Comparison of Autonomic Control of Blood Pressure During Standing and Artificial Gravity Induced via Short-Arm Human Centrifuge

Autonomic control of blood pressure is essential toward maintenance of cerebral perfusion during standing, failure of which could lead to fainting. Long-term exposure to microgravity deteriorates autonomic control of blood pressure. Consequently, astronauts experience orthostatic intolerance on their return to gravitational environment. Ground-based studies suggest sporadic training in artificial hypergravity can mitigate spaceflight deconditioning. In this regard, short-arm human centrifuge (SAHC), capable of creating artificial hypergravity of different g-loads, provides an auspicious training tool. Here, we compare autonomic control of blood pressure during centrifugation creating 1-g and 2-g at feet with standing in natural gravity. Continuous blood pressure was acquired simultaneously from 13 healthy participants during supine baseline, standing, supine recovery, centrifugation of 1-g, and 2-g, from which heart rate (RR) and systolic blood pressure (SBP) were derived. The autonomic blood pressure regulation was assessed via spectral analysis of RR and SBP, spontaneous baroreflex sensitivity, and non-linear heart rate and blood pressure causality (RR↔SBP). While majority of these blood pressure regulatory indices were significantly different (p < 0.05) during standing and 2-g centrifugation compared to baseline, no change (p > 0.05) was observed in the same indices during 2-g centrifugation compared to standing. The findings of the study highlight the capability of artificial gravity (2-g at feet) created via SAHC toward evoking blood pressure regulatory controls analogous to standing, therefore, a potential utility toward mitigating deleterious effects of microgravity on cardiovascular performance and minimizing post-flight orthostatic intolerance in astronauts

Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance

BACKGROUND: Upon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience post-flight orthostatic intolerance was different pre-flight and/or was differentially affected by short duration (8 – 16 days) spaceflight. HRV data from ten-minute stand tests collected from the 29 astronauts 10 days pre-flight, on landing day and three days post-flight were analysed using coarse graining spectral analysis. From the total power (P(TOT)), the harmonic component was extracted and divided into high (P(HI): >0.15 Hz) and low (P(LO): = 0.15 Hz) frequency power regions. Given the distribution of autonomic nervous system activity with frequency at the sinus node, P(HI)/P(TOT )was used as an indicator of parasympathetic activity; P(LO)/P(TOT )as an indicator of sympathetic activity; and, P(LO)/P(HI )as an estimate of sympathovagal balance. RESULTS: Twenty-one astronauts were classified as finishers, and eight as non-finishers, based on their ability to remain standing for 10 minutes on landing day. Pre-flight, non-finishers had a higher supine P(HI)/P(TOT )than finishers. Supine P(HI)/P(TOT )was the same pre-flight and on landing day in the finishers; whereas, in the non-finishers it was reduced. The ratio P(LO)/P(HI )was lower in non-finishers compared to finishers and was unaffected by spaceflight. Pre-flight, both finishers and non-finishers had similar supine values of P(LO)/P(TOT), which increased from supine to stand. Following spaceflight, only the finishers had an increase in P(LO)/P(TOT )from supine to stand. CONCLUSIONS: Both finishers and non-finishers had an increase in sympathetic activity with stand on pre-flight, yet only finishers retained this response on landing day. Non-finishers also had lower sympathovagal balance and higher pre-flight supine parasympathetic activity than finishers. These results suggest pre-flight autonomic status and post-flight impairment in autonomic control of the heart may contribute to orthostatic intolerance. The mechanism by which higher pre-flight parasympathetic activity might contribute to post-flight orthostatic intolerance is not understood and requires further investigation

Orthostatic intolerance in older persons: etiology and countermeasures

Orthostatic challenge produced by upright posture may lead to syncope if the cardiovascular system is unable to maintain adequate brain perfusion. This review outlines orthostatic intolerance related to the aging process, long-term bedrest immobilization, drugs, and disease. Aging-associated illness or injury due to falls often leads to hospitalization. Given that older patients spend up to 83% of hospital admission lying in bed, immobilization - and its consequences such as physiological deconditioning, functional decline, and orthostatic intolerance - represents a central challenge in the care of the vulnerable older population. This review examines current scientific knowledge regarding orthostatic intolerance and how it comes about, thereby contributing to understanding of (patho-) physiological concepts of cardiovascular (in-) stability in ambulatory and bedrest confined senior citizens as well as in individuals with disease conditions (e.g. orthostatic intolerance in patients with diabetes mellitus, multiple sclerosis, Parkinson’s, spinal cord injury, SCI) or those on multiple medications (polypharmacy). Understanding these aspects, along with cardio- postural interactions, is particularly important as blood pressure destabilization leading to orthostatic intolerance affects 3-4% of the general population, and in 4 out of 10 cases the exact cause remains elusive. Reviewed also are countermeasures to orthostatic intolerance such as exercise, water drinking, mental arithmetic, cognitive training and respiration training in SCI patients. In addition, timing of countermeasure application is also discussed. We speculate that optimally applied countermeasures such as mental challenge maintain sympathetic activity, and improves venous return, stroke volume, and consequently, blood pressure during upright standing. Finally, this paper emphasizes the importance of an active life style in old age and why early re- mobilization following immobilization or bedrest is crucial in fall prevention in older persons

Evaluating the Efficacy of an Active Compression Brace on Orthostatic Cardiovascular Responses

Orthostatic intolerance, one of the principle causes of syncope, can occur secondary to concomitant venous pooling and enhanced capillary filtration. We aimed to evaluate a prototype portable calf active compression brace (ACB) designed to improve orthostatic haemodynamic control. Fourteen healthy volunteers participated in a randomized, placebo controlled, cross-over, double-blind study. Testing consisted of head-upright tilting and walking on a treadmill conducted on two consecutive days with a pair of ACBs wrapped around both calves. The ACB was actuated on one test day, but not on the other (placebo). Wearability, comfort, and ambulatory use of the ACB were assessed using questionnaires. The average calf pressure exerted by the ACB was 46.3±2.2 mmHg and the actuation pressure was 20.7±1.7 mmHg. When considering the differences between ACB actuation and placebo during tilt after supine rest there were trends for a larger stroke volume (+5.20±2.34%, p = 0.05) and lower heart rate (-5.12±2.41%, p = 0.06) with ACB actuation, with no effect on systolic arterial pressure (+4.86±3.41%, p = 0.18). The decrease in stroke volume after ten minutes of tilting was positively correlated with the height:calf circumference (r = 0.464; p = 0.029; n = 22; both conditions combined). The increase in heart rate after ten minutes of tilting was negatively correlated with the height:calf circumference (r = -0.485; p = 0.022; n = 22; both conditions combined) and was positively correlated with the average calf circumference (r = 0.539; p = 0.009; n = 22; both conditions combined). Participants reported good ACB wearability and comfort during ambulatory use. These data verify that the ACB increased stroke volume during tilting in healthy controls. Active calf compression garments may be a viable option for the management of orthostatic intolerance

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 \u3c 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

Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR SBP and RR MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR SBP and RR MAP) showed a significantly (p \u3c 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP RR and MAP RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR SBP (p = 0.76), RR MAP (p = 0.60), and SBP RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression

Effects of Individualized Centrifugation Training on Orthostatic Tolerance in Men and Women

Aims Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known. Methods We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure (90 minutes) in supine position [protocol 1, artificial gravity exposure], or 2) lay supine on the centrifuge for 90 minutes in supine position without AG exposure [protocol 2, control]. The AG training protocol was individualized, by first determining each subject’s maximum tolerable G load, and then exposing them to 45 minutes of ramp training at sub-presyncopal levels. Results Both sexes had improved OTL (14 minutes vs 11 minutes, p < 0.0019) following AG exposure. When cardiovascular (CV) variables at presyncope in the control test were compared with the CV variables at the same tilt-test time (isotime) during post-centrifuge, higher blood pressure, stroke volume and cardiac output and similar heart rates and peripheral resistance were found post-centrifuge. Conclusions These data suggest a better-maintained central circulating blood volume post-centrifugation across gender and provide an integrated insight into mechanisms of blood pressure regulation and the possible implementation of in-flight AG countermeasure profiles during spaceflights

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

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

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 cardio-postural interaction in blood pressure regulation. In this study, we aimed to assess the role of cardio-postural 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 years; 8 females) during a sit-to stand test before and after sub-maximal exercise. The cardio-postural 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 cardio-postural 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% pre-exercise and 34.7-53.9% post-exercise). Thus, cardio-postural 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 post-exercise 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 cardio-postural interaction could improve our understanding of the autonomic control system and ultimately lead to a more accurate diagnosis of cardio-postural dysfunctions