Days Of Bed Rest Research Articles

Anticoagulation management in gynecologic brachytherapy patients with perioperative or chronic thromboembolic disease: A retrospective analysis

Women on chronic anticoagulation (AC) who require operative brachytherapy for gynecologic malignancies represent a clinical challenge, but no guidelines exist regarding patient selection for brachytherapy or their perioperative management. We aimed to understand the incidence of hemorrhagic and embolic events in our patients on chronic AC and suggest management strategies for this patient population. A retrospective, single institutional study of patients treated with operative, gynecologic brachytherapy from 2013 to 2023 was performed to identify patients on chronic AC. We determined indications for AC use, oncologic therapy characteristics, duration of AC interruption, and therapy outcomes. The primary aim was to determine perioperative embolic or hemorrhagic complications as measured by the Common Terminology Criteria for Adverse Events. Of 304 patients treated with operative implants, 32 (10%) were on chronic AC for venous thromboembolism (n = 25), or atrial fibrillation/flutter (n = 13). The most common malignancies were cervical (n = 15) and inoperable uterine (n = 11). Implants were intracavitary (n = 14), interstitial (n = 6), or hybrid (n = 12) with a median (range) of 2 (1-3) implants, 4 (2-5) fractions, and 2 (1-3) days of bedrest per implant. 63% (n = 20) had an epidural for analgesia. AC was held for a median 3 days in 94% (n = 30) prior to the operative implant, and pharmacologic DVT prophylaxis was used in 78% (n = 25). There were two grade ≥ 2 hemorrhagic events and no new embolic events. The rate of bleeding and embolic events was acceptable, and women on chronic AC should not be excluded from potentially lifesaving operative brachytherapy, including complex cases that require spinal analgesia and interstitial applicators.

Key Anabolic Markers in Human M. Soleus after 21-Day Head-Down Tilt Bedrest

Prolonged bed rest can have a significant negative effect on skeletal muscle, leading to muscle wasting and reduced strength. This process can occur in as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDT) is a method used to simulate the physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. This paper is dedicated to the analysis of key anabolic markers of the soleus muscle during 21 days of HDT BR. The HDT BR experiment was conducted at the Institute of Biomedical Problems, Russian Academy of Sciences. Six healthy male volunteers, aged 25–35 years, were subjected to 21 days of strict bed rest with a tilt angle of –6°. A needle biopsy of the m.soleus was performed using the Bergström method before the start of HDT BR and on day 21 of HDT BR. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. Examination of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDT BR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDT BR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDT BR.

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.

Title: Influence of the NASA SPRINT exercise protocol on myonuclear and satellite cell content of the vastus lateralis and soleus during 70 days of bedrest

Objectives: The purpose of this study was to assess the effcacy of the NASA SPRINT exercise protocol in preserving myonuclear and satellite cell number of the quadriceps (vastus lateralis) and triceps surae (soleus) muscles following 70 days of bedrest (i.e., simulated microgravity). These two muscles were the focus of this study because they both atrophy significantly with microgravity exposure in the absence of countermeasures. Hypotheses: The SPRINT exercise protocol will preserve myonuclear number (MNN), myonuclear domain (MND), and satellite cell number (SCN) during 70 days of bedrest. Methods: Subjects were randomized into three groups: bedrest only (BR; n=8, 37±3 y), bedrest with endurance and resistance exercise (BRE; n=9, 34±2 y) and bedrest with endurance and resistance exercise and low dose testosterone injections (BRE+T; n=8, 33±3 y). Muscle biopsies were taken before and at the end of bedrest from the vastus lateralis and soleus, and were sectioned, immunofluorescently stained, and analyzed for MNN (myonuclei/fiber), MND (μm2/myonuclei), and SCN (satellite cells/fiber) in slow (myosin heavy chain (MHC) I) and fast (MHC IIa) muscle fibers. SCN was only determined in MHC I fibers for the soleus. Results: MNN, MND, and SCN in MHC I and IIa fibers of the vastus lateralis and soleus were unchanged (p<0.05) from pre- to post-bedrest within BR, BRE, and BRE+T. However, there was a main effect for time (p<0.05) for a decrease in MND for vastus lateralis MHC I fibers (-8%), as well as soleus MHC I (-18%) and IIa (-18%) fibers. Also, there was a trend for a main effect for time (P=0.059) for an increase (+37%) in SCN for vastus lateralis MHC IIa fibers, which was driven primarily by the exercise groups (BR: -4%, BRE: +36%, BRE+T: +67%). Conclusions: Myonuclear number appears to be unaltered during 70 days of simulated microgravity with or without countermeasures exercise. As a result, any changes in myonuclear domain correspond with alterations in muscle mass. Satellite cell number also appears to be relatively refractory to change, but may be influenced in fast muscle fibers under the combined dynamic cellular control mechanisms of exercise and atrophy encountered during relatively long-duration simulated microgravity. Funding Source: This research was supported by the National Aeronautics and Space Administration, NNJ06HF59G; the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UR1TR000071) from the National Center for Advancing Translational Sciences, National Institutes of Health; the NASA Flight Analogs Project; and the Human Bioenergetic Program at Ball State University. 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.

Metformin Blunts Bed Rest-induced Skeletal Muscle Ceramide Accumulation in Older Adults

Skeletal muscle insulin resistance is an undesirable outcome during periods of physical inactivity in older adults, which can lead to a variety of metabolic diseases. Insulin sensitive tissue (e.g., liver, and skeletal muscle) derived ceramides are well known to promote insulin resistance. Evidence suggests that metformin can regulate tissue ceramide accumulation. Therefore, we hypothesized that metformin treatment during a short-term period of bed rest in male and female older adults would reduce skeletal muscle ceramide accumulation and prevent insulin resistance. Our study design consisted of older adults (66 ± 4.5 y/o placebo, n=10; 71.7 ± 5.1 y/o metformin, n=10) who were subjected to 5 days of bed rest. Participants were randomly assigned to placebo or metformin treatment groups. Drug or placebo treatments started two weeks prior to bed rest and continued throughout the 5 days of bed rest. Prior to and after bed rest, participants underwent a euglycemic-hyperinsulinemic clamp. Muscle biopsies (from the vastus lateralis) were taken prior to and after each clamp both before and after bed rest. We found that insulin-stimulated muscle ceramides were increased after bed rest but were blunted in older adults who took metformin. In addition, muscle insulin resistance correlated with the increase in ceramides. We conclude that metformin was effective to reduce ceramide accumulation in muscle during a period of bed rest in older adults. R21AG064576 awarded to M.J.D. 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.

Effect of 60 days of head down tilt bed rest on amplitude and phase of rhythms in physiology and sleep in men

Twenty-four-hour rhythms in physiology and behaviour are shaped by circadian clocks, environmental rhythms, and feedback of behavioural rhythms onto physiology. In space, 24 h signals such as those associated with the light-dark cycle and changes in posture, are weaker, potentially reducing the robustness of rhythms. Head down tilt (HDT) bed rest is commonly used to simulate effects of microgravity but how HDT affects rhythms in physiology has not been extensively investigated. Here we report effects of −6° HDT during a 90-day protocol on 24 h rhythmicity in 20 men. During HDT, amplitude of light, motor activity, and wrist-temperature rhythms were reduced, evening melatonin was elevated, while cortisol was not affected during HDT, but was higher in the morning during recovery when compared to last session of HDT. During recovery from HDT, time in Slow-Wave Sleep increased. EEG activity in alpha and beta frequencies increased during NREM and REM sleep. These results highlight the profound effects of head-down-tilt-bed-rest on 24 h rhythmicity.

Lessons from an elderly patient with pulmonary embolism caused by protein S deficiency: a case report

BackgroundLower limb deep vein thrombosis (DVT) concurrent with pulmonary embolism (PE) is perilous, particularly in the elderly, exhibiting heterogeneity with thrombophilia mutations. Tailored treatment is essential, yet sudden deaths complicate causative factor elucidation. This report emphasizes genetic testing necessity in PE patients with thrombophilia indicators, facilitating cause identification, personalized treatment guidance, and family education.Case presentationThis study details a 75-year-old Chinese woman with DVT and PE, where genetic testing identified thrombophilia, guiding personalized treatment decisions.ResultsUpon admission, the patient, after over 10 days of bed rest, presented chest tightness, shortness of breath, and unilateral leg swelling. Diagnostic measures revealed DVT and a substantial PE. Genetic testing identified a PROS1 gene C200A>C mutation, reducing protein S activity. Following 2 weeks of anticoagulation and inferior vena cava filter insertion, the patient, discharged, initiated lifelong anticoagulant therapy. A 1-year follow-up showed no recurrent thrombotic events. Family members carrying the mutation received informed and educational interventions.ConclusionGenetic testing for thrombophilic predisposition post-PE is crucial, elucidating etiology, guiding individualized treatment, and playing a pivotal role in family education.

Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

Changes in real-world walking speed following 60-day bed-rest

The aim of this work was to explore whether real-world walking speed (RWS) would change as a consequence of 60-day bed-rest. The main hypothesis was that daily RWS would decrease after the bed-rest, with a subsequent recovery during the first days of re-ambulation. Moreover, an exploratory analysis was done in order to understand whether there is an agreement between the loss in RWS after bed-rest and the loss in the maximum oxygen uptake capacity (VO2max), or the loss in maximal vertical jump power (JUMP) respectively. Twenty-four subjects were randomly assigned to one of three groups: a continuous artificial gravity group, an intermittent artificial gravity group, or a control group. The fitted linear mixed effects model showed a significant decrease (p < 0.001) of RWS after the 60-day bed-rest and a subsequent increase (p < 0.001) of RWS during the 14-day recovery period in the study facility. No or little agreement was found between the loss in RWS and the loss in VO2max capacity or the loss in maximal vertical jumping power (RWS vs. VO2max: p = 0.81, RWS vs. JUMP: p = 0.173). Decreased RWS after bed-rest, with a follow-up recovery was observed for all three groups, regardless of the training intervention. This suggests that RWS, also in these settings, was able to reflect a de-conditioning and follow-up recovery process.

Immobilization by 21 days of bed rest results in type II collagen degradation in healthy individuals

To investigate the effects of 21 days of bed rest immobilization (with and without exercise and nutrition interventions) on type II collagen biomarker concentrations in healthy individuals. Twelve healthy male participants (age 34.2±8.3years; body mass index 22.4±1.7kg/m²) were exposed to 6days ambulatory baseline data collection (BDC), 21days head-down-tilt bed rest (HDT, CON)+interventions (HDT+resistive vibration exercise (2 times/week, 25minutes): RVE; HDT+RVE+whey protein (0.6g/kg body weight/day) and bicarbonate supplementation (90mmol KHCO3/day: NeX), and 6days of re-ambulation (R) in a cross-over designed study. The starting HDT condition was randomized (CON-RVE-NEX, RVE-NEX-CON, NEX-CON-RVE). Blood and urine samples were collected before, during, and after HDT. Serum concentrations (s) of CPII, C2C, C1,2C, and urinary concentrations (u) of CTX-II and Coll2-1NO2 were measured. Twenty-one days of HDT resulted in increased sCPII (p < 0.001), sC2C (p < 0.001), and sC1,2C (p=0.001) (highest increases: sCPII (+24.2% - HDT5), sC2C (+24.4% - HDT7), sC1,2C (+13.5% - HDT2). sC2C remained elevated at R+1 (p=0.002) and R+6 (p < 0.001) compared to baseline. NeX led to lower sCPII (p < 0.001) and sC1,2C (p = 0.003) compared to CON. uCTX-II (second void and 24-hour urine) increased during HDT (p < 0.001, highest increase on HDT21: second void +82.8% (p < 0.001); 24-hour urine+77.8% (p < 0.001). NeX resulted in lower uCTX-II concentrations in 24-hour urine (p = 0.012) compared to CON. Twenty-one days of bed rest immobilization results in type II collagen degradation that does not recover within 6days of resuming ambulation. The combination of resistive vibration exercise and protein/bicarbonate supplementation minimally counteracted this effect.

Retinal venular vessel diameters are smaller during ten days of bed rest

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m–2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Microgravity-induced skeletal muscle atrophy in women and men: implications for long-duration spaceflights to the Moon and Mars.

The inclusion of women on spaceflights has historically been limited. Recently, the first woman who will travel to the Moon was selected, and more women are participating in long-duration spaceflights. However, physiological data from real and simulated microgravity exposure are limited in women. This investigation studied women (n = 8, 34 ± 1 yr) and men (n = 9, 32 ± 1 yr) who underwent 2 (women) or 3 (men) mo of simulated microgravity (6° head-down tilt bed rest). Quadriceps and triceps surae muscle volumes were assessed via MRI before bed rest, bed rest day 29 (BR29, women and men), bed rest day 57 (BR57, women), and bed rest day 89 (BR89, men). Volume of both muscle groups decreased (P < 0.05) in women and men at all bed rest timepoints. Quadriceps muscle volume loss in women was greater than men at 1 mo (BR29: -17% vs. -10%, P < 0.05) and this 1-mo loss for women was similar to men at 3 mo (BR89: -18%, P > 0.05). In addition, the loss in women at 2 mo (BR57: -21%) exceeded men at 3 mo (P < 0.05). For the triceps surae, there was a trend for greater muscle volume loss in women compared with men at 1 mo (BR29: -18% vs. -16%, P = 0.08), and loss in women at 2 mo was similar to men at 3 mo (BR57: -29%, BR89: -29%, P > 0.05). The collective evidence suggests that women experience greater lower limb muscle atrophy than men at least through the first 4 mo of microgravity exposure. More sex-specific microgravity studies are needed to help protect the health of women traveling on long-duration orbital and interplanetary spaceflights.NEW & NOTEWORTHY This study adds to the limited evidence regarding sex-specific responses to real or simulated microgravity exposure, which collectively suggests a sex-specific muscle atrophy profile, with women losing more than men at least through the first 4 mo of weightlessness. Considering the increase in women being selected for space missions, including the first women to travel to the Moon, more physiological data on women in response to microgravity are needed.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures

Introduction: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. Methods: Twenty-three participants (12 males and 11 females), aged 55–65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. Results: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. Conclusion: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Longitudinal Changes in Cerebral Perfusion, Perivascular Space Volume, and Ventricular Volume in a Healthy Cohort Undergoing a Spaceflight Analog.

A global decrease in brain perfusion has recently been reported during exposure to a ground-based spaceflight analog. Considering that CSF and glymphatic flow are hypothesized to be propelled by arterial pulsations, it is unknown whether a change in perfusion would impact these CSF compartments. The aim of the current study was to evaluate the relationship among changes in cerebral perfusion, ventricular volume, and perivascular space volume before, during, and after a spaceflight analog. Eleven healthy participants underwent 30 days of bed rest at 6° head-down tilt with 0.5% atmospheric CO2 as a spaceflight analog. For each participant, 6 MR imaging brain scans, including perfusion and anatomic-weighted T1 sequences, were obtained before, during, and after the analog period. Global perfusion, ventricular volume, and perivascular space volume time courses were constructed and evaluated with repeated measures ANOVAs. Global perfusion followed a divergent time trajectory from ventricular and perivascular space volume, with perfusion decreasing during the analog, whereas ventricular and perivascular space volume increased (P < .001). These patterns subsequently reversed during the 2-week recovery period. The patterns of change in brain physiology observed in healthy participants suggest a relationship between cerebral perfusion and CSF homeostasis. Further study is warranted to determine whether a causal relationship exists and whether similar neurophysiologic responses occur during spaceflight.

EARLY MOBILIZATION AND THE ELASTIC BAND, AN EFFICIENT SOLUTION FOR AN INTUBATED SUBJECT: A CASE STUDY

ABSTRACT. Introduction: In severely ill patients, weakness acquired in the intensive care unit is a frequent consequence. The advantages of early mobilization for adult intensive care unit patients include shorter stays in the intensive care unit and hospitals, a shorter need for mechanical ventilation, fewer days of harmful bedrest, fewer negative or dangerous occurrences, and increased walking distance. Early mobilization and rehabilitation programs using elastic bands for patients with severe illnesses in intensive care units enhance the weaning success and shorten ventilation times while also enhancing arm muscular power. Objective: This study case aimed to present the fact that early mobilization and elastic band exercises were efficient solutions for an intubated subject from the intensive care unit. Methods: A mechanically ventilated subject postoperatively for hiatal hernia and suspected phrenic nerve paresis, benefited from early mobilization and elastic band exercises and was assessed for the state of consciousness with the Richmond Agitation Scale, and muscle strength for the upper limb with the EH101 digital dynamometer. Results: Muscle strength at the level of the upper limbs increased from weak to normal and the subject was successfully extubated. Conclusions: In this case study we consider that early mobilization and the elastic band exercises program were effective, safe, inexpensive, and suitable for an intensive care unit, and it was the right solution for the success of weaning from the ventilator.

Effects of Posture and Walking on Tibial Vascular Hemodynamics Before and After 14 Days of Head-Down Bed Rest.

Human skeletal hemodynamics remain understudied. Neither assessments in weight-bearing bones during walking nor following periods of immobility exist, despite knowledge of altered nutrient-artery characteristics after short-duration unloading in rodents. We studied 12 older adults (8 females, aged 59 ± 3 years) who participated in ambulatory near-infrared spectroscopy (NIRS) assessments of tibial hemodynamics before (PRE) and after (POST) 14 days of head-down bed rest (HDBR), with most performing daily resistance and aerobic exercise countermeasures during HDBR. Continual simultaneous NIRS recordings were acquired over the proximal anteromedial tibial prominence of the right lower leg and ipsilateral lateral head of the gastrocnemius muscle during supine rest, walking, and standing. During 10 minutes of walking, desaturation kinetics in the tibia were slower (time to 95% nadir values 125.4 ± 56.8 s versus 55.0 ± 30.1 s, p = 0.0014). Tibial tissue saturation index (TSI) immediately fell (-9.9 ± 4.55) and did not completely recover by the end of 10 minutes of walking (-7.4 ± 6.7%, p = 0.027). Upon standing, total hemoglobin (tHb) kinetics were faster in the tibia (p < 0.0001), whereas HDBR resulted in faster oxygenated hemoglogin (O2Hb) kinetics in both tissues (p = 0.039). After the walk-to-stand transition, changes in O2Hb (p = 0.0022) and tHb (p = 0.0047) were attenuated in the tibia alone after bed rest. Comparisons of NIRS-derived variables during ambulation and changes in posture revealed potentially deleterious adaptations of feed vessels after HDBR. We identify important and novel tibial hemodynamics in humans during ambulation before and after bed rest, necessitating further investigation. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cardiovascular responses to daily use of lower body negative pressure during 30 days of strict head-down tilt bedrest

Introduction: Exposure to weightlessness causes a chronic headward fluid shift that is believed to underlie numerous risks associated with spaceflight, including the development of cephalad venous congestion, venous thromboembolism, and Spaceflight Associated Neuro-ocular Syndrome (SANS). Application of moderate levels (25 mmHg) of lower body negative pressure (LBNP) during spaceflight can partially reverse the headward fluid shift, and thus, may represent a promising countermeasure. Strict head-down tilt bed rest (HDTBR), a spaceflight analog, causes the development of some SANS findings and is used as a platform to test candidate countermeasures. Purpose: To measure the heart rate (HR) and mean arterial pressure (MAP) response during and subject tolerance to twice daily use of 3 hours of 25 mmHg LBNP during 30 days of HDTBR. Hypothesis: We hypothesized that during 3 hours of moderate LBNP MAP would be maintained, but HR would increase and that these responses would not be altered throughout 30 days of HDTBR. Methods: Twelve subjects (n = 12; 6 female) maintained strict 6˚ HDTBR for 30 days (HDT1 through HDT30) and were exposed to 2 separate 3-hour sessions of LBNP with continuous blood pressure and HR monitoring (Finapres, NOVA). Continuous data were averaged across 10-minute segments during each 3-hour LBNP period for statistical analyses to determine if MAP or HR changed within the 3-hour LBNP exposure, and whether the response to LBNP changed across all study days. Data were analyzed with generalized linear models with GEE effects to address repeated measures within subjects. Time trends over the 3 hours were modeled by the best fitting model utilizing linear or natural cubic splines of time. Results: All LBNP sessions (720 total) were completed across the 30 days of strict HDTBR, and no sessions were terminated early. In the first 10 minutes of LBNP MAP increased (+4 mmHg, p&lt;0.01) and increased further over time (additional +3 mmHg by the final 10 minutes of LBNP exposure, p=0.02). This response did not change over the 30 days of HDTBR (p=0.67). Similarly, HR increased (+7 bpm, p&lt;0.01) during the first 10 minutes of LBNP exposure but decreased towards pre-LBNP levels by the conclusion of LBNP (-6 bpm, p&lt;0.0001). The HR response to LBNP did not change over 30 days of HDTBR (p=0.14). Conclusion: Twice daily use of 25 mmHg LBNP during 30 days of strict HDTBR was well-tolerated with no reported hypotensive symptoms or cardiovascular responses suggestive of impending syncope. Despite cardiovascular deconditioning expected to occur due to inactivity during HDTBR, neither the MAP or HR response to LBNP were significantly changed between HDT1 and HDT30. Prolonged use of moderate LBNP should be further investigated as a potential countermeasure for various risks associated with long-duration spaceflight. National Aeronautics and Space Administration Human Research Program Directed Research This is the full abstract presented at the American Physiology Summit 2023 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.

The Role of Prolonged Bed Rest in Postoperative Cerebrospinal Fluid Leakage After Surgery of Intradural Pathology-A Retrospective Cohort Study.

Postoperative cerebrospinal fluid leakage (CSFL) is a feared complication after surgery on intradural pathologies and may cause postoperative complications and subsequently higher treatment costs. To assess whether prolonged bed rest may lower the risk of CSFL. We performed a retrospective cohort study including patients with intradural pathologies who underwent surgery at our department between 2013 and 2021. Cohorts included patients who completed 3 days of postoperative bed rest and patients who were mobilized earlier. The primary end point was the occurrence of clinically proven CSFL. Four hundred and thirty-three patients were included (female [51.7%], male [48.3%]) with a mean age of 48 years (SD ±20). Bed rest was ordered in 315 cases (72.7%). In 7 cases (N = 7/433, 1.6%), we identified a postoperative CSFL. Four of them (N = 4/118) did not preserve bed rest, showing no significant difference to the bed rest cohort (N = 3/315; P = .091). In univariate analysis, laminectomy (N = 4/61; odds ratio [OR] 8.632, 95% CI 1.883-39.573), expansion duraplasty (N = 6/70; OR 33.938, 95% CI 4.019-286.615), and recurrent surgery (N = 5/66; OR 14.959, 95% CI 2.838-78.838) were significant risk factors for developing CSFL. In multivariate analysis, expansion duraplasty was confirmed as independent risk factor (OR 33.937, 95% CI 4.018-286.615, P = .001). In addition, patients with CSFL had significant higher risk for meningitis (N = 3/7; 42.8%, P = .001). Prolonged bed rest did not protect patients from developing CSFL after surgery on intradural pathologies. Avoiding laminectomy, large voids, and minimal invasive approaches may play a role in preventing CSFL. Furthermore, special caution is indicated if expansion duraplasty was done.

The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males

It is unclear if dietary adjustments to maintain energy balance during reduced physical activity can offset inactivity-induced reductions in insulin sensitivity and glucose disposal to produce normal daily glucose concentrations and meal responses. Therefore, the aim of the present study was to examine the impact of long-term physical inactivity (60 days of bed rest) on daily glycemia when in energy balance. Interstitial glucose concentrations were measured using Continuous Glucose Monitoring Systems (CGMS) for 5 days before and towards the end of bed rest in 20 healthy, young males (Age: 34±8 years; BMI: 23.5±1.8kg/m2). Energy intake was reduced during bed rest to match energy expenditure, but the types of foods and timing of meals was maintained. Fasting venous glucose and insulin concentrations were determined, as well as the change in whole-body glucose disposal using a hyperinsulinemic-euglycemic clamp (HIEC). Following long-term bed rest, fasting plasma insulin concentration increased 40% (p=0.004) and glucose disposal during the HIEC decreased 24% (p<0.001). Interstitial daily glucose total area under the curve (tAUC) from pre-to post-bed rest increased on average by 6% (p=0.041), despite a 20 and 25% reduction in total caloric and carbohydrate intake, respectively. The nocturnal period (00:00-06:00) showed the greatest change to glycemia with glucose tAUC for this period increasing by 9% (p=0.005). CGMS measures of daily glycemic variability (SD, J-Index, M-value and MAG) were not changed during bed rest. Reduced physical activity (bed rest) increases glycemia even when daily energy intake is reduced to maintain energy balance. However, the disturbance to daily glucose homeostasis was much more modest than the reduced capacity to dispose of glucose, and glycemic variability was not negatively affected by bed rest, likely due to positive mitigating effects from the contemporaneous reduction in dietary energy and carbohydrate intake. NCT03594799 (registered July 20, 2018) (https://clinicaltrials.gov/ct2/show/NCT03594799).

ЭКСПРЕССИЯ E3-УБИКВИТИНЛИГАЗ MuRF-1 И MAFbx В ПОСТУРАЛЬНОЙ И ЛОКОМОТОРНОЙ МЫШЦАХ ЧЕЛОВЕКА ПРИ АНТИОРТОСТАТИЧЕСКОЙ ГИПОКИНЕЗИИ

Functional unloading of skeletal muscles enhances proteasome degradation in which the key role is played by Е3-ligases atrogin-1/MAFbx and MuRF-1. Their expression starts growing on the first day of unloading. There is actually little literature on expression of ubiquitin ligases in dry immersion or bedrest. Our purpose was to investigate MuRF-1 and MAFbx expression and control in postural m. soleus and locomotor m. vastus lateralis during a 21-day bedrest study. The observed reduction of cross-section areas in slow fibers of m. soleus and m. vastus lateralis was accompanied by activation of MuRF-1 and MAFbx in m. soleus and MAFbx in m. vastus lateralis, respectively. The investigation of E3 ligases signal pathways showed an increased expression of myogenin and IL-6 receptors in both muscles, whereas transcriptional activation of FoxO3 was seen in m. soleus only. These results suggest elevated expression of Е3-ubiquitin ligases MuRF-1 and MAFbx in m. soleus and MAFbx in m. vastus lateralis, as well as their key signal pathways in bedrested human subjects. Also, our findings argue against the previously stated notion that degradation of protein has no influence on skeletal muscles atrophy due to hypokinesia.