondary to a midline spiculated osteophyte (arrow). Using fluoroscopic guidance, an epidural blood patch was performed between T3 and T4 (14 ml). Headache symptoms resolved and had not recurred at 12-month follow-up.The author declares no competing interests.

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

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

Effects of 60-day head-down bed rest on osteocalcin, glycolipid metabolism and their association with or without resistance training.

Bone loss and subclinical diabeteslike are developed during long-term spaceflight. Recently, it was demonstrated that bone was able to regulate energy metabolism and testosterone synthesis via osteocalcin. The aim of this study was to determine whether serum osteocalcin level is associated with glycolipid metabolism or testosterone under the influence of microgravity with or without resistive vibration exercise (RVE). A total of 14 healthy adult male volunteers (25-40years) were randomly assigned to two groups (n=7 each): control (CON) group and RVE group. Radioimmunoassay kits and ELISA kits were used for measurement of serum indices. During 60-day bed rest, serum osteocalcin of both groups increased at day 4 during bed rest. Serum OPG started decreasing and reached its lowest value at day 30 during bed rest. In control group, serum insulin increased at day 4 during bed rest. IGF-I did not change significantly during the entire period of bed rest. The serum glucose decline 10% and 14% in CON and RVE groups at day 4 during bed rest. Relatively, the same results as glucose were found in serum HDL and LDL for both groups. Leptin rose and became highest at day 60 during bed rest in both groups. The level of serum testosterone was declined in control group at day 4 during bed rest. Cortisol kept stable in both group during bed rest. By spearman correlation analysis, serum osteocalcin was significantly associated with serum insulin (P<0·05), LDL (P<0·01) and Leptin (P<0·01). Our findings suggested that the mutual regulation may exist between skeletal and energy metabolism under simulated microgravity.

Corrigendum

CorrigendaCorrigendumPublished Online:15 Jun 2014https://doi.org/10.1152/japplphysiol.zdg-1078-corr.2014Original articlesEffects of artificial gravity during bed rest on bone metabolism in humansEffects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humansMoreSectionsPDF (24 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Zwart SR, Crawford GE, Gillman PL, Kala G, Rodgers AS, Rogers A, Inniss AM, Rice BL, Ericson K, Coburn S, Bourbeau Y, Hudson E, Mathew G, DeKerlegand DE, Sams CF, Heer MA, Paloski WH, Smith SM. Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans. J Appl Physiol 107: 54–62, 2009. First published December 12, 2008; doi: 10.1152/japplphysiol.91136.2008.—For the dietary intake data reported in Table 1, errors in nutrient intake determinations resulted from the food database entries for water consumption. Specifically, bottled water was included in the calculations of intake, but subjects were actually provided with filtered tap water. This affected intake of minerals, specifically calcium, magnesium, zinc, and sodium. After identifying the issue, we analyzed several water samples for mineral content, and have recalculated the intakes of these nutrients using the analyzed results. Although the changes were relatively small and did not affect the statistical findings or the conclusions in these papers, the correction, nonetheless, had an effect on the data. The corrected dietary intake data are shown in the table below (also see corrections in companion paper: Smith SM, Zwart SR, Heer MA, Baecker N, Evans HJ, Feiveson A, Shackelford LC, LeBlanc AD. J Appl Physiol 107: , 2009).Table 1. Dietary intake before, during, and after bed restCONAGNASA Bed Rest RequirementPreBRPostPreBRPostCalcium1,502 ± 821,292 ± 77*1,537 ± 112a1,459 ± 1321,283 ± 85*1,518 ± 112*1,000–1,200Magnesium411 ± 28344 ± 24*413 ± 30408 ± 39343 ± 28*411 ± 34350Zinc15 ± 112 ± 1*15 ± 1*15 ± 112 ± 1*15 ± 1*15Sodium3,735 ± 2853,073 ± 237*3,673 ± 271*3,637 ± 2853,003 ± 226*3,587 ± 275*<3,500Values are means ± SD in mg/day, n = 7 for the control (CON) group and n = 8 for the artificial gravity (AG) group. Pre, pre-bed rest ambulatory period; BR, bed rest; Post, post-bed rest ambulatory period. Pre means are an average of 10 days immediately before bed rest, BR means are an average of 21 days of bed rest, and Post means are an average of the first 8 days after bed rest.*P < 0.001 vs. Pre.This article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesEffects of artificial gravity during bed rest on bone metabolism in humans 01 Jul 2009Journal of Applied PhysiologyEffects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans 01 Jul 2009Journal of Applied Physiology More from this issue > Volume 116Issue 12June 2014Pages 1642-1642 Copyright & PermissionsCopyright © 2014 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.zdg-1078-corr.2014History Published online 15 June 2014 Published in print 15 June 2014 Metrics

The metabolic cost of an integrated exercise program performed during 14 days of bed rest.

Exercise countermeasures designed to mitigate muscle atrophy during long-duration spaceflight may not be as effective if crewmembers are in negative energy balance (energy output > energy input). This study determined the energy cost of supine exercise (resistance, interval, aerobic) during the spaceflight analogue of bed rest. Nine subjects (eight men and one woman; 34.5 +/- 8.2 yr) completed 14 d of bed rest and concomitant exercise countermeasures. Body mass and basal metabolic rate (BMR) were assessed before and during bed rest. Exercise energy expenditure was measured during and immediately after [excess post-exercise oxygen consumption (EPOC)] each of five different exercise protocols (30-s, 2-min, and 4-min intervals, continuous aerobic, and a variety of resistance exercises) during bed rest. On days when resistance and continuous aerobic exercise were performed daily, energy expenditure was significantly greater (2879 +/- 280 kcal) than 2-min (2390 +/- 237 kcal), 30-s (2501 +/- 264 kcal), or 4-min (2546 +/- 264 kcal) exercise. There were no significant differences in BMR (pre-bed rest: 1649 +/- 216 kcal; week 1: 1632 +/- 174 kcal; week 2:1657 +/- 176 kcal) or body mass (pre-bed rest: 75.2 +/- 10.1 kg; post-bed rest: 75.2 +/- 9.6 kg). These findings highlight the importance of energy balance for long-duration crewmembers completing a high-intensity exercise program with multiple exercise sessions daily.

Calcium kinetics during bed rest with artificial gravity and exercise countermeasures.

We assessed the potential for countermeasures to lessen the loss of bone calcium during bed rest. Subjects ingested less calcium during bed rest, and with artificial gravity, they also absorbed less calcium. With exercise, they excreted less calcium. To retain bone during bed rest, calcium intake needs to be maintained. This study aims to assess the potential for artificial gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space flight. We performed two studies: (1) a 21-day bed rest (BR) study with subjects receiving 1h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study with 1h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10days of BR, and blood, urine, and feces were sampled for up to 14days post dosing. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. Less Ca was absorbed during BR, resulting in lower Ca balance in BR+AG (-6.04 ± 3.38mmol/day, P = 0.023). However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased, and there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide excretion increased in controls during BR, but not in the EX group. Markers of bone formation were not different between treatment groups for either study. Ca intake decreased during BR (by 5.4mmol/day in the AG study and 2.8mmol/day in the EX study), resulting in lower absorbed Ca. During BR (or space flight), Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca.

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria

BackgroundExposure to microgravity or immobilization results in alterations of renal function, fluid redistribution and bone loss, which couples to a rise of urinary calcium excretion. We recently demonstrated 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 and reducing calcium saturation. To investigate renal water balance adaptation during bed rest, a model to mimic the effects of microgravity on earth, the effect of changes in urinary calcium on urinary AQP2 excretion were assessed.MethodsTen healthy men (aged 21-28 years) participated in the experiment. Study design included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0 and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine samples were collected daily from day -3 to 35. Changes in blood hematocrit were used as an indirect index of plasma volume changes. AQP2 excretion was measured by ELISA.ResultsBed rest induced bone demineralization and a transient increase in urinary calcium followed by transient decrease in AQP2 excretion, which can reduce the urine concentrating ability causing plasma volume reduction. The return of calciuria to baseline was followed by a recovery of AQP2 excretion, which allows for a partial restoration of plasma volume.ConclusionsThese results further support the view that urinary calcium can modulate the vasopressin-dependent urine concentration through a down-regulation of AQP2 expression/trafficking. This mechanism could have a key role in the prevention of urine super-saturation due to hypercalciuria.

Bone loss patterns in cortical, subcortical, and trabecular compartments during simulated microgravity.

Disuse studies provide a useful model for bone adaptation. A direct comparison of these studies is, however, complicated by the different settings used for bone analysis. Through pooling and reanalysis of bone data from previous disuse studies, we determined bone loss and recovery in cortical, subcortical, and trabecular compartments and evaluated whether the study design modulated skeletal adaptation. Peripheral quantitative tomographic (pQCT) images from control groups of four disuse studies with a duration of 24, 35, 56, and 90 days were reanalyzed using a robust threshold-free segmentation algorithm. The pQCT data were available from 27 young healthy men at baseline, and at specified intervals over disuse and reambulation phases. The mean maximum absolute bone loss (mean ± 95% CI) was 6.1 ± 4.5 mg/mm in cortical, 2.4 ± 1.6 mg/mm in subcortical, and 9.8 ± 9.1 mg/mm in trabecular compartments, after 90 days of bed rest. The percentage changes in all bone compartments were, however, similar. During the first few weeks after onset of reambulation, the bone loss rate was systematically greater in the cortical than in the trabecular compartment (P < 0.002), and this was observed in all studies except for the longest study. We conclude that disuse-induced bone losses follow similar patterns irrespective of study design, and the largest mean absolute bone loss occurs in the cortical compartment, but apparently only during the first 60 days. With longer study duration, trabecular loss may become more prominent.

Leucine supplementation partially preserves neuromuscular activation during bed rest (1103.5)

We examined the effect of leucine supplementation on neuromuscular activation of sub‐maximal and maximal voluntary muscle contraction (MVC) in middle‐aged adults during 14 days of bed rest (BR). Participants (n = 10, 50.4 ± 1.0 y) in this randomized, double‐blind control 14 day BR study were assigned to a leucine (LEU, 0.06 g∙kg∙meal‐1 leucine) or control (CON) group. Surface electromyography (EMG) and torque were recorded from the vastus lateralis muscle during isometric knee extension at 20% (10s) and at 50%, 80% and 100% MVC (5s each) pre‐post BR and analyzed for root mean square (RMS) and median frequency (MF) EMG. Following BR, MVC (p &lt; 0.001) decreased in both groups with no difference between groups. RMS EMG during 100% MVC decreased in CON post‐BR (p &lt; 0.05), but was maintained in LEU and no difference in MF EMG pre‐post BR for either group (p &gt; 0.05). Despite the decrease in MVC in both groups, CON RMS EMG was higher post‐BR during all sub‐maximal contractions while LEU RMS EMG did not change at 20% and was lower at 50% and 80% MVC post‐BR. Leucine may facilitate neuronal protective mechanisms that preserve motor neuron excitability and attenuate strength loss during prolonged physical inactivity.Grant Funding Source: Supported by NSBRI NNJ08ZSA002N, NIA P30 AG024832, NIH 1UL1RR029876‐01

Influence of simulated microgravity on mechanical properties in the human triceps surae muscle in vivo. I: Effect of 120 days of bed-rest without physical training on human muscle musculo-tendinous stiffness and contractile properties in young women

PurposeThe aim of this study was to investigate the effect of a 120-day 5° head-down tilt (HDT) bed-rest on the mechanical properties of the human triceps surae muscle in healthy young women subjects.MethodsMeasurements included examination of the properties of maximal voluntary contractions (MVC), twitch contractions (P t) and tetanic contractions (P o). The difference between P o and MVC expressed as a percentage of P o and referred to as force deficiency (P d), was calculated. Electromyographic (EMG) activity in the soleus muscle, electromechanical delay (EMD) and total reaction time (TRT) were also calculated. EMD was the time interval between the change in EMG and the onset of muscle tension. Premotor time (PMT) was taken to be the time interval from the delivery of the signal to change in EMG.ResultsAfter HDT P t, MVC and P o had decreased by 11.5, 36.1, 24.4 %, respectively, P d had increased by 38.8 %. Time-to-peak tension had increased by 13.6 %, but half-relaxation time had decreased by 19.2 %. The rate of rise in isometric voluntary tension development had reduced, but no changes were observed in the electrically evoked contraction. EMD had increased by 27.4 %; PMT and TRT decreased by 21.4, and 13.7 %, respectively.ConclusionThe experimental findings indicated that neural as well as muscle adaptation occurred in response to HDT. EMD is a simple and quick method for evaluation of muscle stiffness changes and can serve as an indicator of the functional condition of the neuromuscular system.

Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males

Studies in humans show global changes in mRNA and protein expression occur in human skeletal muscle during bed rest. As microRNAs are important regulators of expression, we analysed the global microRNA expression changes in human muscle following 10 days of sustained bed rest, with the rationale that miRNAs play key roles in atrophy of skeletal muscle. We analysed expression of miRNA and selected target proteins before and after 10 days of bed rest in biopsies obtained from the vastus lateralis muscle of 6 healthy males. Fifteen of 152 miRNAs detected in human muscle tissue were differentially expressed, and all of them with exception of two were downregulated. The downregulated miRNAs include the following: miR-206, a myomir involved in function and maintenance of skeletal muscle; miR-23a, involved in insulin response and atrophy defence; and several members of the let-7 family involved in cell cycle, cell differentiation and glucose homeostasis. Predicted gene targets of these miRNAs are members of the MAPK, TNF receptor, ALK1, TGF-beta receptor and SMAD signalling pathways. All of these pathways were previously indicated to be involved in skeletal muscle response to physical inactivity. We also measured protein expression of selected miRNA targets and observed a decrease in HDAC4. Our data demonstrate that miRNAs in postural muscles are affected by sustained inactivity and unloading, as induced by prolonged bed rest, and hence are potentially involved in regulation of skeletal muscle adjustments to inactivity. We also propose new miRNAs involved in regulation of biological processes in adult human muscle.

WISE-2005: Countermeasures to prevent muscle deconditioning during bed rest in women

The objectives of this study were to evaluate the efficacy of two separate countermeasures, exercise and protein supplementation, to prevent muscle strength and lean tissue mass losses during 60 days of bed rest (BR) in women and whether countermeasure efficacy was influenced by pre-BR muscular fitness (strength, endurance, tissue mass). Twenty-four women were assigned to an exercise (EX, n = 8), a no-exercise control (CON, n = 8), or a no-exercise protein supplementation group (PROT, n = 8). EX performed supine treadmill exercise within lower body negative pressure 3-4 days/wk and maximal concentric and eccentric supine leg- and calf-press exercises 2-4 days/wk. PROT consumed a diet with elevated protein content compared with CON and EX (1.6 vs. 1.0 g·kg(-1)·day(-1)). Knee and calf isokinetic strength and endurance, isotonic leg-press strength, and leg lean mass were measured before and after BR. Post-BR knee extensor strength and endurance, ankle strength, and leg lean mass were significantly greater and leg-press strength tended to be higher in EX than in CON and PROT. Post-BR measures in PROT were not different than those in CON. Exercise countermeasure efficacy was less, and strength, endurance, and leg lean mass losses in CON and PROT were greater, in subjects who were more fit pre-BR. An exercise protocol combining resistive and aerobic exercise training protects against losses in strength, endurance, and leg lean mass in women during BR, while a nutritional countermeasure without exercise was not effective. Exercise countermeasures may require individualization to protect higher levels of strength and endurance.

Influence of exercise on the metabolic profile caused by 28 days of bed rest with energy deficit and amino acid supplementation in healthy men.

Objective Muscle loss and metabolic changes occur with disuse [i.e. bed rest (BR)]. We hypothesized that BR would lead to a metabolically unhealthy profile defined by: increased circulating tumor necrosis factor (TNF)-α, decreased circulating insulin-like-growth-factor (IGF)-1, decreased HDL-cholesterol, and decreased muscle density (MD; measured by mid-thigh computerized tomography).Methods We investigated the metabolic profile after 28 days of BR with 8±6% energy deficit in male individuals (30-55 years) randomized to resistance exercise with amino acid supplementation (RT, n=24) or amino acid supplementation alone (EAA, n=7). Upper and lower body exercises were performed in the horizontal position. Blood samples were taken at baseline, after 28 days of BR and 14 days of recovery.Results We found a shift toward a metabolically unfavourable profile after BR [compared to baseline (BLN)] in both groups as shown by decreased HDL-cholesterol levels (EAA: BLN: 39±4 vs. BR: 32±2 mg/dL, RT: BLN: 39±1 vs. BR: 32±1 mg/dL; p<0.001) and Low MD (EAA: BLN: 27±4 vs. BR: 22±3 cm2, RT: BLN: 28±2 vs. BR: 23±2 cm2; p<0.001). A healthier metabolic profile was maintained with exercise, including NormalMD (EAA: BLN: 124±6 vs. BR: 110±5 cm2, RT: BLN: 132±3 vs. BR: 131±4 cm2; p<0.001, time-by-group); although, exercise did not completely alleviate the unfavourable metabolic changes seen with BR. Interestingly, both groups had increased plasma IGF-1 levels (EAA: BLN:168±22 vs. BR 213±20 ng/mL, RT: BLN:180±10 vs. BR: 219±13 ng/mL; p<0.001) and neither group showed TNFα changes (p>0.05).Conclusions We conclude that RT can be incorporated to potentially offset the metabolic complications of BR.

How fast is recovery of impaired glucose tolerance after 21-day bed rest (NUC study) in healthy adults?

Aim. We hypothesized that 4 days of normal daily activity after 21 days of experimental bed rest (BR) will not reverse BR induced impaired glucose tolerance. Design. Glucose tolerance of seven male, healthy, untrained test subjects (age: 27.6 (3.3) years (mean (SD)); body mass: 78.6 (6.4) kg; height: 1.81 (0.04) m; VO2 max: 39.5 (5.4) ml/kg body mass/min) was studied. They stayed twice in the metabolic ward (crossover design), 21 days in bed and 7 days before and after BR each. Oral glucose tolerance tests were applied before, on day 21 of BR, and 5 and 14 days after BR. Results. On day 21 of BR, AUC120 min of glucose concentration was increased by 28.8 (5.2)% and AUC120 min of insulin by 35.9 (10.2)% (glucose: P < 0.001; insulin: P = 0.02). Fourteen days after BR, AUC120 min of serum insulin concentrations returned to pre-bed-rest concentrations (P = 0.352) and AUC120 min of glucose was still higher (P = 0.038). Insulin resistance did not change, but sensitivity index was reduced during BR (P = 0.005). Conclusion. Four days of light physical workload does not compensate inactivity induced impaired glucose tolerance. An individually tailored and intensified training regime is mandatory in patients being in bed rest to get back to normal glucose metabolism in a reasonable time frame.

Effects of bicarbonate supplementation on whole body protein metabolism and glutathione kinetics in healthy young volunteers during 21 days of experimental bed rest

Effects of bicarbonate supplementation on whole body protein metabolism and glutathione kinetics in healthy young volunteers during 21 days of experimental bed rest

Leptin signaling in skeletal muscle after bed rest in healthy humans

This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system. Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot. After bed rest basal insulin concentration was increased by 53% (P < 0.05), the homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin concentration by 35% (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest. One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.

Potential regulation of human muscle plasticity by MLC2 post-translational modifications during bed rest and countermeasures

This study investigated the effects of a 60-day bed rest with or without countermeasures on muscular phenotype and post-translational modifications of the regulatory Myosin Light Chain 2 (MLC2) protein. Soleus biopsies were obtained from female subjects before and after bed rest. Control subjects were assigned only to bed rest (BR), BR+Ex subjects were submitted to combined aerobic and resistive exercises, and BR+Nut to nutritional leucine and valine diet. We determined Myosin Heavy Chains (MHC) and MLC2 composition of muscles using 1D SDS–PAGE. MLC2 phosphorylation was measured on 2D gels and O-N-Acetyl Glucosaminylation (O-GlcNAc) level of MLC2 was determined. Our results showed a slow-to-fast shift of MHC and MLC2 isoforms in BR and BR+Nut while BR+Ex combinations prevented these phenotype changes. After BR, the MLC2 phosphorylation state was increased while the global MLC2 glycosylation level was decreased. Exercises prevented the variations of phosphorylation and glycosylation observed after BR whereas nutrition had no effects. These results suggested an interplay between phosphorylation and glycosylation of MLC2, which might be involved in the development of muscle atrophy and associated changes. These findings of differential responses to exercises and nutrition protocols were discussed with implications for future prescription models to preserve muscle against long-term unloading.

Prolonged physical inactivity leads to a drop in toe skin temperature during local cold stress

The purpose was to examine the effects of a prolonged period of recumbency on the toe temperature responses during cold-water foot immersion. Ten healthy males underwent 35 days of horizontal bed rest. The right foot of the subjects was assigned as the experimental (EXP) foot. To prevent bed rest-induced vascular deconditioning in the left control foot (CON), a sub-atmospheric vascular pressure countermeasure regimen was applied on the left lower leg for 4 × 10 min every second day. On the first (BR-1) and the last (BR-35) day of the bed rest, subjects performed two 30 min foot immersion tests in 8 °C water, one with the EXP foot and the other with the CON foot. The tests were conducted in counter-balanced order and separated by at least a 15 min interval. At BR-35, the average skin temperature of the EXP foot was lower than at BR-1 (-0.8 °C; P = 0.05), a drop that was especially pronounced in the big toe (-1.6 °C; P = 0.05). In the CON foot, the average skin temperature decreased by 0.6 °C in BR-35, albeit the reduction was not statistically significant (P = 0.16). Moreover, the pressure countermeasure regimen ameliorated immersion-induced thermal discomfort for the CON foot (P = 0.05). Present findings suggest that severe physical inactivity exaggerates the drop in toe skin temperature during local cold stress, and thus might constitute a potential risk factor for local cold injury.