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.

Exaggerated postural sway improves orthostatic cardiovascular and cerebrovascular control.

Introduction: Healthy individuals with poor cardiovascular control, but who do not experience syncope (fainting), adopt an innate strategy of increased leg movement in the form of postural sway that is thought to counter orthostatic (gravitational) stress on the cardiovascular system. However, the direct effect of sway on cardiovascular hemodynamics and cerebral perfusion is unknown. If sway produces meaningful cardiovascular responses, it could be exploited clinically to prevent an imminent faint. Methods: Twenty healthy adults were instrumented with cardiovascular (finger plethysmography, echocardiography, electrocardiogram) and cerebrovascular (transcranial Doppler) monitoring. Following supine rest, participants performed a baseline stand (BL) on a force platform, followed by three trials of exaggerated sway (anterior-posterior, AP; mediolateral, ML; square, SQ) in a randomized order. Results: All exaggerated postural sway conditions improved systolic arterial pressure (SAP, p = 0.001) responses, while blunting orthostatic reductions in stroke volume (SV, p < 0.01) and cerebral blood flow (CBFv, p < 0.05) compared to BL. Markers of sympathetic activation (power of low-frequency oscillations in SAP, p < 0.001) and maximum transvalvular flow velocity (p < 0.001) were reduced during exaggerated sway conditions. Responses were dose-dependent, with improvements in SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.009) all positively correlated with total sway path length. Coherence between postural movements and SAP (p < 0.001), SV (p < 0.001) and CBFv (p = 0.003) also improved during exaggerated sway. Discussion: Exaggerated sway improves cardiovascular and cerebrovascular control and may supplement cardiovascular reflex responses to orthostatic stress. This movement provides a simple means to boost orthostatic cardiovascular control for individuals with syncope, or those with occupations that require prolonged motionless standing.

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

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.

Mechanical deconditioning of the heart due to long-term bed rest as observed on seismocardiogram morphology.

During head-down tilt bed rest (HDT) the cardiovascular system is subject to headward fluid shifts. The fluid shift phenomenon is analogous to weightlessness experienced during spaceflight microgravity. The purpose of this study was to investigate the effect of prolonged 60-day bed rest on the mechanical performance of the heart using the morphology of seismocardiography (SCG). Three-lead electrocardiogram (ECG), SCG and blood pressure recordings were collected simultaneously from 20 males in a 60-day HDT study (MEDES, Toulouse, France). The study was divided into two campaigns of ten participants. The first commenced in January, and the second in September. Signals were recorded in the supine position during the baseline data collection (BDC) before bed rest, during 6° HDT bed rest and during recovery (R), post-bed rest. Using SCG and blood pressure at the finger, the following were determined: Pulse Transit Time (PTT); and left-ventricular ejection time (LVET). SCG morphology was analyzed using functional data analysis (FDA). The coefficients of the model were estimated over 20 cycles of SCG recordings of BDC12 and HDT52. SCG fiducial morphology AO (aortic valve opening) and AC (aortic valve closing) amplitudes showed significant decrease between BDC12 and HDT52 (p < 0.03). PTT and LVET were also found to decrease through HDT bed rest (p < 0.01). Furthermore, PTT and LVET magnitude of response to bed rest was found to be different between campaigns (p < 0.001) possibly due to seasonal effects on of the cardiovascular system. Correlations between FDA and cardiac timing intervals PTT and LVET using SCG suggests decreases in mechanical strength of the heart and increased arterial stiffness due to fluid shifts associated with the prolonged bed rest.

Effect of Parkinson's Disease on Cardio-postural Coupling During Orthostatic Challenge.

Cardiac baroreflex and leg muscles activation are two important mechanisms for blood pressure regulation, failure of which could result in syncope and falls. Parkinson's disease is known to be associated with cardiac baroreflex impairment and skeletal muscle dysfunction contributing to falls. However, the mechanical effect of leg muscles contractions on blood pressure (muscle-pump) and the baroreflex-like responses of leg muscles to blood pressure changes is yet to be comprehensively investigated. In this study, we examined the involvement of the cardiac baroreflex and this hypothesized reflex muscle-pump function (cardio-postural coupling) to maintain blood pressure in Parkinson's patients and healthy controls during an orthostatic challenge induced via a head-up tilt test. We also studied the mechanical effect of the heart and leg muscles contractions on blood pressure. We recorded electrocardiogram, blood pressure and electromyogram from 21 patients with Parkinson's disease and 18 age-matched healthy controls during supine, head-up tilt at 70°, and standing positions with eyes open. The interaction and bidirectional causalities between the cardiovascular and musculoskeletal signals were studied using wavelet transform coherence and convergent cross mapping techniques, respectively. Parkinson's patients displayed an impaired cardiac baroreflex and a reduced mechanical effect of the heart on blood pressure during supine, tilt and standing positions. However, the effectiveness of the cardiac baroreflex decreased in both Parkinson's patients and healthy controls during standing as compared to supine. In addition, Parkinson's patients demonstrated cardio-postural coupling impairment along with a mechanical muscle pump dysfunction which both could lead to dizziness and falls. Moreover, the cardiac baroreflex had a limited effect on blood pressure during standing while lower limb muscles continued to contract and maintain blood pressure via the muscle-pump mechanism. The study findings highlighted altered bidirectional coupling between heart rate and blood pressure, as well as between muscle activity and blood pressure in Parkinson's disease. The outcomes of this study could assist in the development of appropriate physical exercise programs to reduce falls in Parkinson's disease by monitoring the cardiac baroreflex and cardio-postural coupling effect on maintaining blood pressure.

Detecting Coronary Artery Disease Using Rest Seismocardiography and Gyrocardiography.

In this study, we present a non-invasive solution to identify patients with coronary artery disease (CAD) defined as ⩾50% stenosis in at least one coronary artery. The solution is based on the analysis of linear acceleration (seismocardiogram, SCG) and angular velocity (gyrocardiogram, GCG) of the heart recorded in the x, y, and z directional axes from an accelerometer/gyroscope sensor mounted on the sternum. The database was collected from 310 individuals through a multicenter study. The time-frequency features extracted from each SCG and GCG data channel were fed to a one-dimensional Convolutional Neural Network (1D CNN) to train six separate classifiers. The results from different classifiers were later fused to estimate the CAD risk for each participant. The predicted CAD risk was validated against related results from angiography. The SCG z and SCG y classifiers showed better performance relative to the other models (p < 0.05) with the area under the curve (AUC) of 91%. The sensitivity range for CAD detection was 92-94% for the SCG models and 73-87% for the GCG models. Based on our findings, the SCG models achieved better performance in predicting the CAD risk compared to the GCG models; the model based on the combination of all SCG and GCG classifiers did not achieve higher performance relative to the other models. Moreover, these findings showed that the performance of the proposed 3-axial SCG/GCG solution based on recordings obtained during rest was comparable, or better than stress ECG. These data may indicate that 3-axial SCG/GCG could be used as a portable at-home CAD screening tool.

Early Detection of Parkinson's Disease Using Center of Pressure Data and Machine Learning.

Parkinson's disease (PD) is a progressive neurodegenerative disorder resulting in abnormal body movements. Postural instability is one of the primary motor symptoms of PD and contributes to falls. Measurement of postural sway through center of pressure (COP) data might be an objective indicator of Parkinson's disease. The goal of this work is to use machine learning to evaluate if different features of postural sway can differentiate PD patients from healthy controls. Time domain, frequency domain, time-frequency, and structural features were extracted from COP data collected from 19 PD patients and 13 healthy controls (HC). The calculated parameters were input to various machine-learning models to classify PD and HC. Random Forest outperformed the rest of the classifiers in terms of accuracy, false negative rate, F1-score, and precision. Time domain features had the best performance in differentiating PD from HC compared to other feature groups.

Effect of Blood Volume Shift Simulated via Head-up Tilt on Photoplethysmography Morphology.

PPG can provide information on cardiovascular responses to fluid shifts from upper to lower part of body under the condition of orthostatic stress. The current study investigated ability of PPG derived LVET and other PPG derived features to identify progressive central hypovolemia induced by head up tilt (HUT) and evaluated potential use of LVET as early noninvasive indicator of blood loss. Continuous finger PPG, blood pressure, and electrocardiography were recorded simultaneously during 5-minutes of baseline and HUT of 20°, 40°, and 60° from 15 participants (age: 26.5 ± 3 years; height: 177 ± 8 cm; weight: 72 ± 10 kg, mean ± SD). Beat-by-beat pulse rate (PR), systolic amplitude (SA), systolic time (ST), diastolic time (DT), and PP Interval (PPI) and Ratio of pulse rate over systolic amplitude (PR/SA) were derived for each stage. LVET was derived from each stage. Friedman test followed by post-hoc analysis using Tukey-HSD was conducted to highlight the significance of changes induced by HUT. Application of 60° HUT (i.e. moderate category simulated hypovolemia) resulted in a significant change in PR (80±3 bpm vs 68±3 bpm, p=0.0008), DT (264±7 ms vs 303±4 ms, p=0.0008), ST (110±6 ms vs 117±7 ms, p=0.02), PP interval (764±39 ms vs 869±25 ms, p=0.0045), PR/SA (112±16 vs 82±21, p=0.012) , SA (0.875± 0.2 vs 1.69±0.6, p=0.012) and LVET(292 vs 351ms,p=0.0008) compared to baseline. LVET has a strong association with the change in central blood volume and may be used as a sensitive early marker of progressive hypovolemia. The findings of the study support the hypothesis of differentiating simulated hypovolemia based on PPG alone. Keywords: Hypovolemia, HUT, LVET.

Effect of novel short-arm human centrifugation-induced gravitational gradients upon cardiovascular responses, cerebral perfusion and g-tolerance.

KEY POINTS: The aim of this study was to determine the effect of rotational axis position (RAP and thus g-gradient) during short-arm human centrifugation (SAHC) upon cardiovascular responses, cerebral perfusion and g-tolerance. In 10 male and 10 female participants, 10 min passive SAHC runs were performed with the RAP above the head (P1), at the apex of the head (P2), or at heart level (P3), with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. We hypothesized that movement of the RAP from above the head (the conventional position) towards the heart might reduce central hypovolaemia, limit cardiovascular responses, aid cerebral perfusion, and thus promote g-tolerance. Moving the RAP footward towards the heart decreased the cerebral tissue saturation index, calf circumference and heart rate responses to SAHC, thereby promoting g-tolerance. Our results also suggest that RAP, and thus g-gradient, warrants further investigation as it may support use as a holistic spaceflight countermeasure. ABSTRACT: Artificial gravity (AG) through short-arm human centrifugation (SAHC) has been proposed as a holistic spaceflight countermeasure. Movement of the rotational axis position (RAP) from above the head towards the heart may reduce central hypovolaemia, aid cerebral perfusion, and thus promote g-tolerance. This study determined the effect of RAP upon cardiovascular responses, peripheral blood displacement (i.e. central hypovolaemia), cerebral perfusion and g-tolerance, and their inter-relationships. Twenty (10 male) healthy participants (26.2 ± 4.0 years) underwent nine (following a familiarization run) randomized 10 min passive SAHC runs with RAP set above the head (P1), at the apex of the head (P2), or at heart level (P3) with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. Cerebral tissue saturation index (cTSI, cerebral perfusion surrogate), calf circumference (CC, central hypovolaemia), heart rate (HR) and digital heart-level mean arterial blood pressure (MAP) were continuously recorded, in addition to incidence of pre-syncopal symptoms (PSS). ΔCC and ΔHR increases were attenuated from P1 to P3 (ΔCC: 5.46 ± 0.54 mm to 2.23 ± 0.42 mm; ΔHR: 50 ± 4 bpm to 8 ± 2 bpm, P < 0.05). In addition, ΔcTSI decrements were also attenuated (ΔcTSI: -2.85 ± 0.48% to -0.95 ± 0.34%, P < 0.05) and PSS incidence lower in P3 than P1 (P < 0.05). A positive linear relationship was observed between ΔCC and ΔHR with increasing +Gz, and a negative relationship between ΔCC and ΔcTSI, both independent of RAP. Our data suggest that movement of RAP towards the heart (reduced g-gradient), independent of foot-level Gz, leads to improved g-tolerance. Further investigations are required to assess the effect of differential baroreceptor feedback (i.e. aortic-carotid g-gradient).

Cardio-postural interactions and muscle-pump baroreflex are severely impacted by 60-day bedrest immobilization.

To understand fundamental mechanisms associated with post-flight orthostatic intolerance we investigated the interaction between the cardiovascular and postural functions before and after 60 days of head down bedrest (HDBR). Twenty healthy young males (35.0 ± 1.7 years) were subjected to 60-day HDBR at 6˚ to simulate spaceflight-induced fluid shifts. A supine-to-stand (STS) test was conducted to evaluate cardio-postural control before and after (R) HDBR while an assessment of cardiovascular function was performed during HDBR. Beat-to-beat heart period, systolic blood pressure, and electromyography impulses were derived for wavelet transform coherence and causality analyses of the cardio-postural control and used to assess changes in the muscle-pump baroreflex. During quiet stand of the STS test, compared to baseline, heart rate was 50% higher on the day of exit from bedrest (R0) and 20% higher eight days later (R8). There was a 50% increase in deoxygenated hemoglobin on R0 and R8. Leg muscle activity reduced, and postural sway increased after HDBR. Causality of the muscle-pump baroreflex was reduced on R0 (0.73 ± 0.2) compared to baseline (0.87 ± 0.2) with complete recovery by R8. The muscle-pump baroreflex also had decreased gain and fraction time active following HDBR. Overall, our data show a significantly impaired muscle-pump baroreflex following bedrest.

The repeatability of estimated systolic time intervals in healthy subjects using seismocardiogram and electrocardiogram.

OBJECTIVE: We investigated the repeatability of systolic time intervals (STIs) in healthy subjects using a combination of seismocardiogram (SCG) and electrocardiogram (ECG). STIs have been extensively used in the past to quantify heart performance, particularly the left ventricle. In this study, STIs included pre-ejection period (PEP), left ventricular ejection time (LVET), and their ratio. APPROACH: We conducted the repeatability test of STI estimation through two experiments. The first involved three consecutive one-minute recordings separated by one-minute intervals, and the second involved two one-minute recordings separated by 24 h. Twenty healthy subjects participated in our study. We considered the coefficient of variation (CV) to quantify the repeatability. As there was no agreed upon values for optimal CV values, we compared our results with an alternative method using a combination of impedance cardiography (ICG) and ECG. Similar to our method, the alternative method was noninvasive and could be employed for personal heart monitoring. We also studied the repeatability after STIs were corrected for heart rate using two approaches. The first approach used a multiplicative factor per subject based on the heart rates in each recordings of that subject. The second approach employed sex-specific regression models for all subjects (Weissler's equations). MAIN RESULTS: We found that the repeatability of our method (SCG and ECG) was in agreement with the alternative method (ICG and ECG) in both experiments. Moreover, the Weissler's equations approach for heart rate increased the repeatability. SIGNIFICANCE: It can be concluded that estimation of PEP, LVET and their ratio through SCG and ECG signals was repeatable in healthy subjects.

Identifying Patients With Coronary Artery Disease Using Rest and Exercise Seismocardiography.

Coronary artery disease (CAD) is the most common cause of death globally. Patients with suspected CAD are usually assessed by exercise electrocardiography (ECG). Subsequent tests, such as coronary angiography and coronary computed tomography angiography (CCTA) are performed to localize the stenosis and to estimate the degree of blockage. The present study describes a non-invasive methodology to identify patients with CAD based on the analysis of both rest and exercise seismocardiography (SCG). SCG is a non-invasive technology for capturing the acceleration of the chest induced by myocardial motion and vibrations. SCG signals were recorded from 185 individuals at rest and immediately after exercise. Two models were developed using the characterization of the rest and exercise SCG signals to identify individuals with CAD. The models were validated against related results from angiography. For the rest model, accuracy was 74%, and sensitivity and specificity were estimated as 75 and 72%, respectively. For the exercise model accuracy, sensitivity, and specificity were 81, 82, and 84%, respectively. The rest and exercise models presented a bootstrap-corrected area under the curve of 0.77 and 0.91, respectively. The discrimination slope was estimated 0.32 for rest model and 0.47 for the exercise model. The difference between the discrimination slopes of these two models was 0.15 (95% CI: 0.10 to 0.23, p < 0.0001). Both rest and exercise models are able to detect CAD with comparable accuracy, sensitivity, and specificity. Performance of SCG is better compared to stress-ECG and it is identical to stress-echocardiography and CCTA. SCG examination is fast, inexpensive, and may even be carried out by laypersons.

Comparison of Different Methods for Estimating Cardiac Timings: A Comprehensive Multimodal Echocardiography Investigation.

Cardiac time intervals are important hemodynamic indices and provide information about left ventricular performance. Phonocardiography (PCG), impedance cardiography (ICG), and recently, seismocardiography (SCG) have been unobtrusive methods of choice for detection of cardiac time intervals and have potentials to be integrated into wearable devices. The main purpose of this study was to investigate the accuracy and precision of beat-to-beat extraction of cardiac timings from the PCG, ICG and SCG recordings in comparison to multimodal echocardiography (Doppler, TDI, and M-mode) as the gold clinical standard. Recordings were obtained from 86 healthy adults and in total 2,120 cardiac cycles were analyzed. For estimation of the pre-ejection period (PEP), 43% of ICG annotations fell in the corresponding echocardiography ranges while this was 86% for SCG. For estimation of the total systolic time (TST), these numbers were 43, 80, and 90% for ICG, PCG, and SCG, respectively. In summary, SCG and PCG signals provided an acceptable accuracy and precision in estimating cardiac timings, as compared to ICG.

Effect of Aging on Muscle-Pump Baroreflex of Individual Leg Muscles During Standing.

Activation of leg muscles is an important component in the regulation of blood pressure during standing, failure of which could result in syncope and falls. Our previous work demonstrated baroreflex mediated activation of leg muscles (muscle-pump baroreflex) as an important factor in the regulation of blood pressure during standing; however, the effect of aging on the muscle-pump baroreflex of individual leg muscles during standing remains to be understood. Here, the interaction between systolic blood pressure (SBP) and the activation of lateral gastrocnemius (LG), medial gastrocnemius (MG), tibialis anterior (TA), and soleus (SOL) muscles during standing was quantified. Beat-to-beat heart period (RR interval), SBP, electromyography impulse (EMGimp) were derived from continuously acquired electrocardiography, finger blood pressure, and calf-electromyography, respectively. The cardiac baroreflex (SBP→RR) causality (0.88 ± 0.08 vs. 0.94 ± 0.03, p = 0.01), percent time with significant coherence (%SC: 50.95 ± 23.31 vs. 76.75 ± 16.91, p = 0.001), and gain (4.39 ± 4.38 vs. 13.05 ± 8.11, p < 0.001) was lower in older (69 ± 4 years) compared to young (26 ± 2 years) persons. Muscle-pump baroreflex (SBP→EMGimp) causality of LG (0.81 ± 0.08 vs. 0.88 ± 0.05, p = 0.01) and SOL (0.79 ± 0.11 vs. 0.88 ± 0.04, p = 0.01) muscles was lower in older compared to young persons. %SC was lower for all muscles in the older group (LG, p < 0.001; MG, p = 0.01; TA, p = 0.01; and SOL, p < 0.001) compared to young. The study outcomes highlighted impairment in muscle-pump baroreflex with age in addition to cardiac baroreflex. The findings of the study can assist in the development of an effective system for monitoring orthostatic tolerance via cardiac and muscle-pump baroreflexes to mitigate syncope and falls.