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.

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.

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).

Significant role of the cardiopostural interaction in blood pressure regulation during standing.

Cardiovascular and postural control systems have been studied independently despite the increasing evidence showing the importance of cardiopostural interaction in blood pressure regulation. In this study, we aimed to assess the role of the cardiopostural interaction in relation to cardiac baroreflex in blood pressure regulation under orthostatic stress before and after mild exercise. Physiological variables representing cardiovascular control (heart rate and systolic blood pressure), lower limb muscle activation (electromyography), and postural sway (center of pressure derived from force and moment data during sway) were measured from 17 healthy participants (25 ± 2 yr, 9 men and 8 women) during a sit-to-stand test before and after submaximal exercise. The cardiopostural control (characterized by baroreflex-mediated muscle-pump effect in response to blood pressure changes, i.e., muscle-pump baroreflex) was assessed using wavelet transform coherence and causality analyses in relation to the baroreflex control of heart rate. Significant cardiopostural blood pressure control was evident counting for almost half of the interaction time with blood pressure changes that observed in the cardiac baroreflex (36.6-72.5% preexercise and 34.7-53.9% postexercise). Thus, cardiopostural input to blood pressure regulation should be considered when investigating orthostatic intolerance. A reduction of both cardiac and muscle-pump baroreflexes in blood pressure regulation was observed postexercise and was likely due to the absence of excessive venous pooling and a less stressed system after mild exercise. With further studies using more effective protocols evoking venous pooling and muscle-pump activity, the cardiopostural interaction could improve our understanding of the autonomic control system and ultimately lead to a more accurate diagnosis of cardiopostural dysfunctions.NEW & NOTEWORTHY We examined the interaction between cardiovascular and postural control systems during standing before and after mild exercise. Significant cardiopostural input to blood pressure regulation was shown, suggesting the importance of cardiopostural integration when investigating orthostatic hypotension. In addition, we observed a reduction of baroreflex-mediated blood pressure regulation after exercise.

Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

BACKGROUND AND PURPOSE: Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. METHODS: We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. RESULTS: Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. CONCLUSIONS: Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

Physiological interdependence of the cardiovascular and postural control systems under orthostatic stress.

The cardiovascular system has been observed to respond to changes in human posture and the environment. On the same lines, frequent fallers have been observed to suffer from cardiovascular deficits. The present article aims to demonstrate the existence of interactions between the cardiovascular and postural control systems. The behavior of the two systems under orthostatic challenge was studied through novel adaptations of signal processing techniques. To this effect, the interactions between the two systems were assessed with two metrics, coherence and phase lock value, based on the wavelet transform. Measurements from the cardiovascular system (blood pressure), lower limb muscles (surface electromyography), and postural sway (center of pressure) were acquired from young healthy adults (n = 28, men = 12, age = 20-28 yr) during quiet stance. The continuous wavelet transform was applied to decompose the representative signals on a time-scale basis in a frequency region of 0.01 to 0.1 Hz. Their linear coupling was quantified through a coherence metric, and the synchrony was characterized via the phase information. The outcomes of this study present evidence that the cardiovascular and postural control systems work together to maintain homeostasis under orthostatic challenge. The inferences open a new direction of study for effects under abnormalities and extreme environmental conditions.

Statistical validation of wavelet transform coherence method to assess the transfer of calf muscle activation to blood pressure during quiet standing.

BACKGROUND: Continuous and discrete wavelet transforms have been established as valid tools to analyze non-stationary and transient signals over Fourier domain methods. Additionally, Fourier transform based coherence methods provide aggregate results but do not provide insights into the changes in coherent behavior over time, hence limiting their utility. METHODS: Statistical validation of the wavelet transform coherence (WTC) was conducted with simulated data sets. Time frequency maps of signal coherence between calf muscle electromyography (EMG) and blood pressure (BP) were obtained by WTC to provide further insight into their interdependent time-varying behavior via the skeletal muscle pump during quiet stance. Data were collected from healthy young males (n = 5, 19-28 years) during a quiet stance on a balance platform. Waveforms for EMG and BP were acquired and processed for further analysis. RESULTS: Low values of bias and standard deviation (< 0.1) were observed and the use of both simulated and real data demonstrated that the WTC method was able to identify time points of significant coherence (> Threshold) and objectively detect existence of interdependent activity between the calf muscle EMG and blood pressure. CONCLUSIONS: The WTC method effectively identified the presence of linear coupling between the EMG and BP signals during quiet standing. Future studies with more human data are needed to establish the exact characteristics of the identified relationship.

Cerebrovascular autoregulation: lessons learned from spaceflight research.

This review summarizes our current understanding of cerebral blood flow regulation with exposure to microgravity, outlines potential mechanisms associated with post-flight orthostatic intolerance, and proposes future directions for research and linkages with cerebrovascular disorders found in the general population. It encompasses research from cellular mechanisms (e.g. hind limb suspension: tissue, animal studies) to whole body analysis with respect to understanding human responses using space analogue studies (bed rest, parabolic flight) as well as data collected before, during, and after spaceflight. Recent evidence indicates that cerebrovascular autoregulation may be impaired in some astronauts leading to increased susceptibility to syncope upon return to a gravitational environment. The proposed review not only provides insights into the mechanisms of post-flight orthostatic intolerance, but also increases our understanding of the mechanisms associated with pathophysiological conditions (e.g. unexplained syncope) with clinical applications in relation to postural hypotension or intradialytic hypotension.

Maximizing information from space data resources: a case for expanding integration across research disciplines.

Regulatory systems are affected in space by exposure to weightlessness, high-energy radiation or other spaceflight-induced changes. The impact of spaceflight occurs across multiple scales and systems. Exploring such interactions and interdependencies via an integrative approach provides new opportunities for elucidating these complex responses. This paper argues the case for increased emphasis on integration, systematically archiving, and the coordination of past, present and future space and ground-based analogue experiments. We also discuss possible mechanisms for such integration across disciplines and missions. This article then introduces several discipline-specific reviews that show how such integration can be implemented. Areas explored include: adaptation of the central nervous system to space; cerebral autoregulation and weightlessness; modelling of the cardiovascular system in space exploration; human metabolic response to spaceflight; and exercise, artificial gravity, and physiologic countermeasures for spaceflight. In summary, spaceflight physiology research needs a conceptual framework that extends problem solving beyond disciplinary barriers. Administrative commitment and a high degree of cooperation among investigators are needed to further such a process. Well-designed interdisciplinary research can expand opportunities for broad interpretation of results across multiple physiological systems, which may have applications on Earth.

Blood volume redistribution during hypovolemia.

BACKGROUND: The goal of this study was to investigate the contribution of splanchnic volume redistribution and lower limb vasoconstriction in the maintenance of blood pressure during progressive central hypovolemia induced by graded lower body negative pressure (LBNP). It was hypothesized that splanchnic blood volume loss during LBNP would buffer decreases in thoracic blood volume. METHODS: There were 15 healthy subjects (8 men, 7 women) who participated in the study. We used LBNP of -10, -20, -30, and -40 mmHg with segmental impedance analysis to determine central and splanchnic volume changes, and near infrared spectroscopy (NIRS) to assess calf venous volume changes and vasoconstrictor tone. RESULTS: In relation to baseline, LBNP to -40 mmHg resulted in a 57% increase in deoxygenated blood in the calf, indicating venous pooling in the lower limbs. These events led to a decrease in venous return and a 28% decline in cardiac output. Total upper body impedance increased by 6.6% with a 2.4% change in thoracic and a 13.1% increase in splanchnic impedance with progressive LBNP. Splanchnic blood volume contributed to more than 50% of the volume redistribution to the thoracic compartment during hypovolemia. Both men and women increased their heart rate, but only men vasoconstricted (4.4%) with increasing LBNP. The net result of these events was the maintenance of mean arterial blood pressure with no presyncopal symptoms in these subjects. DISCUSSION: Our results suggest that splanchnic blood volume redistribution--rather than leg vasoconstriction--plays an important role in blood pressure regulation during central hypovolemia.

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.

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.

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.

Peripheral vascular responses of men and women to LBNP.

BACKGROUND: This study examined the hypothesis that women exhibit smaller vasoconstrictor responses in the calf during graded lower body negative pressure (LBNP). METHODS: Selective deep oxygenated hemoglobin (Hb) assessed by near-infrared spectroscopy (NIRS) was used to examine blood flow changes in the calf. Eleven men and nine women volunteers underwent graded LBNP up to -60 mm Hg. Cardiovascular responses were measured by: NIRS on the forearm and superficial and deep calf for oxygenated and deoxygenated Hb; mercury strain gauge plethysmography for calf blood pooling; electrocardiogram for heart rate; and, photoplethysmography for blood pressure, cardiac output, and total peripheral resistance. RESULTS: Cardiac output was lower and total peripheral resistance higher in women; however, both men and women had similar decreases in cardiac output and increases in total peripheral resistance with LBNP. Forearm oxygenated Hb decreased from baseline throughout LBNP, and no difference was found between men and women. Female subjects had greater rates of increased blood pooling with LBNP than their male counterparts. Men had greater selective deep calf oxygenated Hb reductions compared to women during LBNP. Moreover, when the oxygenated Hb response as a function of calf blood pooling was examined with regression analyses, men had greater slopes (-0.62 +/- 0.05) than women (-0.33 +/- 0.04). CONCLUSION: The greater slopes in oxygenated Hb at given blood pooling and at each negative pressure in male subjects led us to conclude that men had greater vasoconstrictor responses in the calf during graded LBNP.

Heart rate and daily physical activity with long-duration habitation of the International Space Station.

INTRODUCTION: We investigated the pattern of activity and heart rate (HR) during daily living on the International Space Station (ISS) compared to on Earth in 7 long-duration astronauts to test the hypotheses that the HR responses on the ISS would be similar to preflight values, although the pattern of activity would shift to a dominance of arm activity, and postflight HR would be elevated compared to preflight during similar levels of activity. METHODS: HR and ankle and wrist activity collected for 24-h periods before, during, and after spaceflight were divided into night, morning, afternoon, and evening segments. Exercise was excluded and analyzed separately. RESULTS: Consistent with the hypotheses, HR during daily activities on the ISS was unchanged compared to preflight; activity patterns shifted to predominantly arm in space. Contrary to the hypothesis, only night time HR was elevated postflight, although this was very small (+4 +/- 3 bpm compared to preflight). A trend was found for higher postflight HR in the afternoon (+10 +/- 10 bpm) while ankle activity level was not changed (99 +/- 48, 106 +/- 52 counts pre- to postflight, respectively). Astronauts engaged in aerobic exercise 4-8 times/week, 30-50 min/session, on a cycle ergometer and treadmill. Resistance exercise sessions were completed 4-6 times/week for 58 +/- 14 min/session. DISCUSSION: Astronauts on ISS maintained their HR during daily activities; on return to Earth there were only very small increases in HR, suggesting that cardiovascular fitness was maintained to meet the demands of normal daily activities.

Mechanisms Underlying Isovolumic Contraction and Ejection Peaks in Seismocardiogram Morphology.

A three-dimensional (3D) finite element electromechanical model of the heart is employed in simulations of seismocardiograms (SCGs). To simulate SCGs, a previously developed 3D model of ventricular contraction is extended by adding the mechanical interaction of the heart with the chest and internal organs. The proposed model reproduces the major peaks of seismocardiographic signals during the phases of the cardiac cycle. Results indicate that SCGs record the pressure of the heart acting on the ribs. In addition, the model reveals that the rotation of the rib with respect to the heart has a minor effect on seismocardiographic signal morphology during the respiratory cycle. SCGs are obtained from 24 human volunteers and their morphology is analyzed. Experimental results demonstrate that the peak of the maximum acceleration of blood in the aorta occurs at the same time as the global minimum of the SCG. It is confirmed that the first SCG peak after the electrocardiogram R-wave corresponds to aortic valve opening, as determined from the impedance cardiogram (p = 0.92). The simulation results reveal that the SCG peaks corresponding to aortic valve opening and the maximum acceleration of blood in the aorta result from ventricular contraction in the longitudinal direction of the ventricles and a decrease in the dimensions of the ventricles due to the ejection of blood, respectively.

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.