Myths and Methodologies: Understanding the health impact of head down bedrest for the benefit of older adults and astronauts. Study protocol of the Canadian Bedrest Study.

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest.

Elevated biomarkers of neural injury in older adults following head-down bed rest: links to cardio-postural deconditioning with spaceflight and aging.

Introduction: Prolonged physical inactivity with bed rest or spaceflight is associated with cardiovascular and neuromuscular deconditioning; however, its impact on neural integrity of cardio-postural reflexes and possible mitigation with exercise has not been examined. We assessed the association between the physiological deconditioning of bed rest immobilization with neural injury markers and the effects of 60-75 min of daily exercise. Methods: Data were collected as part of a randomized clinical trial (clinicaltrials.gov identifier: NCT04964999) at the McGill University Medical Centre. Twenty-two 55- to 65-year-old healthy volunteers gave informed consent and took part. Within sex, participants were randomly assigned to exercise (60- to 75-min daily) or control (inactive) groups and spent 14 days in continuous 6° head-down tilt. Neural injury [neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-Tau), myelin basic protein (MBP), brain-derived neurotrophic factor (BDNF), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)], as well as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and insulin-like growth factor 1 (IGF-1) biomarkers were measured before, during, and after bed rest. The false discovery rate with Huber M-estimation was used to correlate changes in biomarkers with cardiovascular and muscular function changes over bed rest. Results: Bed rest elevated NfL, GFAP, TNF-α, and IL-6 in all participants and reduced IGF-1 in females only. With standing, changes in heart rate, blood pressure, and lower limb muscle motoneuron activity correlated with changes in TNF-α and BDNF. Baroreflex control, leg muscle maximal voluntary contraction, and postural sway are correlated with GFAP and NfL. Exercise participants had fewer interactions than control participants, but significant correlations still existed, with both groups exhibiting similar reductions in orthostatic tolerance. Discussion: An hour of daily exercise in older persons otherwise immobilized for 2 weeks did not abate bed rest-induced increases in serum signatures of neural injury or pro-inflammatory markers. Exercise reduced the number of physiological interactions of biomarkers, but significant cardio-postural correlations remained with no protection against post-bed rest orthostatic intolerance. The identification of associations of inflammatory and neural injury biomarkers with changes in cardio-postural physiology and exercise points to biotherapeutic opportunities and improved exercise interventions for astronauts and individuals in bed rest. Clinical trial registration: https://www.clinicaltrials.gov/search?cond=NCT04964999, identifier: NCT04964999.

The Effect of Skeletal Muscle-Pump on Blood Pressure and Postural Control in Parkinson's Disease.

PURPOSE: Activation of the calf (gastrocnemius and soleus) and tibialis anterior muscles play an important role in blood pressure regulation (via muscle-pump mechanism) and postural control. Parkinson's disease is associated with calf (and tibialis anterior muscles weakness and stiffness, which contribute to postural instability and associated falls. In this work, we studied the role of the medial and lateral gastrocnemius, tibialis anterior, and soleus muscle contractions in maintaining blood pressure and postural stability in Parkinson's patients and healthy controls during standing. In addition, we investigated whether the activation of the calf and tibialis anterior muscles is baroreflex dependent or postural-mediated. METHODS: We recorded electrocardiogram, blood pressure, center of pressure as a measure of postural sway, and muscle activity from the medial and lateral gastrocnemius, tibialis anterior, and soleus muscles from twenty-six Parkinson's patients and eighteen sex and age-matched healthy controls during standing and with eyes open. The interaction and bidirectional causalities between the cardiovascular, musculoskeletal, and postural variables were studied using wavelet transform coherence and convergent cross-mapping techniques, respectively. RESULTS: Parkinson's patients experienced a higher postural sway and demonstrated mechanical muscle-pump dysfunction of all individual leg muscles, all of which contribute to postural instability. Moreover, our results showed that coupling between the cardiovascular, musculoskeletal, and postural variables is affected by Parkinson's disease while the contribution of the calf and tibialis anterior muscles is greater for blood pressure regulation than postural sway. CONCLUSION: The outcomes of this study could assist in the development of appropriate physical exercise programs that target lower limb muscles to improve the muscle-pump function and reduce postural instability in Parkinson's disease.

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.

Cardio-respiratory interactions in response to lower-body negative pressure.

The relationship between heart rate and blood pressure, as well as cardiorespiratory coupling, play a critical role in maintaining blood pressure and organ perfusion during conditions of blood loss. Traditional vital signs such as blood pressure, breathing rate, and oxygen saturation are poor markers of blood loss, making it difficult for medics to assess the severity of central hypovolemia. Monitoring hemorrhage is further complicated by the fact that some patients have a low tolerance to hemorrhage and would reach the point of cardiovascular collapse in less time than high tolerant individuals. Therefore, this study aimed to investigate the potential of the physiological interaction between heart rate and blood pressure, and cardiorespiratory coupling to track the progression of simulated hemorrhage, as well as distinguish individuals with low tolerance (LT) from the ones with high tolerance (HT) to hypovolemia. Nineteen subjects (age: 28 ± 6 years; height: 170 ± 7 cm; weight: 68 ± 10 kg) underwent a progressive lower body negative pressure (LBNP) protocol in which the participant was supine inside the chamber for 12 min (baseline) before 12 min of chamber decompression at -20, -30, -40, -50 and -60 mmHg followed by a 12 min recovery period. Twelve subjects reached presyncope before or during -60 mmHg LBNP stage and were considered low tolerant (LT, 12 participants), while the ones who completed -60 mmHg were considered high tolerant (HT, 7 participants). Continuous blood pressure (BP), respiration (RSP), and electrocardiogram (ECG) signals were acquired simultaneously during baseline and each LBNP stage. RR interval was calculated using ECG, while systolic blood pressure (SBP), and pulse pressure were derived from BP waveform. Wavelet transform coherence and convergent cross-mapping techniques were employed to study the physiological interdependence and the causal relationship between heart rate, blood pressure, and respiration. The interaction between blood pressure and heart rate in terms of gain, active gain, and fraction time active(SBP↔RR,PP↔RR)to maintain homeostasis was higher in the LT group during baseline, and LBNP simulated mild, moderate, and severe hemorrhage. The significant time of interaction between SBP and RSP, and the causal effect of blood pressure on respiration were higher in the HT group during baseline compared to the LT group. HT participants also had a higher causal effect of respiration on blood pressure(RSP→SBP,RSP→PP)during -30 and -40 mmHg compared to LT. Moreover, the HT group displayed a higher causal drive of respiratory-related changes in heart rate(RSP→RR)and heart rate mediated changes in respirationRR→RSPduring severe simulated hemorrhage (-40 mmHg) compared to the LT group. The calculated metrics to distinguish between individual LT from HT subjects achieved a sensitivity of 58%-83%, an accuracy of 63%-84%, and an area under the ROC curve of 74%-86%, while the overlap of LT individual responses with HT was 0%-33%. These results indicate the potential of cardiorespiratory coupling, and heart rate and blood pressure interaction toward tracking the progression of hemorrhage and distinguishing individuals with low tolerance to hypovolemia from those with high tolerance. Measurements of such interactions could improve clinical outcomes for patients with low tolerance to hypovolemia and therefore reduce morbidity and mortality through early implementation of life-saving interventions.

Canadian aging and inactivity study: Spaceflight-inspired exercises during head-down tilt bedrest blunted reductions in muscle-pump but not cardiac baroreflex in older persons.

As part of the first Canadian aging and inactivity study (CAIS) we assessed the efficacy of space-based exercise countermeasures for maintenance of cardiac and muscle-pump baroreflex in older persons during bedrest. An initiative of the Canadian Space Agency, Canadian Institutes of Health Research and the Canadian Frailty Network, CAIS involved 14 days of 6-degree head-down tilt bedrest (HDBR) with (Exercise) or without (Control) combined upper and lower body strength, aerobic, and high-intensity interval training exercise countermeasures. Twenty healthy men and women aged 55 to 65, randomly divided into control and exercise groups (male control (MC, n = 5), male exercise (ME, n = 5), female control (FC, n = 6), female exercise (FE, n = 4)) (age: 58.7 ± 0.5 years, height: 1.67 ± 0.02 m, body mass: 70.2 ± 3.2 kg; mean ± SEM), completed the study. Cardiac and muscle-pump baroreflex activity were assessed with supine-to-stand tests. Wavelet transform coherence was used to characterise cardiac and muscle-pump baroreflex fraction time active (FTA) and gain values, and convergent cross-mapping was used to investigate causal directionality between blood pressure (BP) and heart rate, as well as BP and lower leg muscle electromyography (EMG). Seven of the twenty participants were unable to stand for 6 minutes after HDBR, with six of those being female. Our findings showed that 2 weeks of bedrest impaired skeletal muscle's ability to return blood to the venous circulation differently across various sexes and intervention groups. Comparing values after bed rest with before bed rest values, there was a significant increase in heart rates (∆ of +25%; +17% in MC to +33% in FC; p < 0.0001), beat-to-beat EMG decreased (∆ of -43%; -25% in ME to -58% in MC; p < 0.02), while BP change was dependent on sex and intervention groups. Unlike their male counterparts, in terms of muscle-pump baroreflex, female participants had considerably decreased FTA after HDBR (p < 0.01). All groups except female control demonstrated parallel decreases in cardiac active gain and causality, while the FC demonstrated an increase in cardiac causality despite a similar decline in cardiac active gain. Results showed that the proposed exercises may alleviate muscle-pump baroreflex declines but could not influence the cardiac baroreflex decline from 14 days of inactivity in older adults.

Numerical study of patient-specific ankle-foot orthoses for drop foot patients using shape memory alloy.

Drop foot is a nerve-muscle disorder that affects the muscles that lift the foot. The two main side effects of drop foot are slapping/kicking the foot after heel strike (foot) and dragging the foot during the swing (toe drag). Treatment methods such as ankle-foot orthoses (AFO) have some biomechanical benefits, but are not applicable to all walking conditions and cannot mitigate significant gait complications. This study introduces the design of a passive AFO system, which combines an ordinary AFO and a shape memory alloy (SMA) element. OpenSim was used to simulate patients with muscle weakness and to calculate the torque needed to imitate normal ankle joint stiffness. The calculated torque was then reproduced for different levels of muscle weakness by the superelasticity of SMAs. The study showed that the normal joint stiffness profile for each patient with a certain level of muscle weakness can be restored by designing a patient-specific orthosis.