Short-term Bed Rest Research Articles

Short-Term Bed Rest is not a Risk Factor for Venous Thromboembolism After Endoscopic Skull Base Surgery

IntroductionDeep venous thromboembolisms (DVT) increase morbidity in postoperative patients, and no current guidelines identify which patients undergoing endoscopic endonasal approach (EEA) to the skull base may be at increased risk. Postoperative care for these patients often includes a period of inactivity to prevent transient ICP shifts which may impact skull base reconstruction. We seek to characterize if postoperative bedrest puts EEA patients at increased risk of developing thromboembolic complications. MethodsRetrospective chart review of patients undergoing intradural surgery with primary skull base reconstruction for intraoperative CSF leak via EEA for any skull base pathology between July 2018 and May 2024 was performed yielding 221 patients who met inclusion criteria. Univariate and multivariable regression were performed with patient demographics, extent of approach, intraoperative leak flow rate, bedrest duration, presence and length of postoperative lumbar drainage (LD), and use of postoperative mechanical VT prophylaxis. ResultsThe mean age of included patients was 52.6 ± 16.8 years, 48% were male, and 3.6% of patients had DVTs. Age (OR 1.01, 95% CI 0.96-1.06, p=0.83), sex (OR 0.40, 95% CI 0.05-2.19, p=0.31), BMI (OR 0.98, 95% CI 0.87-1.07, p=0.74), extended approach (OR 0.80, 95% CI 0.13-4.36, p=0.80), CSF leak flow rate (OR 5.71, 95% CI 0.77-118.90, p=0.14), bedrest duration (OR 1.06, 95% CI 0.77-1.27, p=0.60), and presence of LD (OR 1.10, 95% CI 0.55-2.02, p=0.76) were not significant predictors of postoperative VTE incidence on multivariable analysis. ConclusionShort-term bedrest after EEA is not a risk factor for development of VTE in the immediate postoperative period.

Five days of bed rest in young and old adults: Retainment of skeletal muscle mass with neuromuscular electrical stimulation.

The consequences of short-term disuse are well known, but effective countermeasures remain elusive. This study investigated the effects of neuromuscular electrical stimulation (NMES) during 5 days of bed rest on retaining lower limb muscle mass and muscle function in healthy young and old participants. One leg received NMES of the quadriceps muscle (3 × 30min/day) (NMES), and the other served as a control (CON). Isometric quadriceps strength (MVC), rate of force development (RFD), lower limb lean mass, and muscle thickness were assessed pre-and post-intervention. Muscle thickness remained unaltered with NMES in young and increased in old following bed rest, while it decreased in CON legs. In old participants, mid-thigh lean mass (MTLM) was preserved with NMES while decreased in CON legs. In the young, only a tendency to change with bed rest was detected for MTLM. MVC and early-phase RFD decreased in young and old, irrespective of NMES. In contrast, late-phase RFD was retained in young participants with NMES, while it decreased in young CON legs, and in the old, irrespective of NMES. NMES during short-term bed rest preserved muscle thickness but not maximal muscle strength. While young and old adults demonstrated similar adaptive responses in preventing the loss of skeletal muscle thickness, RFD was retained in the young only.

Bed-rest and exercise remobilisation: concurrent adaptations in muscle glucose and protein metabolism

Bed rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events has not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilisation (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. Ten healthy males (24±1 years, body mass index (BMI) 22.7±0.6) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5x30 maximal voluntary single leg isokinetic knee-extensions at 90o/sec each day. An isoenergetic diet was maintained throughout the study (30% fat,15% protein, 55% carbohydrate). Resting LGU was calculated from arteriovenous-venous difference across the leg and leg blood flow during the steady-state of a 3 hr hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) measured pre BR, post BR and after remobilisation. Glycogen content was measured in Vastus Lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging pre BR, post BR and after remobilisation. Cumulative myofibrillar protein fractional synthesis rate (FSR), and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilisation using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. Compared with pre BR, there was a 45% decline in insulin-stimulated LGU (p<0.05) after BR, which was paralleled by a reduction in insulin stimulated leg blood flow (p<0.01) and removal of insulin stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (p<0.05) and a 2.5% decrease in LMV (p<0.01) during BR, along with a 30% decline in whole-body muscle myofibrillar protein breakdown after 2 days BR (p<0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ERS (p<0.01, p<0.01; respectively), but not by ambulation alone. However, insulin stimulated LGU and muscle glycogen storage were not restored by ESR. Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasising the importance of exercise rehabilitation following even short-term BR. This study was supported by the Biotechnology and Biological Sciences Research Council (BB/P005004/1), the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis (grant no. 21595), and the National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. Ten healthy males (24±1years, body mass index 22.7±0.6kg/m2) underwent 3days of BR, followed immediately by 3days of ESR consisting of 5×30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P<0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P<0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P<0.05) and a 2.5% decrease in LMV (P<0.01) during BR, along with a 30% decline in whole-body MPB after 2days of BR (P<0.05). Myofibrillar protein FSR and LMV were restored by 3days of ESR (P<0.01 and P<0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

The impact of bed rest on human skeletal muscle metabolism

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

Management of Osteoporotic Vertebral Fracture: Review Update 2022.

A vertebral fracture is the most common type of osteoporotic fracture. Osteoporotic vertebral fractures (OVFs) cause a variety of morbidities and deaths. There are currently few "gold standard treatments" outlined for the management of OVFs in terms of quantity and quality. Conservative treatment is the primary treatment option for OVFs. The treatment of pain includes short-term bed rest, analgesic medication, anti-osteoporotic medications, exercise, and a brace. Numerous reports have been made on studies for vertebral augmentation (VA), including vertebroplasty and kyphoplasty. There is still debate and controversy about the effectiveness of VA in comparison with conservative treatment. Until more robust data are available, current evidence does not support the routine use of VA for OVF. Despite the fact that the majority of OVFs heal without surgery, 15%-35% of patients with an unstable fracture, persistent intractable back pain, or severely collapsed vertebra that causes a neurologic deficit, kyphosis, or chronic pseudarthrosis frequently require surgery. Because no single approach can guarantee the best surgical outcomes, customized surgical techniques are required. Surgeons must stay current on developments in the osteoporotic spine field and be open to new treatment options. Osteoporosis management and prevention are critical to lowering the risk of future OVFs. Clinical studies on bisphosphonate's effects on fracture healing are lacking. Teriparatide was intermittently administered, which dramatically improved spinal fusion and fracture healing while lowering mortality risk. According to the available literature, there are no standard management methods for OVFs. More multimodal approaches, including conservative and surgical treatment, VA, and medications that treat osteoporosis and promote fracture healing, are required to improve the quality of the majority of guidelines.

Peripheral nerve adaptations to 10 days of horizontal bed rest in healthy young adult males.

Space analogs, such as bed rest, are used to reproduce microgravity-induced morphological and physiological changes and can be used as clinical models of prolonged inactivity. Nevertheless, nonuniform decreases in muscle mass and function have been frequently reported, and peripheral nerve adaptations have been poorly studied, although some of these mechanisms may be explained. Ten young healthy males (18-33 yr) underwent 10 days of horizontal bed rest. Peripheral neurophysiological assessments were performed bilaterally for the dominant (DL) and nondominant upper and lower limbs (N-DL) on the 1st and 10th day of bed rest, including ultrasound of the median, deep peroneal nerve (DPN), and common fibular nerve (CFN) , as well as a complete nerve conduction study (NCS) of the upper and lower limbs. Consistently, reduced F waves, suggesting peripheral nerve dysfunction, of both the peroneal (DL: P = 0.005, N-DL: P = 0.013) and tibial nerves (DL: P = 0.037, N-DL: P = 0.005) were found bilaterally, whereas no changes were observed in nerve ultrasound or other parameters of the NCS of both the upper and lower limbs. In these young healthy males, only the F waves, known to respond to postural changes, were significantly affected by short-term bed rest. These preliminary results suggest that during simulated microgravity, most changes occur at the muscle or central nervous system level. Since the assessment of F waves is common in clinical neurophysiological examinations, caution should be used when testing individuals after prolonged immobility.

Move it or lose it: limb immobilisation results in impaired postprandial skeletal muscle glucose uptake.

Move it or lose it: limb immobilisation results in impaired postprandial skeletal muscle glucose uptake.

Current Concepts in the Management of Osteoporotic Vertebral Fractures: A Narrative Review.

Vertebral fractures are the most common type of osteoporotic fracture and can increase morbidity and mortality. To date, the guidelines for managing osteoporotic vertebral fractures (OVFs) are limited in quantity and quality, and there is no gold standard treatment for these fractures. Conservative treatment is considered the primary treatment option for OVFs and includes pain relief through shortterm bed rest, analgesics, antiosteoporotic drugs, exercise, and braces. Studies on vertebral augmentation (VA) including vertebroplasty and kyphoplasty have been widely reported, but there is still debate and controversy regarding the effectiveness of VA when compared with conservative treatment, and the routine use of VA for OVF is not supported by current evidence. Although most OVFs heal well, approximately 15%–35% of patients with unstable fractures, chronic intractable back pain, severely collapsed vertebra (leading to neurological deficits and kyphosis), or chronic pseudarthrosis frequently require surgery. Given that there is no single technique for optimizing surgical outcomes in OVFs, tailored surgical techniques are needed. Surgeons need to pay attention to advances in osteoporotic spinal surgery and should be open to novel thoughts and techniques. Prevention and management of osteoporosis is the key element in reducing the risk of subsequent OVFs. Bisphosphonates and teriparatide are mainstay drugs for improving fracture healing in OVF. The effects of bisphosphonates on fracture healing have not been clinically evaluated. The intermittent administration of teriparatide significantly enhanced spinal fusion and fracture healing and reduced mortality risk. Based on the current literature, there is still a lack of standard management strategies for OVF. There is a need for greater efforts through multimodal approaches including conservative treatment, surgery, osteoporosis treatment, and drugs that promote fracture healing to improve the quality of the guidelines.

Intermittent versus continuous enteral nutrition attenuates increases in insulin and leptin during short-term bed rest

PurposeTo compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest.MethodsTwenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n = 10; 24 h day−1 at a constant rate) or intermittent (INTERMITTENT; n = 10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations.ResultsDuring bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42 ± 0.38 vs 0.95 ± 0.48 nmol L−1, respectively; P = 0.014) as were insulin concentrations (interaction effect, P < 0.001) which reached a peak of 369 ± 225 pmol L−1 in CONTINUOUS, compared to 94 ± 38 pmol L−1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r = 0.44, P = 0.049).ConclusionIntermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition.This trial was registered on clinicaltrials.gov as NCT02521025.

Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults After Bed Rest.

Acute bed rest places older adults at risk for health complications by disrupting homeostasis in many organ systems, including the cardiovascular system. Circulating ceramides are emerging biomarkers predictive of cardiovascular and metabolic health and have recently been shown to be sensitive indices of cardiovascular (CV) risk. Therefore, the purpose of this study was to characterize the time course of changes in circulating ceramides in healthy younger and older adults after 5 days of bed rest and to determine whether short-term bed rest alters CV-related circulating ceramides. We hypothesized that circulating ceramides predictive of poor cardiometabolic outcomes would increase following 5 days of bed rest. Thirty-five healthy younger and older men and women (young: n = 13, old: n = 22) underwent 5 days of controlled bed rest. Fasting blood samples collected daily during the course of bed rest were used to measure circulating ceramides, lipoproteins, adiponectin, and fibroblast growth factor 21 (FGF21) levels. The primary findings were that circulating ceramides decreased while ceramide ratios and the cardiac event risk test 1 score were increased primarily in older adults, and these findings were independent of changes in circulating lipoprotein levels. Additionally, we found that changes in circulating adiponectin, FGF21 and the 6-minute walk test (6MW) inversely correlated with CV-related circulating ceramides after bed rest. The results of this study highlight the sensitivity of circulating ceramides to detect potential CV dysfunction that may occur with acute physical disuse in aging.

Changes in muscle power after usual care or early structured exercise intervention in acutely hospitalized older adults

BackgroundA classic consequence of short‐term bed rest in older adults is the significant loss in skeletal muscle mass and muscle strength that underlies the accelerated physical performance deficits. Structured exercise programmes applied during acute hospitalization can prevent muscle function deterioration.MethodsA single‐blind randomized clinical trial conducted in an acute care for elders unit in a tertiary public hospital in Navarre (Spain). Three hundred seventy hospitalized patients [56.5% female patients; mean age (standard deviation) 87.3 (4.9) years] were randomly allocated to an exercise intervention (n = 185) or a control (n = 185) group (usual care). The intervention consisted of a multicomponent exercise training programme performed during 5–7 consecutive days (2 sessions/day). The usual‐care group received habitual hospital care, which included physical rehabilitation when needed. The main endpoints were change in maximal dynamic strength (i.e. leg‐press, chest‐press, and knee extension exercises) and maximal isometric knee extensors and hip flexors strength from baseline to discharge. Changes in muscle power output at submaximal and maximal loads were also measured after the intervention.ResultsThe physical exercise programme provided significant benefits over usual care. At discharge, the exercise group showed a mean increase of 19.6 kg [95% confidence interval (CI), 16.0, 23.2; P < 0.001] on the one‐repetition maximum (1RM) in the leg‐press exercise, 5.7 kg (95% CI, 4.7, 6.8; P < 0.001) on the 1RM in the chest‐press exercise, and 9.4 kg (95% CI, 7.3, 11.5; P < 0.001) on the 1RM in the knee extension exercise over usual‐care group. There were improvements in the intervention group also in the isometric maximal knee extension strength [14.8 Newtons (N); 95% CI, 11.2, 18.5 vs. −7.8 N; 95% CI, −11.0, −3.5 in the control group; P < 0.001] and the hip flexion strength (13.6 N; 95% CI, 10.7, 16.5 vs. −7.2 N; 95% CI, −10.1, −4.3; P < 0.001). Significant benefits were also observed in the exercise group for the muscle power output at submaximal loads (i.e. 30% 1RM, 45% 1RM, 60% 1RM, and 75% 1RM; all P < 0.001) over usual‐care group.ConclusionsAn individualized, multicomponent exercise training programme, with special emphasis on muscle power training, proved to be an effective therapy for improving muscle power output of lower limbs at submaximal loads and maximal muscle strength in older patients during acute hospitalization.

Short-term bed rest-induced insulin resistance cannot be explained by increased mitochondrial H2 O2 emission.

We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance. Bed rest decreased maximal and submaximal ADP-stimulated mitochondrial respiration. Bed rest did not alter mitochondrial H2 O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2 O2 emission to mitochondrial O2 consumption or markers of oxidative stress The present data suggest strongly that mitochondrial H2 O2 does not contribute to bed rest-induced insulin resistance ABSTRACT: Mitochondrial H2 O2 has been causally linked to diet-induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H2 O2 . Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H2 O2 emission, potentially as a result of decreased ADP sensitivity, contributes to cellular redox stress and the induction of insulin resistance during short-term bed rest in 20 healthy males. Bed rest led to a decline in glucose infusion rate during a hyperinsulinaemic-euglycaemic clamp (-42±2%; P<0.001), and in permeabilized skeletal muscle fibres it decreased OXPHOS protein content (-16±8%) and mitochondrial respiration across a range of ADP concentrations (-13±5%). While bed rest tended to increase maximal mitochondrial H2 O2 emission rates (P=0.053), H2 O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2 O2 emission to mitochondrial O2 consumption, and markers of oxidative stress were not altered following bed rest. Altogether, while bed rest impairs mitochondrial ADP-stimulated respiration, an increase in mitochondrial H2 O2 emission does not contribute to the induction of insulin resistance following short-term bed rest.

Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest.

Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may have an impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25 ± 1 yr, body mass index: 23.8 ± 0.8 kg/m2) to 1 wk of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days before bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (dual energy X-ray absorptiometry), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (V̇o2peak), and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Muscle biopsies were collected 7 days before, 1 day before, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3 ± 0.3 vs. 0.7 ± 0.4 kg lean tissue loss and a 1.1 ± 0.6 vs. 0.8 ± 0.5% decline in quadriceps CSA in the intermittent vs. continuous feeding group, respectively (both P < 0.05), with no differences between groups (both P > 0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46 ± 3% vs. 39 ± 3%; P < 0.001) or V̇o2peak (-2.5 ± 2.2 vs. -8.6 ± 2.2%; P < 0.010) (both P > 0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33 ± 0.07 vs. 1.50 ± 0.13%/day, respectively; P > 0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during 1 wk of bed rest in healthy men.

Utilizing Next Generation Sequencing to Describe Age-Related Skeletal Muscle Changes with Bed Rest

Short-term bed rest is used to simulate periods of disuse experienced during hospital visitation. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects (Interaction: P < 0.001). Identifying muscle transcriptional events that underlie this consequence of bed rest will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. PURPOSE: To compare the gene transcriptome response between YOUNG and OLD skeletal muscle after bed rest and identify a transcriptional program that underlies rapid loss of muscle mass. METHODS: RNA was isolated and sequenced (HiSeq, Illumina; DESeq, R) from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9; 22.9 ± 1.1 y, 171.6 ± 2.0 cm, 65.6 ± 4.6 kg) and OLD (N=18; 67.6 ± 1.3 y, 173.7 ± 1.8 cm, 75.7 ± 2.2 kg) men and women before and after five days of bed rest (Tanner et al 2015; Reidy et al 2017). RESULTS: After bed rest, 551 genes responded similarly and 61 genes were differentially regulated between YOUNG and OLD (P < 0.05). Ingenuity Pathway Analysis identified the top commonly regulated pathways to be related to Actin Cytoskeleton Signaling, ILK Signaling, Calcium Signaling, and Mitochondrial Dysfunction. Out of the differentially regulated genes, 51 were altered in YOUNG (42 increased, 9 decreased) but were unresponsive in OLD after bed rest (P < 0.05). On the other hand, 9 genes were altered only in OLD as a result of bed rest (P < 0.05) of which 5 are protein coding (MRPL49, HIST1H2BC: increased; PXDNL, NEXN, MAGI2: decreased). These genes code for proteins related to mitochondrial function, DNA structure, oxidative stress, Z-disc stabilization, and activin signaling, respectively. CONCLUSION: Our preliminary results indicate that altered gene expression in YOUNG in response to bed rest may be indicative of a compensatory expression profile to combat muscle loss. Additional investigation of the differentially regulated gene responses in young and old adults are ongoing in efforts to further describe underlying molecular events that occur in response to bed rest. Supported by NIH Grant R01 AG050781.

PERSONALIZED EXERCISE TRAINING PROGRAM AS A COUNTERMEASURE TO ORTHOSTATIC INTOLERANCE AFTER SPACE FLIGHTS.

PERSONALIZED EXERCISE TRAINING PROGRAM AS A COUNTERMEASURE TO ORTHOSTATIC INTOLERANCE AFTER SPACE FLIGHTS.

Combined effects of physical inactivity and acute hyperglycemia on arterial distensibility.

Arterial distensibility, an independent predictor of cardiovascular events, is transiently increased with acute hyperglycemia (AHG) in healthy individuals. Whether this response interacts with physical inactivity remains unknown. We examined the effects of short-term bed rest (BR) on the response of carotid artery distensibility (CD) to AHG, and the influence of underlying changes in insulin resistance and blood volume. CD was assessed with ultrasonography before as well as 30 and 120 minutes following ingestion of 75 g of glucose prior to and after 3 days of BR in 15 healthy male volunteers. Plasma insulin/glucose concentrations and blood volumes were concomitantly determined. On day 4 of BR, blood volume was re-established to pre-BR levels by albumin infusion and CD and insulin/glucose concentrations were determined as in the previous experimental days. Basal CD was not affected by BR. AHG increased CD before and after BR but reached a higher peak increment after BR (12% vs 60% at 30 min OGTT, p=0.028). BR also increased the plasma insulin concentration during AHG ( p=0.007). In regression analyses, plasma insulin and glucose concentrations were positively correlated to CD, particularly after BR ( r=0.31, p<0.05). Restoration of the BR-induced loss (5%) in blood volume did not affect the response of CD to AHG. In conclusion, short-term physical inactivity strongly accentuates the initial increase in CD in response to AHG in healthy individuals. This effect is associated with concomitant increases in circulating insulin concentration attributable to early insulin resistance.

Neuromuscular Electrical Stimulation Combined with Protein Ingestion Preserves Thigh Muscle Mass But Not Muscle Function in Healthy Older Adults During 5 Days of Bed Rest.

Short-term bed rest in older adults is characterized by significant loss in leg lean mass and strength posing significant health consequences. The purpose of this study was to determine in healthy older adults if the daily combination of neuromuscular electrical stimulation and protein supplementation (NMES+PRO) would protect muscle mass and function after 5 days of bed rest. Twenty healthy older adults (∼70 years) were subjected to 5 days of continuous bed rest and were randomized into one of two groups: NMES+PRO (n = 10) or control (CON) (n = 10). The NMES+PRO group received bilateral NMES to quadriceps (40 minutes/session, 3 × /day; morning, afternoon, and evening) followed by an interventional protein supplement (17 g). The CON group received an isocaloric equivalent beverage. Before and after bed rest, vastus lateralis biopsies occurred before and after acute essential amino acid (EAA) ingestion for purposes of acutely stimulating mechanistic target of rapamycin (mTORC1) signaling, a major regulator of muscle protein synthesis, in response to bed rest and NMES+PRO. Baseline (pre and post bed rest) muscle samples were also used to assess myofiber characteristics and gene expression of muscle atrophy markers. Thigh lean mass and muscle function were measured before and after bed rest. Five days of bed rest reduced thigh lean mass, muscle function, myofiber cross-sectional area, satellite cell content, blunted EAA-induced mTORC1 signaling, and increased myostatin and MAFbx mRNA expression. Interestingly, NMES+PRO during bed rest maintained thigh lean mass, but not muscle function. Thigh muscle preservation during bed rest with NMES+PRO may partly be explained by attenuation of myostatin and MAFbx mRNA expression rather than restoration of nutrient-induced mTORC1 signaling. We conclude that the combination of NMES and protein supplementation thrice a day may be an effective therapeutic tool to use to preserve thigh muscle mass during periods of short-term hospitalization in older adults. However this combined intervention was not effective to prevent the loss in muscle function.

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions.Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA.Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients.

The ability of low-magnitude mechanical signals to normalize bone turnover in adolescents hospitalized for anorexia nervosa.

Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN. In this randomized, double-blind trial, we prospectively enrolled adolescent females (n=41) with AN, age 16.3±1.9years (mean±SD) and BMI 15.6±1.7kg/m2. Participants were randomized to stand on a platform delivering LMMS (0.3g at 32-37Hz) or placebo platform for 10min/day for 5days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes. BSAP decreased by 2.8% per day in the placebo arm (p=0.03) but remained stable in the LMMS group (p=0.51, pdiff=0.04). CTx did not change with placebo (p=0.56) but increased in the LMMS arm (+6.2% per day, p=0.04; pdiff=0.01). Serum OC did not change in either group (p>0.70). Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.