AN IN SILICO-IN VIVO FRAMEWORK FOR THE ACUTE OCULAR AND CARDIOVASCULAR RESPONSE TO 6° HEAD-DOWN TILT

Ensuring the healthiness of astronauts undergoing long-term missions in space is of primary importance for the aerospace community. Spaceflight associated neuro-ocular syndrome (SANS) has been widely acknowledged to cause severe ocular disorders in astronauts returning from long permanence in weightlessness [1]. In this context, head-down tilt (HDT) has gained large popularity to resemble the cardiovascular response to microgravity, as well as to study SANS [2]. We propose a novel multiscale numerical framework to simulate the acute response to 6° HDBR – with in vivo validation – to help shed light on SANS onset

Short-Term Cardiovascular Response to Short-Radius Centrifugation With and Without Ergometer Exercise

Artificial gravity (AG) has often been proposed as an integrated multi-system countermeasure to physiological deconditioning associated with extended exposure to reduced gravity levels, particularly if combined with exercise. Twelve subjects underwent short-radius centrifugation along with bicycle ergometry to quantify the short-term cardiovascular response to AG and exercise across three AG levels (0 G or no rotation, 1 G, and 1.4 G; referenced to the subject’s feet and measured in the centripetal direction) and three exercise intensities (25, 50, and 100 W). Continuous cardiovascular measurements were collected during the centrifugation sessions using a non-invasive monitoring system. The cardiovascular responses were more prominent at higher levels of AG and exercise intensity. In particular, cardiac output, stroke volume, pulse pressure, and heart rate significantly increased with both AG level (in most of exercise group combinations, showing averaged increments across exercise conditions of 1.4 L/min/g, 7.6 mL/g, 5.22 mmHg/g, and 2.0 bpm/g, respectively), and workload intensity (averaged increments across AG conditions of 0.09 L/min/W, 0.17 mL/W, 0.22 mmHg/W, and 0.74 bpm/W respectively). These results suggest that the addition of AG to exercise can provide a greater cardiovascular benefit than exercise alone. Hierarchical regression models were fitted to the experimental data to determine dose-response curves of all cardiovascular variables as a function of AG-level and exercise intensity during short-radius centrifugation. These results can inform future studies, decisions, and trade-offs toward potential implementation of AG as a space countermeasure

Virtual Reality "exergames": A promising countermeasure to improve motivation and restorative effects during long duration spaceflight missions

Long duration spaceflight missions will require novel exercise systems to protect astronaut crew from the detrimental effects of microgravity exposure. The SPRINT protocol is a novel and promising exercise prescription that combines aerobic and resistive training using a flywheel device, and it was successfully employed in a 70-day bed-rest study as well as onboard the International Space Station. Our team created a VR simulation to further augment the SPRINT protocol when using a flywheel ergometer training device (the Multi-Mode Exercise Device or M-MED). The simulation aspired to maximal realism in a virtual river setting while providing real-time biometric feedback on heart rate performance to subjects. In this pilot study, five healthy, male, physically-active subjects aged 35 +/- 9.0 years old underwent 2 weeks of SPRINT protocol, either with or without the VR simulation. After a 1-month washout period, subjects returned for a subsequent 2 weeks in the opposite VR condition. We measured physiological and cognitive variables of stress, performance, and well-being. While physiological effects did not suggest much difference with the VR condition over 2 weeks, metrics of motivation, affect, and mood restoration showed detectable differences, or trended toward more positive outcomes than exercise without VR. These results provide evidence that a well-designed VR "exergaming" simulation with biometric feedback could be a beneficial addition to exercise prescriptions, especially if users are exposed to isolation and confinement.This project was funded through an internal seed grant mechanism by the College of Engineering and the Human Clinical Research Facility at Texas A&M University, College Station, TX, United States

The impact of the COVID-19 lockdown on human psychology and physical activity; a space analogue research perspective

Introduction Astronauts will encounter isolated, confined and extreme (ICE) conditions during future missions, and will have to be able to adapt. Until recently, however, few places on Earth could serve as acceptable space analogues (i.e., submarine and polar regions). The coronavirus disease-2019 (COVID-19)-related lockdowns around the globe provided a good opportunity to obtain more comprehensive datasets on the impact of prolonged isolation on human functioning in a very large sample. Methods Seven hundred forty-eight individuals (Belgium 442, Spain 183, Germany 50, Italy 50, US 23; Mean age +/- SD: 41 +/- 14 years, with an age range of 18-83 years; 66% women) filled out an online survey assessing the impact of the COVID-lockdown on psychological, exercise and general health variables a first time near the beginning of the initial lockdown (hereafter 'T1'; 24 +/- 13 days after the start of the first lockdown; i.e., 3 weeks after the start of the first lockdown) and a second time a couple of weeks thereafter (hereafter 'T2'; 17 +/- 5 days after the first online survey; i.e., 6 weeks after the start of the first lockdown). Results From T1 to T2 an improvement of subjective sleep quality was observed (P = 0.003), that was related to an increase in subjective sleep efficiency and a decrease in sleep latency and disturbance (P <= 0.013). Weekly sitting time decreased, and the weekly amount of moderate and vigorous physical activity increased from T1 to T2 (P <= 0.049). No differences from T1 to T2 were observed in terms of mood, loneliness and state anxiety. A lower amount of sitting time was significantly correlated with improved subjective sleep quality (r = 0.096, P = 0.035) and with an increased amount of moderate (r = -0.126, P = 0.005) and vigorous (r = -0.110, P = 0.015) physical activity. Conclusion Compared to 3 weeks into the first COVID-imposed lockdown, 6-weeks after the start of the first COVID-imposed lockdown, physical activity and subjective sleep scores were positively impacted. The present, large sample size study further confirms exercise as a worthwhile countermeasure to psycho-physiological deconditioning during confinement

Human Perception of Whole-Body Roll Tilt Orientation in a Hypo-Gravity Analog: Underestimation and Adaptation

Overestimation of roll tilt in hypergravity (&ldquo;G-excess&rdquo; illusion) has been demonstrated, but corresponding sustained hypogravic conditions are impossible to create in ground laboratories. In this article we describe the first systematic experimental evidence that in a hypogravity analog, humans underestimate roll tilt. We studied perception of self-roll tilt in nine subjects, who were supine while spun on a centrifuge to create a hypogravity analog. By varying the centrifuge rotation rate, we modulated the centripetal acceleration (GC) at the subject&rsquo;s head location (0.5 or 1 GC) along the body axis. We measured orientation perception using a subjective visual vertical task in which subjects aligned an illuminated bar with their perceived centripetal acceleration direction during tilts (&plusmn;11.5&ndash;28.5&deg;). As hypothesized, based on the reduced utricular otolith shearing, subjects initially underestimated roll tilts in the 0.5 GC condition compared with the 1 GC condition (mean perceptual gain change = &minus;0.27, P = 0.01). When visual feedback was given after each trial in 0.5 GC, subjects&rsquo; perceptual gain increased in approximately exponential fashion over time (time constant = 16 tilts or 13 min), and after 45 min, the perceptual gain was not significantly different from the 1 GC baseline (mean gain difference between 1 GC initial and 0.5 GC final = 0.16, P = 0.3). Thus humans modified their interpretation of sensory cues to more correctly report orientation during this hypogravity analog. Quantifying the acute orientation perceptual learning in such an altered gravity environment may have implications for human space exploration on the moon or Mars. NEW &amp; NOTEWORTHY Humans systematically overestimate roll tilt in hypergravity. However, human perception of orientation in hypogravity has not been quantified across a range of tilt angles. Using a centrifuge to create a hypogravity centripetal acceleration environment, we found initial underestimation of roll tilt. Providing static visual feedback, perceptual learning reduced underestimation during the hypogravity analog. These altered gravity orientation perceptual errors and adaptation may have implications for astronauts.</p

Exercise under artificial gravity - experimental and computational approaches

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Aeronautics and Astronautics, 2015.Cataloged from PDF version of thesis.Includes bibliographical references (pages 185-191).Humans experience strong physiological deconditioning during space missions, primarily due to the weightlessness conditions. Some of these adverse consequences include bone loss, muscle atrophy, sensory-motor deconditioning, and cardiovascular adaptation, which may lead to orthostatic intolerance when astronauts are back on Earth. In order to mitigate the negative effects of weightlessness, several countermeasures are currently in place, particularly very intensive exercise protocols. However, despite these countermeasures, astronaut physiological deconditioning persists, highlighting the need for new approaches to maintain the astronauts' physiological state within acceptable limits. Artificial gravity has long been suggested as a comprehensive countermeasure that is capable of challenging all the physiological systems at the same time, therefore maintaining overall health during extended weightlessness. Ground studies have shown that intermittent artificial gravity using a short-radius centrifuge combined with ergometer exercise is effective in preventing cardiovascular and musculoskeletal deconditioning. However, these studies have been done in very different conditions, and confounding factors between the studies (including centrifuge configuration, exposure time, gravity level, gravity gradient, and use/intensity of exercise) make it very difficult to draw clear conclusions about the stimuli needed to maintain physiological conditioning in space. The first objective of this research effort is to analyze the effects of different artificial gravity levels and ergometer exercise workload on musculoskeletal and cardiovascular functions, motion sickness and comfort. Human experiments are conducted using a new configuration of the MIT Compact Radius Centrifuge, which has been constrained to a radius of 1.4 meters, the upper radial limit to fit within an ISS module without extensive structural alterations. The second objective is to develop a computational model of the cardiovascular system to gain a better understanding of the effects of exercise under a high gravity gradient on the cardiovascular system. The gravity gradient generated when using a short-radius centrifuge has not previously been investigated in detail. The model is validated with the experimental measurements from the MIT CRC. Then, the model is used to explore the cardiovascular responses to new centrifuge configurations and from 0g adapted subjects.by Ana Diaz Artiles.Ph. D

Computational model of cardiovascular response to centrifugation and lower body cycling exercise

Short-radius centrifugation combined with exercise has been suggested as a potential countermeasure against spaceflight deconditioning. Both the long-term and acute physiological responses to such a combination are incompletely understood. We developed and validated a computational model to study the acute cardiovascular response to centrifugation combined with lower body ergometer exercise. The model consisted of 21 compartments, including the upper body, renal, splanchnic, and leg circulation, as well as a four-chamber heart and pulmonary circulation. It also included the effects of gravity gradient and ergometer exercise. Centrifugation and exercise profiles were simulated and compared with experimental data gathered on 12 subjects exposed to a range of gravitational levels (1 and 1.4G measured at the feet) and workload intensities (25–100 W). The model was capable of reproducing cardiovascular changes (within ± 1 SD from the group-averaged behavior) due to both centrifugation and exercise, including dynamic responses during transitions between the different phases of the protocol. The model was then used to simulate the hemodynamic response of hypovolemic subjects (blood volume reduced by 5–15%) subjected to similar gravitational stress and exercise profiles, providing insights into the physiological responses of experimental conditions not tested before. Hypovolemic results are in agreement with the limited available data and the expected responses based on physiological principles, although additional experimental data are warranted to further validate our predictions, especially during the exercise phases. The model captures the cardiovascular response for a range of centrifugation and exercise profiles, and it shows promise in simulating additional conditions where data collection is difficult, expensive, or infeasible.NASA (Grant NCC 9-58

The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses. Keywords: promethazine, motion sickness, human experiments, vestibular perception, anti-motion sickness drug, medicationNational Space Biomedical Research Institute (NASA NCC 9-58

Gravitational Dose‐Response Curves for Acute Cardiovascular Hemodynamics and Autonomic Responses in a Tilt Paradigm

Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose‐response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head‐up tilt to 45° head‐down tilt in 15° increments, in both supine and prone postures. We measured the steady‐state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose‐response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head‐down tilt positions