STEM Today by Abhishek Sinha

STEM TODAY February 2018, No. 29

CONTENTS Cardiovascular issues during reÂentry into Earth's atmosphere

The most profound Cardiovascular deconditioning occur during and after gravitational transitions. There is a possibility that crew will experience impaired control of the spacecraft during landing along with impaired ability to immediately egress following a landing on a planetary surface (Earth or other) after long-duration space flight.

Editorial Editor: Mr. Abhishek Kumar Sinha Editor / Technical Advisor: Mr. Martin Cabaniss

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Disclaimer ( Non-Commercial Research and Educational Use ) STEM Today is dedicated to STEM Education and Human Spaceflight. This newsletter is designed for Teachers and Students with interests in Human Spaceflight and learning about NASA’s Human Research Roadmap. The opinion expressed in this newsletter is the opinion based on fact or knowledge gathered from various research articles. The results or information included in this newsletter are from various research articles and appropriate credits are added. The citation of articles is included in Reference Section. The newsletter is not sold for a profit or included in another media or publication that is sold for a profit. Cover Page From a Million Miles Away, NASA Camera Shows Moon Crossing Face of Earth This animation still image shows the far side of the moon, illuminated by the sun, as it crosses between the DISCOVR spacecraft’s Earth Polychromatic Imaging Camera (EPIC) camera and telescope, and the Earth - one million miles away. A NASA camera aboard the Deep Space Climate Observatory (DSCOVR) satellite captured a unique view of the moon as it moved in front of the sunlit side of Earth last month. The series of test images shows the fully illuminated "dark side" of the moon that is never visible from Earth. The images were captured by NASA’s Earth Polychromatic Imaging Camera (EPIC), a four megapixel CCD camera and telescope on the DSCOVR satellite orbiting 1 million miles from Earth. From its position between the sun and Earth, DSCOVR conducts its primary mission of real-time solar wind monitoring for the National Oceanic and Atmospheric Administration (NOAA). Image Credit: NASA/NOAA

Back Cover Full Moon Full Moon. Rises at sunset, high in the sky around midnight. Visible all night. This marks the first time that accurate shadows at this level of detail are possible in such a computer simulation. The shadows are based on the global elevation map being developed from measurements by the Lunar Orbiter Laser Altimeter (LOLA) aboard the Lunar Reconnaissance Orbiter (LRO). LOLA has already taken more than 10 times as many elevation measurements as all previous missions combined. The Moon always keeps the same face to us, but not exactly the same face. Because of the tilt and shape of its orbit, we see the Moon from slightly different angles over the course of a month. Image Credit: NASA

STEM Today , February 2018

Editorial Dear Reader

STEM Today, February 2018, No.29

All young people should be prepared to think deeply and to think well so that they have the chance to become the innovators, educators, researchers, and leaders who can solve the most pressing challenges facing our world, both today and tomorrow. But, right now, not enough of our youth have access to quality STEM learning opportunities and too few students see these disciplines as springboards for their careers. According to Marillyn Hewson, "Our children - the elementary, middle and high school students of today - make up a generation that will change our universe forever. This is the generation that will walk on Mars, explore deep space and unlock mysteries that we can’t yet imagine". "They won’t get there alone. It is our job to prepare, inspire and equip them to build the future." STEM Today will inspire and educate people about Spaceflight and effects of Spaceflight on Astronauts. Editor Mr. Abhishek Kumar Sinha

Editorial Dear Reader The Science, Technology, Engineering and Math (STEM) program is designed to inspire the next generation of innovators, explorers, inventors and pioneers to pursue STEM careers. According to former President Barack Obama, " Science is more than a school subject, or the periodic table, or the properties of waves. It is an approach to the world, a critical way to understand and explore and engage with the world, and then have the capacity to change that world..." STEM Today addresses the inadequate number of teachers skilled to educate in Human Spaceflight. It will prepare , inspire and educate teachers about Spaceflight. STEM Today will focus on NASA’S Human Research Roadmap. It will research on long duration spaceflight and put together latest research in Human Spaceflight in its monthly newsletter. Editor / Technical Advisor Mr. Martin Cabaniss

STEM Today, February 2018, No.29

Human Health Countermeasures (HHC) Cardiovascular issues during re-entry into Earth's atmosphere

Spaceflight-induced cardiovascular changes during the Functional Task Test

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Microgravity exposure induces physiologic adaptations in astronauts such as sensorimotor disturbances, cardiovascular deconditioning, and loss of muscle strength and muscle mass. Natalia M. Arzeno and other authors studied the spaceflight-induced cardiovascular changes during the Functional Task Test by examining the heart rate during the functional tasks and autonomic activity, approximated by heart rate variability, during the Recovery from Fall/Stand Test and published their findings in paper " Spaceflight-induced cardiovascular changes and recovery during NASAâ&#x20AC;&#x2122;s Functional Task Test".

Seven astronauts (5 men, 2 women) taking part in 10-15-day missions participated in the Functional Task Test twice before spaceflight (30 and 60 days before launch) and four times after spaceflight (landing day and 1, 6, and 30 days after landing). The astronauts performed seven functional tests: (1) seat egress and walk, (2) recovery from fall/stand test, (3) rock translation, (4) construction activity board, (5) torque generation, (6) jump down, and (7) ladder climb. The seat egress and walk, recovery from fall/stand test, and torque generation have multiple components, each of which was analyzed separately for a total of 11 tasks (Table 1). Heart rate and R-R intervals were calculated from a 12-lead Holter monitor recording (Mortara Instrument, Mil-waukee, WI) sampled at 1 kHz. During the Recovery from Fall/Stand Test, continuous blood pressure was acquired at the finger by means of photoplethysmography using the Portapres system (Finapres Medical Systems, Netherlands) with a sampling rate of 100 Hz. The subject was instructed to not press down on the finger cuff while standing up from prone to not disturb the blood pressure signal. Results Recovery from Fall/Stand Test Mean heart rate was higher during the stand test than prone rest on all days (P < 0.001) (Fig. 1). Heart rate was higher than preflight on landing day and 1 day after landing during both the prone rest (P< 0.013) and stand test (P < 0.001). Heart rate during the stand test remained significantly higher than preflight 6 days after landing (P < 0.001). Systolic blood pressure tended to be lower during stand than prone rest (P = 0.051) while DBP was lower during the stand test than prone rest (P < 0.001). Neither mean SBP nor DBP was affected by spaceflight. As expected, the stand test was characterized by lower parasympathetic modulation (RR HF, P < 0.001), higher sympathovagal balance (RR LF/HF, P < 0.001) and higher sympathetic modulation (SBP LF, P = 0.002) than the prone rest. Spaceflight-induced alterations in autonomic activity were evident in parasympathetic modulation (RR HF), which was decreased on landing day during both the prone rest (P = 0.004) and stand test (P < 0.001), and sympathovagal balance (RR LF/HF) which was increased on landing day (P = 0.033) (Fig. 1). Parasympathetic modulation (RR HF) remained sup-

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pressed during the stand test 1 day (P = 0.002) and 6 days (P = 0.023) after landing.

Heart rate during functional tasks Landing day heart rate was higher than the preflight heart rate during all of the functional tasks (P < 0.021) (Fig. 2). Heart rate 1 day after landing remained higher than preflight during the tandem walk (P < 0.001), prone rest (P = 0.041), stand test (P < 0.001), construction activity board (P = 0.006), isometric torque (P = 0.006), isotonic torque (P = 0.006), and jump down (P < 0.001) tasks. Six days after landing, heart rate remained higher than pre-flight during the tandem walk (P < 0.001), stand test (P < 0.001), construction activity board (P < 0.001), iso-metric torque (P < 0.001), isotonic torque (P < 0.001), and jump down (P < 0.001) tasks. Heart rate 30 days after landing was not different from preflight during any of the tasks. There were two key findings in this work: (1) changes in autonomic activity historically observed in 5- to 10-min stand and tilt tests were detected during a 3-min stand test without a prior stabilization period, and (2) the post-flight increase in heart rate was observed across a variety of functional tasks. The duration of the stand test was designed to be long enough to allow for heart rate variability analyses while not being so long that a crewmember might become presyncopal, based on historical data, since that would preclude them from completing the rest of the Functional Task Test. Though shifting positions from prone to stand requires different exertion than during a traditional stand or tilt test, this aspect of the task was representative of standing up after a fall and essential to the Functional Task Test. Personnel trained in identification of presyncopal symptoms monitored every stand test to ensure the safety of the subjects. As expected, none of the crew- members became presyncopal, and authors were able to identify spaceflight-induced autonomic dysfunction during the Recovery from Fall/Stand Test. Parasympathetic modulation was diminished post-flight, as has been previously observed after Shuttle and long-duration missions. Parasympathetic modulation remained suppressed 6 days after landing during the stand test, but recovered by 30 days after landing. Most of the previous studies do not examine parasympathetic activity after landing day, yet Fritsch et al. found that the vagally mediated baroreflex was decreased post-flight and remained

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decreased 8-10 days after landing even though Eckberg found the vagally mediated baroreflex to have returned to pre-flight levels by 7-10 days after landing. The decrease in parasympathetic modulation post-flight caused a shift in sympathovagal balance on landing day. The quick recovery of sympathovagal balance despite a slower recovery of parasympathetic modulation could be due to the low subject number since RR LF/HF, authors index of sympathovagal balance, has been previously observed to be higher than pre-flight levels up to 4 days after landing.

Sympathetic activity upon landing has been reported to not be different from pre-flight values, yet most studies conclude sympathetic activity is increased by spaceflight. SBP LF, authors index of sympathetic modulation tended (day-position interaction P=0.125) to increase more with standing (prone mean ±SE, stand mean ±SE) on landing day (10 ± 3 mmHg2 , 38 ± 11 mmHg2 ) than pre-flight (7 ± 2 mmHg2 , 22 ± 8 mmHg2 ), and authors speculate that if they had more subjects, this increase on landing day would become significant. Heart rate was increased during all of the functional tasks after 10-15 days Shuttle missions, remained higher than preflight 6 days after landing during 6 of the 11 functional tasks, and was not different from pre-flight 30 days after landing during any of the tasks. Increases in heart rate and decreases in R-R interval have been historically observed immediately after spaceflight during rest or standing as well as during sleep.

Post-Spaceflight Orthostatic Hypotension occurs mostly in Women

Wendy W. Waters and other authors studied Post-Spaceflight orthostatic hypotension in men and women and published the results in paper " Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance". Post Spaceflight Orthostatic instability is a common problem in returning astronauts. In most astronauts, this is evidenced by increased heart rate responses to upright posture but not by actual hypotension. However, ∼20% of all astronauts returning from 5-16 days of spaceflight experience inadequate cardiovascular responses during orthostatic challenge severe enough to cause presyncope (lightheadedness, loss of peripheral vision, or a sudden drop in systolic blood pressure below 70 mmHg). The purpose of the study was : 1. To test the hypothesis that women are more susceptible to postspaceflight orthostatic hypotension than men. 2. Having shown that to be true, to compare and contrast supine and standing hemodynamic and neuroendocrine variables in the three classifications of astronauts: presyncopal women, presyncopal men, and nonpresyncopal men. These comparisons were made both before and after flight. 3. The relationships between plasma volume and hemodynamic responses to tilt in the three groups. 4. To test the hypothesis that the basic relationships among vascular resistance, cardiac output, and mean arterial pressure differ between presyncopal and nonpresyncopal groups. Subjects were recruited from the Astronaut Corps at Johnson Space Center (5 women, 30 men). Protocols were approved by the Johnson Space Center Institutional Review Board, and all subjects gave their written informed

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consent. Studies were conducted between 10 and 90 days before Shuttle spaceflight, on landing day (13 h after landing), and 3 days after landing. The duration of spaceflight ranged from 5 to 16 days.

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Results Incidences of presyncope No astronaut in this study became presyncopal during preflight testing. As a group, the female astronauts suffered postflight presyncope at a significantly higher rate (P= 0.001) compared with the male astronauts (Fig. 1). All five women studied (100%), but only 6 of 30 men studied (20%), were presyncopal (Fig. 1, top). Presyncopal symptoms occurred between 2 and 9 min after standing. There were no vasovagal incidents, and no subject lost consciousness.

Many astronauts, 18 of the 30 men, and 1 of the 5 women, were pilots of military high-performance jet aircraft. All other astronauts were mission specialists, mostly scientists who were not military pilots. To avoid possible differences in G tolerance due to previous experience, all pilots were removed from the data set and comparisons were repeated using only the mission specialists. Still, four times more women (100%) than men (25%) became presyncopal on landing day (Fig. 1, bottom; P= 0.02, between groups). Male and female astronauts did not differ in age (40.8 ± 1.0 vs. 41.3 ± 1.6 yr; P = 0.84), but they did differ in body surface area (1.98 ± 0.03 vs. 1.66 ± 0.05 m2 ; P < 0.001). Presyncopal and nonpresyncopal men did not differ in age (38.6 ± 1.3 vs. 41.4 ± 1.2 yr; P = 0.27) or body surface area (2.00 ± 0.06 vs. 1.98 ± 0.03 m2 ; P = 0.70). There also was no significant difference in the duration of exposure to microgravity between men and women (11.8 ± 0.5 vs. 11.1 ± 1.7 days; P = 0.58) or presyncopal and nonpresyncopal subjects (12.5 ± 1.0 vs. 11.4 ± 0.5 days; P = 0.27). Before landing, all astronauts consumed saline solution equal to 15 ml/kg body wt. After landing, presyncopal and nonpresyncopal astronauts consumed similar volumes of fluids (740.7 ± 52.7 vs. 896.6 ± 82.5 ml/ m2 ; P = 0.20). Blood volumes Table 1 depicts plasma volumes in presyncopal women, presyncopal men, and nonpresyncopal men. On landing day, all three groups had significant reductions in plasma volume from preflight, but the losses were significantly greater in the women(20%) than either group of men (7%). Three days after landing, plasma volumes were recovered. Table 2 depicts red blood cell volumes in the three groups. There were no significant differences in the spaceflight-induced losses among the groups.

Comparisons among women, presyncopal men, and nonpresyncopal men before flight Figure 2, left, shows preflight supine and standing data in the three groups. Before flight, both presyncopal groups showed a propensity toward higher cardiac output and lower vascular resistance. Women had significantly lower supine and standing mean arterial pressures and total peripheral resistances, higher supine heart

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rates, and higher supine and standing cardiac indexes than nonpresyncopal men. Women also had significantly lower supine and standing mean arterial pressures and tended to have higher heart rates and lower vascular resistances than those of the presyncopal men. Presyncopal men had significantly higher standing cardiac indexes and tended to have lower (P =0.08) standing vascular resistance than nonpresyncopal men. There were no significant intergroup differences in stroke index.

Thus, hemodynamically, presyncopal men fell between nonpresyncopal men and women in most variables. Plasma catecholamine levels are shown in Table 3 and Fig. 3. There were no preflight inter group differences in supine, standing, or standing-supine plasma epinephrine or norepinephrine.

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Comparisons between women, presyncopal men, and nonpresyncopal men on landing day Figure 2, middle, presents supine and standing data on landing day. Both women and presyncopal men had significantly lower standing mean arterial pressures than nonpresyncopal men, with presyncopal men having the lowest pressures. Women also had significantly higher standing heart rates and supine cardiac indexes than nonpresyncopal men. The three groups had virtually identical standing stroke and cardiac indexes. Women and presyncopal men both had significantly lower standing resistances than nonpresyncopal men.

On landing day, nonpresyncopal men had significantly greater standing plasma norepinephrine levels than they had preflight (Table 3). Presyncopal groups did not. In addition, they had greater standing-supine norepinephrine responses than women or presyncopal men (Fig. 3B, top). Both presyncopal groups had epinephrine release with standing that was greater than that preflight and also greater than that of the nonpresyncopal men (Table 3 and Fig. 3B, bottom). Comparisons between women, presyncopal men, and nonpresyncopal men 3 days postflight All but four subjects (1 nonpresyncopal man, 2 presyncopal men, and 1 presyncopal woman) maintained 10 min of up-right posture 3 days after landing. Mean responses of all subjects 3 days after landing are shown in Fig. 2, right. Mean arterial pressures were again significantly lower in women than men. Standing heart rates were significantly higher in presyncopal men than either women or nonpresyncopal men. Standing stroke indexes were significantly higher in women, possibly due to their high plasma volumes. Cardiac index showed similar patterns to preflight, with women and presyncopal men having higher values than the nonpresyncopal men. Total peripheral resistance also was similar to preflight, with nonpresyncopal men having the highest and women having the lowest resistances. There were no intergroup differences in supine, standing, or standingsupine plasma norepinephrine or epinephrine levels (Table 3, Fig. 3C). Hemodynamic relationships Figure 4 depicts the relationships between plasma volume and standing stroke index. Women (Fig. 4A) had a highly significant positive correlation (P < 0.001), indicating a strong dependence on plasma volume to main-

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tain standing stroke index. Presyncopal men (Fig. 4B) also had a positive correlation, although less significant (P = 0.05) than the women. The nonpresyncopal men (Fig. 4C) had no correlation between plasma volume and standing stroke index (P = 0.24).

The relationships between changes in cardiac output and changes in mean arterial pressure with upright posture on all test days are shown in Fig. 5. Preflight (Fig. 5A), all subjects compensated for falling cardiac outputs and maintained mean arterial pressures adequately. On landing day (Fig. 5B), women and presyncopal men had much greater falls in pressure than preflight, as cardiac output fell. Three days after landing (Fig. 5C), pressures were again maintained.

Figure 6 depicts the relationships between cardiac output and total peripheral resistance (supine and standing) in all subjects on all test days. Preflight (Fig. 6A), all three groups fell on the same curve; resistance

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increased exponentially as cardiac output decreased. However, women and presyncopal men operated only on the lower two-thirds of the curve. On landing day (Fig. 6B), both women and presyncopal men had standing resistance values that fell completely off the curve, indicating a loss of the normal inverse relationship between cardiac output and vascular resistance. Three days after landing (Fig. 6C), the relationships were again similar to preflight, with both presyncopal groups remaining on the lower portion of the curve. The group of astronauts most susceptible to postflight orthostatic hypotension and presyncope has at least four major defining characteristics. First, the subjects are primarily, although not exclusively, female. Second, presyncopal astronauts are characterized by low peripheral vascular resistance, both before and after flight, whether they are men or women. Third, although plasma volume loss by itself does not separate presyncopal and nonpresyncopal astronauts, compensatory adjustments to losses of plasma volume do separate them. Presyncopal astronauts are highly dependent on a normal hydration status for hemodynamic stability. The fourth finding from this study is the autonomic changes associated with spaceflight, manifested as a relative hypoadrenergic responsiveness, seem to differentially affect the subset of susceptible astronauts in a way that causes them to become presyncopal after, but not before, spaceflight.

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In this study, all five women became presyncopal on landing day (Fig. 1), and their preflight hemodynamic profile predicted their postflight susceptibility. They relied more on cardiac, rather than resistance, responses to maintain upright pressures on all occasions (Fig. 2). Several studies have reported that orthostatic hypotension is greater in women than in men. Women have greater heart rate responses than men during mental stress, standing, infusions of pressor agents, and cold pressor tests. The presyncopal women in this study experienced plasma volume losses after flight that were almost three times greater than those of the men (Table 1). In addition, they were very dependent on plasma volume to maintain standing stroke volume (Fig. 4). This put them at an extreme disadvantage. After spaceflight, the preflight female hemodynamic strategy was no longer effective in maintaining pressure. Stroke volumes and cardiac outputs fell lower than they had preflight and were not compensated for with greater increases in sympathetic response and vascular resistance (Figs. 2 and 3). These postflight conditions precipitated a collapse of pressure, and the high epinephrine release on landing day suggests a stress response was mounted as a result. On landing day, astronauts who become presyncopal do not have the ability to increase standing norepinephrine levels beyond their preflight levels, even in the presence of very low arterial pressures. Regardless of how it is reported (delta or absolute), the fact remains that presyncopal astronauts have a relative hypoadrenergic response in comparison to their nonpresyncopal counterparts.

Cerebral blood flow regulation in astronauts before and after flights

In this study Andrew P. Blaber and other authors investigated the possible importance of cerebral autoregulation on orthostatic intolerance after space flight in a sample that contained presyncopal astronauts on landing day. Authors hypothesized that autoregulation would be negatively affected by space flight in those astronauts who did not complete a 10-minute stand test (nonfinishers) when compared to those did (finishers). They have published their findings in paper "Impairment of Cerebral Blood Flow Regulation in Astronauts With Orthostatic Intolerance After Flight". This protocol was approved by the Johnson Space Center Human Research Policy and Procedures Committee. Data before and after flights were recorded from astronauts who took part in shuttle missions lasting 8 to 16 days. Data were collected 10 days before launch (baseline, before flight), on landing day (1 to 2 hours after landing), and 3 days after landing (after flight). Cerebral blood flow in the M1 segment of the middle cerebral artery (MCA) was measured using transcranial Doppler ultrasound and blood pressure via noninvasive finger photoplethysmography. The dynamic autoregulatory gain was determined using the noninvasive transfer function method. Astronauts were classified as finishers (completed the 10-minute stand test) or as nonfinishers (presyncopal during the stand test). Results Of the 27 astronauts (20 male, 7 female) who were analyzed in this study, 19 (17 male) were classified as finis-

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hers and 8 (5 female) were classified as nonfinishers. Mean arterial pressure at the level of the MCA (BPMC A ) was significantly reduced by the stand test (P < 0.001). This was combined with differences between finishers and nonfinishers (P = 0.011) and over test days (P = 0.004). On landing day, finishers had a higher BPMC A than those before flight and the nonfinishers (Figure 1). Three days after landing, the finishers had returned to preflight values whereas the nonfinishers had elevated supine BPMC A .

Mean cerebral blood flow velocity (MFV) was affected by test day (P < 0.001) and by the stand test (P < 0.01). Preflight nonfinishers had higher MFV than finishers. Compared to the preflight group, the supine MFV of the finisher group was elevated on landing day, whereas in the nonfinisher group MFV was unchanged. Un-

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like preflight MFV, on landing day both finishers and nonfinishers had a reduction in MFV with standing. Only the nonfinishers had MFV reduced lower than preflight values. Three days after landing, both supine and stand MFV were not different from preflight values for the finishers but were significantly elevated in the nonfinishers.

Cerebrovascular conductance was affected by stand (P < 0.001) and by group (P < 0.001), and it was different between finishers and nonfinishers during stand and over test days (P < 0.01). Before flight, conductance increased with the stand test; however, nonfinishers had higher conductance than finishers (Figure 1, bottom). On landing day, supine conductance was unchanged from preflight values, but the response to standing was different. On standing, conductance did not change in the finishers and decreased in the nonfinishers to a value lower than that before flight. Three days after flight, supine conductance was again higher in the nonfinishers compared to the finishers, but it did not increase on standing. There were significant gender effects with BPMC A (P = 0.035), MFV (P = 0.044), and conductance (P = 0.041), which are represented in Figure 1. Female astronauts had an increase in supine BPMC A 3 days after flight and in overall MFV 3 days after flight compared to preflight values. In general, the largest change in conductance occurred in females 3 days after flight, when cerebral conductance was greater than preflight. The effects of space flight on blood pressure at head level and cerebral blood flow velocity can be seen readily in the beat-by-beat tracing of a nonfinisher astronaut (Figure 2). Although the blood pressures in the supine and early standing conditions were similar, MFV was drastically lower. In the expanded view of presyncope, beat-by-beat differences can be seen in signals from preflight to 2 hours after landing. To further explore

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impairment of autoregulation on landing day, we plotted the average MFV against average BPMC A (Figure 3) in each of the groups. The large decline of MFV on landing day in the nonfinishers is visible, and this decrease occurred within the same blood pressure range seen before flight in both finishers and nonfinishers. A standardized autoregulation curve with arbitrary upper and lower limits was superimposed over the preflight data with the supine and standing data on the plateau of the curve (Figure 3, dashed lines). The curve was adjusted to the landing day results through a simple increase in the slope (slope, curved arrow, Figure 3) of the plateau region. The data from 3 days after flight also could be represented by a simple upward shift (plateau, vertical arrow, Figure 3) of the preflight autoregulation curve. The same pattern of increased slope of the plateau on landing day and upward shift of the curve 3 days after flight also could be observed in the group of nonfinishers but with larger changes in slope on landing day and upward shift (plateau) 3 days after flight.

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Before flight, the change in MFV as a function of BPMC A (slope of solid lines, Figure 4) was not different between males (0.16 ± 0.22 cms−1 mm Hg−1 ) and females (0.01 ± 0.51 cms−1 mm Hg−1 ; P = 0.76); however, it was greater in females on landing day (1.10 ± 0.35 cms−1 mm Hg−1 ) when compared to preflight values (P = 0.048) and compared to males on landing day (0.19 ± 0.21 cms−1 mm Hg−1 ; P = 0.06). BPMC A and Cerebrovascular Resistance Index Autospectral Data Differences in BPMC A low-frequency (LF) (0.07-0.20 Hz) power were observed between finishers and nonfinishers during the stand tests (Figure 5). On average, nonfinishers had elevated (P < 0.001) LF power (3.07 ± 0.31 mm Hg2 Hz−1 ) compared to finishers (1.49 ± 0.18 mm Hg2 Hz−1 ). There was also a significant overall difference between the finishers and nonfinishers with respect to the stand test (interaction, P < 0.001). There was a significant effect of test day on the cerebrovascular resistance index (CVRi) very-low-frequency (VLF) power between the finishers and nonfinishers (P = 0.04); the nonfinishers had significantly higher CVRi VLF power 3 days after flight (Figure 5).

BPMC A and CVRi Cross-Spectral Data Gain and Phase In the VLF region, there was a significant 3-way interaction (day, stand, presyncope; P = 0.0037). The finisher group was characterized by constant autoregulation gain in the VLF region over all test conditions (Figure 6). Preflight, the nonfinisher group had a greater supine VLF gain than did the finisher group, which decreased on standing. On landing day, the supine VLF gain of the nonfinisher group was not different from that of the finishers; however, during the stand portion the gain was greater than that of the finishers.

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Significant main effects were observed for the gain in the LF region of cerebral autoregulation. Overall, supine gain was higher than stand gain (0.043 ± 0.002 CVRu mm Hg−1 , 0.032 ± 0.002 CVRu mm Hg−1 , respectively; P = 0.0004). An interaction was found between test day and astronaut presyncope (P = 0.005). Astronauts who could finish the 10-minute stand test had a significant reduction in their LF gain from preflight to landing and 3 days after landing; however, the nonfinishers had a significant increase in LF gain on landing day that was greater than the finisher group.

In the VLF range, females had an overall larger gain (0.039 ± 0.004 CVRu mm Hg−1 ) than males (0.022 ± 0.002 CVRu mm Hg−1 ; P = 0.03). Preflight, females had a larger supine VLF gain than males; on landing day, females had a higher VLF gain while standing compared to males (Figure 6). Males had a reduction in LF gain from preflight to landing and 3 days after landing. Males had lower LF gain than female astronauts on landing day and 3 days after landing (Figure 6). Both male and female astronauts had a significant main effect of a decrease in LF gain from supine to stand (P = 0.036); however, visual inspection of the data (Figure 6) would suggest that this was not the case on landing day. Astronauts who do not exhibit orthostatic intolerance after flight have normal cerebral autoregulation on landing day; however, there was a severe impairment of cerebral blood flow velocity regulation in astronauts with orthostatic intolerance after flight. Preflight, nonfinishers were operating at a higher resting cerebral blood flow velocity and similar mean supine blood pressure compared to finishers (Figure 1). On landing day, nonfinishers exhibited a large decrease in MFV associated with the same decline in BPMC A with standing as exhibited preflight. These results suggest that the cause of presyncope in astronauts may be linked with the loss of cardiovascular control of blood pressure and also may be related to a change in ability to autoregulate cerebral blood flow within the preflight blood pressure range. Preflight data (Figure 1) suggest that autoregulation characteristics of nonfinishers and finishers were different. MFV and conductance were much higher in the nonfinisher group in both the supine and standing positions. This could indicate that the nonfinishers were operating at a higher cerebral vasodilation for a given blood pressure. Although preflight BPMC A decreased from supine to stand, both finishers and nonfinishers had an increase in conductance, an appropriate response of a functional cerebral autoregulation system, and did not become presyncopal. Finishers had neither an increase nor a decrease in conductance with stand on landing day. The finishers also

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had an increase in supine MFV compared to preflight values but without an increase in conductance, which is a strong indication that this was driven by the increase in BPMC A (Figure 1) after flight and that autoregulation was operating at a new set point. The lack of increase in conductance with the decline in BPMC A with standing also suggests some impairment in autoregulatory function before flight, although this was not serious enough to precipitate symptoms of presyncope. In the nonfinishers, the decrease of landing day MFV with standing (Figure 1) was much greater than that of the finishers and those preflight. These data indicate that the nonfinishers were more severely challenged in terms of cerebral blood flow during stand than the finishers. This would indicate a severe impairment of cerebral autoregulation and may have precipitated presyncope in these astronauts. This can be seen in the sample landing day data from a nonfinisher (Figure 2); prolonged cerebral hypoperfusion attributable to loss of vasodilatory response (reduced blood flow) may be an important factor in the development of presyncope. A decrease in MCA conductance could be related to an increase in vascular stiffness, as seen in cerebral vessels after hind limb suspension in rats, or it could be that the cerebral vessels were close to maximal dilation and the decrease in MFV was directly attributable to the decline in blood pressure during standing.

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The current data on cardiac output and blood pressure in these astronauts indicate hypovolemia and, therefore, a decrease in cerebral volume during standing. However, with respect to space flight, it has been speculated that the head ward fluid shift causes vasodilation in the cerebral vessels, which may cause similar velocity latency on landing day. When plotted as a function of BPMCA ,the large decline of MFV on landing day in the nonfinishers is visible, as is the fact that this decrease occurred within the same blood pressure range seen before flight in both finishers and nonfinishers (Figure 3). This representation of data suggests a possible explanation of the change in autoregulation with space flight that is common between both finishers and nonfinishers, only with greater effect in the nonfinisher group; however, the steepness of the plateau region on landing day suggests a severe impairment or loss of autoregulation in this group. Female astronauts have different autoregulation characteristics, and on landing day females had reduced autoregulation compared to males. Astronaut gender may also play a role in susceptibility to orthostatic intolerance after flight. In this data set, 5 of 8 nonfinishers were female, whereas 17 of 19 finishers were male. A compilation of statistics (25 female, 140 male) on incidence of presyncope after short-duration space flight (5-16 days) showed a similar effect, with presyncope occurring in 28% of the females and in 7% of the males. The majority of cerebral autoregulation characteristics are similar between males and females; however, there are a few characteristics that are different and that may predispose females to orthostatic intolerance. These include differences in cerebral blood flow velocity and cerebrovascular reactivity. In this study, authors did observe higher cerebral blood flow velocity in females 3 days after flight, but not during preflight or on landing day (Figure 1). However, preflight VLF gain was double that of males (Figure 6) and reduced on landing day. This may indicate a reduction in autoregulation on landing day compared to that of males.

Venous Function during Long-Duration Spaceflights

In a standing posture, gravity induces peripheral venous pooling that, when excessive, can lead to orthostatic intolerance and fainting. For cosmonauts returning to Earth, the risk of orthostatic intolerance and fainting is greater in part due to hypovolemia resulting from adaptation to the microgravity environment. The purpose of the study was to use this method to assess venous function with long-duration spaceflight. Twenty-four male cosmonauts from the Russian space program were studied between 2009 and 2015 during spaceflights (124-192 days) aboard the International Space Station. Their mean ± SD anthropometric characteristics were as follows: age 44.3 ± 6.1 years, weight 82.6 ± 6.7 kg, height 1.77 ± 0.05 m, body mass index 26.4 ± 2.3 kg/m2 . Their physical activity was not controlled before flight but each performed 2 h of exercise daily aboard the International Space Station.

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Results One hundred and three plethysmography sessions were performed during this study (Table 1). Post-flight data were only collected on a small number of cosmonauts due to the late introduction of these measures into the study and operational limitations. Calf volume measures and venous plethysmography results for each testing day are presented in Table 1. Calf volume decreased during space flight and remained unchanged throughout the flight. Recovery to preflight volume began shortly after landing and was completed 8 days later. Absolute filling volume was not significantly altered during spaceflight or recovery from flight. However, relative to calf volume, venous filling significantly increased early during spaceflight and tended to remain elevated later in flight.

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Upon return to Earth, relative venous filling remained elevated on L0, but had recovered by L8. Venous distensibility, assessed through VFI, initially increased during the flight but recovered to pre-flight values later in flight. Following flight, VFI showed an exaggerated recovery on L0 and recovered to pre-flight values on L8.

Initial venous emptying (VER50%) was not significantly changed during or after spaceflight while the late venous emptying (VER90%) was decreased on the first flight session with a further decrease later in flight. Additionally, this parameter did not return to preflight levels on either L0 or L8. A slight increase in microvascular filtration was seen early in spaceflight but was not changed on any other testing day. All the venous filling parameters had the same pattern of changes during space flight that was different from the one of calf volume and venous emptying parameters. This pattern showed a large change during the initial part of the space flight and a trend toward recovery of pre-flight values during the second part of the space flight (Table 1). Calf volume showed a large change that was maintained during the whole space-flight while the venous emptying parameters showed continuously increasing changes (Table 1). The pattern of change was similar between venous filling parameters and microvascular filtration (Table 1). The results indicated alterations in venous functions with adaptation to microgravity. Changes were seen with both venous filling and emptying but different patterns in responses were noted that did not completely parallel changes in calf volume. Reduced calf volume leading to "bird legs" was noted in this study. However, upon return to Earth, venous function tended to recover after 8 days whereas muscle mass recovery requires additional time (6-8 weeks). Venous plethysmography demonstrated a decrease in VER90% that indicated a decrease in venous resistance. The decrease in venous resistance is also consistent with the overall vasorelaxation observed during space flight. This study demonstrated that both venous filling and emptying functions are altered during longduration spaceflight. While partially associated with changes in calf volume, the changes in venous function may indicate a redistribution of fluid unique to microgravity adaptations.

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Compression Garments as Countermeasures to Orthostatic Intolerance

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The ability to remain upright or egress from the space vehicle after landing may be compromised by an inability to maintain adequate arterial pressure and cerebral perfusion. Many astronauts experience postflight orthostatic intolerance, and its severity and incidence appear to increase as the length of microgravity exposure is extended.

Approximately 20-60% of astronauts returning from short-duration(4-18d) spaceflights and up to 83% of astronauts returning from long-duration (>1 mo) spaceflights become presyncopal during postflight orthostatic challenges. Reduced postflight plasma volume and altered distribution of blood while upright, particularly to the abdomen and lower body, is thought to contribute to postflight orthostatic intolerance. Orthostatic intolerance may be caused by an impaired ability to constrict the splanchnic vasculature. To provide protection against spaceflight-induced orthostatic intolerance during re-entry and landing, both NASA and the Russian Federal Space Agency require that astronauts and cosmonauts wear compression garments. During Space Shuttle landings, NASA astronauts used an inflatable antigravity suit (AGS) that consisted of five interconnected bladders that cover the abdomen, thigh, and calf. The bladders could be inflated to pressures ranging from 0.5 psi (25.9 mmHg) to 2.5 psi (129.3 mmHg) in increments of 0.5 psi. The purpose of this study was to evaluate a three-piece abdomen-high, elastic gradient compression garment (GCG) as a countermeasure to post-spaceflight orthostatic intolerance. There were 14 Space Shuttle astronauts (7 treatment, 7 controls) who volunteered to participate in this study. Astronauts participated in a short 3.5-min stand test before flight without compression garments as a measure of preflight baseline condition. Seven treatment astronauts (seven men, 47 ± 1 yr, 174 ± 2 cm, 83 ± 3 kg, mean ± SE; flight duration 12-16 d) completed the same stand test on landing day while wearing the compression garments. Seven astronauts (five men, two women,44 ± 2 yr, 178 ± 1 cm, 76 ± 3 kg, mean ± SE; flight duration 10-15 d) who completed an identical stand test in a separate study served as control subjects. Astronauts serving as control subjects did not wear the compression garments before or after flight. Approximately 30 d before launch (L-30) and on landing day, astronauts participated in a 3.5-min stand test.

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No astronauts wore the GCG during preflight testing and only the countermeasure subjects wore the GCG on landing day. Preflight testing was conducted in the Cardiovascular Laboratory at the Johnson Space Center, Houston, TX.

Postflight testing was conducted in the Baseline Data Collection Facility at the Kennedy Space Center, FL, or at the Dryden Flight Research Center, Edwards, CA. Testing on landing day was conducted approximately 2 h after wheel stop.

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Astronauts were instrumented to measure continuous ECG and beat-to-beat blood pressure in the finger during the stand test. The stand test began with the astronaut lying prone on a foam mat for 3 to 5 min. After baseline measurements were obtained, astronauts stood up as quickly as possible in response to a verbal cue, and stood quietly for 3.5 min (210 s).

During standing, the astronauts were discouraged from movement, muscle contractions, and talking (except to report symptoms), and were encouraged to breathe normally. Astronauts were asked to abstain from caffeine, nicotine, and alcohol for 12 h prior to testing, refrain from exercise within 4 h of testing, and avoid maximal exercise for 24 h prior to testing. Astronauts also were asked to avoid heavy meals in the 4 h prior to testing.

Abdomen, thigh, calf, and ankle circumferences were measured during each test session to measure changes in body segments that might influence the fit of the garments after spaceflight. Test operators also queried the astronauts regarding garment comfort and fit while the astronauts were wearing the garments on landing day. Astronauts scored the garment fit of the shorts and thigh stockings separately on a scale of 1 to 5, with 1 being "very comfortable" and 5 being "very uncomfortable". A score of 3 was considered to be "neutral"’. Result No subjects in either the GCG or control group became presyncopal during the 3.5-min stand test before or on landing day. Mean (± SE) heart rate and blood pressure values during prone rest and while standing for the GCG and control subjects are displayed in Table I. Mean (± SE) stroke volume, cardiac output, and total peripheral resistance values for the GCG subjects are shown in Table II . There was a significant Group × Time interaction (Z= -3.77, P <0.01) in subjects’ heart rate response to standing (Fig. 2). The postflight heart rate response to standing was not different from preflight in the GCG group [χ2 (1)=0.37,P=0.55], while the postflight heart rate response to standing was greater than preflight in the control group [χ2 (1)=7.08,P < 0.01]. The analysis of blood pressure revealed no significant effects; however, the data revealed somewhat lower overall systolic blood pressure among the controls relative to our GCG group (Z=1.87,P=0.06).

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GCG subjects’ total peripheral resistance response to standing was signifi cantly greater (Z= 2.32,P= 0.02) on landing day; however, stroke volume response was not significantly different on landing day (Z= -0.69,P=0.49). Calf, thigh, and abdominal circumference in GCG subjects were 1.7±0.8% (Z=-2.14,P=0.033), 2.4±1.0% (Z= -2.46,P= 0.014), and 2.6±0.9% (Z= -2.85,P= 0.004) lower, respectively, on landing day than preflight (Table III). The circumference of the ankle on landing day (-1.6±1.1%) was not significantly different (Z= -1.30,P= 0.193) than preflight.

The majority of the astronauts described the shorts and thigh-high garments as being comfortable on landing day. Specifically, five of the seven astronauts described the shorts as being comfortable or very comfortable, while two of the seven described them as being uncomfortable. Of the seven astronauts, six reported the thigh high garments as comfortable or very comfortable. The lowest comfort rating for the thigh-highs was 3, which would be neither comfortable nor uncomfortable "‘neutral"). None of the astronauts described the garments as being very uncomfortable.

The three-piece, abdomen-high compression garments effectively prevent post-spaceflight tachycardia, increase total peripheral response to standing, and are comfortable to wear. Tachycardia is a common finding after spaceflight and authors observed an elevated heart rate response to standing in the control subjects on landing day. However, the change in heart rate from prone to standing was similar from pre- to postflight in the GCG

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subjects. Also, stroke volume and cardiac output are normally reduced after spaceflight, likely due to decreased circulating blood volume, pooling in the lower extremities, or reduced cardiac effectiveness. In contrast, the decreases in stroke volume and cardiac output with standing after spaceflight were not different from preflight in astronauts who wore the three-piece GCG. Overall, the astronauts in the GCG group judged the three-piece compression garments to be comfortable to wear, even after completing the NASA standard fluid loading protocol.

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Evaluation of Compression Garments as Countermeasures to Orthostatic Intolerance (Compression_Garments) the NASA Anti-Gravity Suit (AGS) and the Russian Kentavr compression garment were effective countermeasures to orthostatic intolerance in subjects whose plasma volume was reduced pharmacologically to a similar degree as experienced by astronauts. While these compression garments were effective in these conditions, two observations led to the evaluation of other compression garments/conditions. First, although the AGS and Kentavr appeared to be equally effective in the initial study, the level of compression provided by the two garments were very different. The Kentavr provided compression of â&#x2C6;ź30 mmHg but the AGS was inflated to a pressure of â&#x2C6;ź78 mmHg. Thus, one objective of this study was to determine whether the AGS could provide a similar level of protection as the Kentavr when the AGS was inflated to provide a similar level of compression (â&#x2C6;ź26 mmHg). Second, astronauts have reported uncomfortable levels of abdominal compression while using the AGS, which may be particularly problematic after completing the pre-landing fluid loading protocol. Therefore, the second objective of this study was to determine the efficacy of a thigh-high compression garment, which might be more effective than either the AGS or the Kentavr because it provided a gradient compression to promote venous return. Both the AGS and Kentavr apply approximately the same level of compression across the entire length of the garment, but a commercially - available garment provides the highest pressure at the ankle, and the pressure decreases up the leg to the top of the thigh.

G-tolerance of female cosmonauts during descent in space flights of 8 up to 169 days in duration

The authors analyzed g-tolerance of female cosmonauts during descent in space flights based on the data about 4 female cosmonauts in 5 space flights The space flights were conventionally divided into short-term (8-16 days) and long-term (169 days). In two space flights (16 and 169-d long), tubeless anti-g suit Centaur was warn during descent. In these space flights, g-tolerance of females was quite satisfactory advocating for the possibility for women to fly to space without any constraints. When the anti-g suit was not used, female physiological systems were stressed heavier than male. The spacesuit smoothed away this difference. A distinct positive effect of wearing the anti-g suit by female cosmonauts during descent as it reduces stress to their physiological systems.

Tolerance of +Gz loads by space physician Poliakov VV during the active phases of his 438-days space mission

Tolerance of +Gz loads was assessed in space physician V.V. Polyakov during the active phases of his record, 438-day space mission. On the phases of insertion into orbit the +Gz-tolerance of the space physician was good; a fairly satisfactory g-tolerance during departure of orbit was extenuated by wearing of two anti-g suits (KARKAS-3 and CENTAUR) and administration of countermeasures against the unfavorable effects of space microgravity. His general health state and self-rating were not noticeably altered. +Gz loads in the course of descent from orbit instigated a syndrome characteristic of return to Earth from prolonged microgravity, i.e. a sensation of fierce pressure on the body, difficult breathing and speech, sine tachycardia, tachypnea, singular arrhythmias, petechial hemorrhage in the back integument, and vestibular/autonomous reactions. However, no evidence of any unusual physiological reactions that had never been seen in the other cosmonauts donned in the anti-g suits on earlier and less extended (from 65- to 366-day) missions were found. Extra systoles were registered on the phase of return to Earth after the 438-day but not previous 241-day mission of the space physician; they were probably associated with aging as he made his maiden flight at 47, and the second, at 53. The results speak in favor of the countermeasures against the adverse effects of microgravity applied during the mission, and the anti-g suits worn on the stage of return to Earth.

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Custom Gradient Compression Stockings May Prevent Orthostatic Intolerance in Astronauts After Space Flight,JSC-CN-22023,NASA.

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