ISOPTWPO Today

O CTOBER 2015, N O 21

ISOPTWPO Today, October 2015, No.21

ISOPTWPO Today

ISOPTWPO Today, October 2015, No.21

Cover Image Astronaut Stephanie D. Wilson NASA Image # : S97-10246 (19 June 1997) — Astronaut Stephanie D. Wilson, Mission Specialist

Biography Page Astronaut Stephanie D. Wilson NES Teachers Corner,NES Video Chat for Students - Astronaut Stephanie Wilson: Living and Working in Space NASA Explorer Schools is hosting a 45-minute live video chat for students in grades 4-12 on May 2, 2014, at 3 p.m. EDT. During the video chat, astronaut Stephanie Wilson will answer students’ questions about living and working in space. She was selected to become an astronaut in April 1996 and flew as a mission specialist astronaut on three shuttle missions. She has logged 42 days in space.

Image Credit: NASA Biography Background and Back Cover NASA astronaut Scott Kelly (@StationCDRKelly) captured this photograph of the green lights of the aurora from the International Space Station on Oct. 7, 2015. Sharing with his social media followers, Kelly wrote, "The daily morning dose of #aurora to help wake you up. GoodMorning from @Space_Station! #YearInSpace" Image Credit: NASA

2015, International Space Agency (ISA) ISOPTWPO TODAY First release, November 2013

Editorial Dear Reader It is my pleasure to introduce the ISOPTWPO. ISOPTWPO(International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office) is part of ISA, which support research on Human Space Flight and its complications.

The International Space Agency (ISA) was founded by Mr. Rick Dobson, Jr., a U.S. Navy Veteran, and established as a non-profit corporation for the purpose of advancing Man’s visionary quest to journey to other planets and the stars.

ISOPTWPO will research on NASA’S Human Research Roadmap. It will also research on long duration spaceflight and publish special issues on one year mission at ISS and twin study.

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Mr. Martin Cabaniss

Director Mr. Martin Cabaniss ISOPTWPO – International Space Agency(ISA) http: // www. international-space-agency. us/ Email:martin.cabaniss@international-space-agency.us

Editorial Dear Reader Hello, my name is Abhishek Kumar Sinha, and I am Assistant Director of the ISOPTWPO and editor of ISOPTWPO TODAY. Coinciding with the start of a new stage in International Space Agency’s history, ISOPTWPO TODAY returns with even greater momentum.

In articles covering ISOPTWPO research activities/findings , we have special features on NASA’S Human Research Roadmap, and the Risk of Orthostatic Intolerance During Re-Exposure to Gravity.

I hope you will enjoy the ISOPTWPO TODAY. Mr. Abhishek Kumar Sinha

Assistant Director Mr. Abhishek Kumar Sinha ISOPTWPO – International Space Agency(ISA) http: // www. international-space-agency. us/ Email:abhishek.kumar.sinha@international-space-agency.us

IN THIS EDITION Risk of Orthostatic Intolerance During Re-Exposure to Gravity (This is a reprint of article " Risk of Orthostatic Intolerance During Re-Exposure to Gravity " found at NASA’s Human Research Roadmap Website)

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Post-flight orthostatic intolerance, the inability to maintain blood pressure while in an upright position, is an established, spaceflight-related medical problem. Countermeasures have been identified and implemented with some success (exercise, fluid loading, compression garments). Completion of these efforts is essential for determining what preventive measures should be used to combat orthostatic intolerance during future mission profiles.

Post-spaceflight orthostatic intolerance remains a significant concern to NASA. In Space Shuttle missions, astronauts wore anti-gravity suits and liquid cooling garments to protect against orthostatic intolerance during re-entry and landing, but in-flight exercise and the end-of-mission fluid loading failed to protect ≈30% of Shuttle astronauts when these garments were not worn. The severity of the problem appears to be increased after long-duration space flight.

Five of six US astronauts could not complete a 10-minutes upright-posture tilt testing on landing day following 4-5 month stays aboard the Mir space station . The majority of these astronauts had experienced no problems of orthostatic intolerance following their shorter Shuttle flights. More recently, four of six US astronauts could not complete a tilt test on landing day following ≈6 month stays on the International Space Station . Similar observations were made in the Soviet and Russian space programs, such that some cosmonauts wear the Russian compression garments (Kentavr) up to 4 days after landing .

Future exploration missions, such as those to Mars or Near Earth Objects, will be long duration, and astronauts will be landing on planetary bodies with no ground-support teams. The occurrence of severe orthostatic hypotension could threaten the astronauts’ health and safety and success of the mission.

Risk of Orthostatic Intolerance During Re-Exposure to Gravity

Risk of Orthostatic Intolerance During Re-Exposure to Gravity

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Astronauts who have orthostatic intolerance are unable to maintain arterial pressure and cerebral perfusion during upright posture, and may experience presyncope or, ultimately, syncope. This may impair their ability to egress the vehicle after landing. This problem affects about 20-30% of crewmembers that fly short duration missions (4-18 days) (4-6) and 83% of astronauts that fly long duration missions when subjected to a stand or tilt test. Anecdotal reports, one documented by live media coverage, confirm that some astronauts have difficulty with everyday activities such as press conferences, showering, using the restroom or ambulating after a meal.

The etiology of orthostatic intolerance is complicated and multifactorial, as shown in Figure 1. While the decrease in plasma volume, secondary to the headward fluid shift that occurs in space, is an important initiating event in the etiology of orthostatic intolerance, it is the downstream effects and the physiological responses (or lack thereof) that may lead to orthostatic intolerance. This is highlighted by the fact that while all crewmembers that have been tested are hypovolemic on landing day, only a fraction of them develop orthostatic intolerance during stand/tilt testing.

One physiological mechanism that has been shown to contribute to post-spaceflight orthostatic intolerance is dysfunction of the sympathetic nervous system , with or without failure of the renin-angiotensin-aldosterone system . These two control systems are activated with postural changes to the upright position. As central blood volume pools in the lower extremities, aortic-carotid baroreceptors are stimulated by low blood pressure (BP), and cardiopulmonary baroreceptors are stimulated by low blood volume. The baroreflex response via the aortic-carotid pathway is to stimulate the sympathetic nervous system to release norepinephrine, which causes systemic vasoconstriction and increases cardiac contractility, thereby maintaining blood pressure. The baroreflex response via the cardiopulmonary pathway is to stimulate the reninangiotensin- aldosterone system which causes sodium and water reabsorption to maintain central blood volume and blood pressure. If the sympathetic nervous system and/or renin-angiotensin-aldosterone system are inhibited, orthostatic intolerance may occur.

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity Another possible mechanism for post-spaceflight orthostatic hypotension is cardiac atrophy and the resulting decrease in stroke volume (SV), as has been shown in multiple bed rest studies and a flight study .

Stroke volume is easily altered by mechanical and hydrostatic effects and serves as the primary stimulus to baroreflex regulation of arterial pressure during an orthostatic stress as part of the "triple product" of blood pressure control: BP = HR (heart rate) X SV X TPR (total peripheral resistance). Orthostatic hypotension will ensue if the fall in stroke volume is of sufficient magnitude to overwhelm normal compensatory mechanisms or if the reflex increase in HR and/or TPR is impaired by disease states or by a specific adaptation of the autonomic nervous system.

After adaptation to real or simulated microgravity, virtually all individuals studied have an excessive fall in stroke volume in the upright position . Although there are conflicting data regarding changes in baroreflex regulation of heart rate and vascular resistance that may limit the compensatory response to orthostasis , it may be this excessive fall in stroke volume that is the critical factor of microgravity induced orthostatic hypotension.

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While orthostatic intolerance is perhaps the most comprehensively studied cardiovascular effect of spaceflight, the mechanisms are not well understood. Enough is known to allow for the implementation of some countermeasures, yet none of these countermeasures alone has been completely successful at eliminating spaceflightinduced orthostatic intolerance following spaceflight. The combination of multiple countermeasures (fluid loading, re-entry compression garments and post-landing compression garments) and immediate access to medical care has been successful at controlling this risk for short duration flights. Once the post-landing garments have been validated following long duration flights, it is likely that this risk will also be controlled.

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity

Locomotor Dysfunction and Recovery of Function after Long-Duration Space Flight Exposure to the microgravity conditions of space flight induces adaptive modification in sensorimotor function.

Upon return to Earth’s 1-g environment, these modifications cause various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Early studies investigating the effects of space flight on locomotor control showed that after space flight,subjects tend to exhibit a stamping gait, drift off the intended path, raise their arms to the side frequently, take small irregularly spaced steps for greater stability, and adopt a wide base of support.

More recent studies of changes in locomotor function after space flight have documented changes in speed while walking around corners, significant modifications in the spatial and temporal features of muscle activation and increased within - day activation variability, increased variability in ankle and knee joint motion, alterations in head-trunk control, and alterations in ability to coordinate effective landing strategies during jump tasks.

Astronauts returning from space flight and performing Earth-bound activities must rapidly transition from one sensorimotor state to another. For returning crewmembers, the rate of recovery of sensorimotor function varies, as crewmembers evoke different recovery mechanisms to re-adapt.

Early Russian investigations studying the effects of 2-30 days of space flight on locomotor control showed that the post-flight performance decrements were related in most cases to the length of the flight and performance recovered, on average, within 2 days and in most cases within 2 weeks. The magnitude and time course of balance control recovery during standing was investigated using a clinical posturography system (Equitest, Neurocom International) on astronauts returning from Space Shuttle missions ranging from 5 to 13 days.

These investigations found that the recovery time course followed a double exponential path with a rapid improvement in stability during the first 8-10 h followed by a more gradual return to pre-flight stability levels over the next 4-8 days. In a previous study authors reported a reduction in compensatory head pitch movements during post-flight locomotion followed by a recovery trend spanning 6-10 days in crewmembers returning from missions to the MIR space station after 4-6 months.

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity Courtine and Pozzo (2004) investigated the spatial and temporal patterns of head and trunk movements of cosmonauts walking over ground, ascending stairs, and jumping down from a platform after returning from space flight that lasted 6 months. They reported that 2 days after returning from long-duration space flight subjects held their heads at significantly lower positions in the pitch plane than pre-flight, but head stability did not change, and coordination patterns between head and trunk segments were not disrupted. Importantly, all the variables that showed gait disruptions had recovered to pre-flight levels by 6 days after their return from space flight.

The goal of this investigation was to assess locomotor dysfunction and recovery of function after long-duration space flight using a functional task that consists of traversing an obstacle-avoidance course. This functional mobility test (FMT) was designed to provide information on the functional implications of post-flight locomotor dysfunction. The primary outcome measure studied was the time to complete the course (TCC, in seconds). Here, authors quantify subjects’ recovery of performance and the learning processes involved during re-adaptation in functional mobility after long-duration space flight.

Eighteen International Space Station crewmembers experiencing an average flight duration of 185 days performed the functional mobility test (FMT) pre-flight and postflight.They included 17 males, 1 female, mean age 46 years (range 37-54 years). Fourteen subjects had prior space flight experience. All subjects gave informed consent according to the requirements of the Committee for the Protection of Human Subjects at NASA Johnson Space Center. To perform the FMT, subjects walked at a self selected pace through an obstacle course consisting of several pylons and obstacles set up on a base of 10-cmthick, medium-density foam for a total of six trials per test session.

Functional Mobility Test In the FMT, crewmembers were required to navigate an obstacle course set up on a base of 10cm -thick, medium density foam (Sunmate Foam, Dynamic Systems, Inc., Leicester, NC, USA), as shown in Fig. 1. The compliant foam changes continually as the individual stands on it, making the support surface unreliable. The foam was used to make proprioceptive information unreliable during ambulation. It had an added benefit for safety: if anyone had fallen it would have provided a soft landing.

The 6.0 m X 4.0 m course consisted of the following obstacles: (1)Five foam pylons arranged in a "slalom" fashion hung from the ceiling, which required the subject to change heading direction continuously.

(2)A gate with edges defined using two foam pylons hung from the ceiling, the width of which was adjusted to the width of the crewmember’s shoulders, so they had to walk between the pylons "sideways".

(3)A 46-cm high Styrofoam block placed on the foam surface which forced the crew member to balance on one foot on an unstable surface (foam) while clearing the obstacle.

(4)A "portal" constructed of two successive 31-cm high Styrofoam blocks placed on the foam surface, with a horizontal foam bar hung from the ceiling between these blocks, the height of which was adjusted to that of the crewmember’s shoulders requiring crewmembers to bend at the waist or lower themselves to avoid hitting the bar hung from the ceiling and balance on a single foot on a compliant surface while stepping over the barrier.

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FMT trial procedures In each test session crewmembers were instructed to "walk as quickly and as safely as possible without running or touching any of the obstacles on the course". This task was performed three times in the clockwise direction and three times in the counterclockwise direction in a randomized order.

Subjects were allowed to rest between trials, especially immediately after flight, and all six trials were completed within a 10-min window.

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To prevent injury from falling, in addition to the medium-density foam on the floor, subjects wore a harness while being monitored by a "spotter." The spotter walked near the subjects (especially post-flight), ready to grab them by the harness straps to ensure their safety during all phases of the experiment.After a verbal "ready" indication, subjects began to walk the course.

The primary outcome studied was the time (in seconds) to complete the course (TCC), regardless of whether contact was or was not made with the obstacles.

Results Magnitude of dysfunction in FMT Figure 2 shows the trend lines of first-trial TCC preflight and 1 day after return for the 16 subjects with data from both sessions. Throughout the sessions, subjects were usually able to avoid the obstacles. One subject failed to avoid obstacles twice in a session 1 day after return. In all other sessions, pre- and post-flight, subjects were able to completely avoid obstacles, or failed to avoid only once. All of our subjects completed the FMT task without falling. All crewmembers exhibit altered locomotor function after long-duration space flight, with a median 48% increase in the time to complete the FMT course.

Recovery of function in FMT Figure 3 shows estimated values of the median, middle 50%, and middle 95% of the distribution of TCC for preflight sessions and as a function of time after landing for post-flight sessions, overlaid with a plot of actual log TCC values. The percentiles of the TCC distribution were obtained empirically by using the fitted model to simulate data from 10,000 hypothetical "subjects" performing the FMT at the same time points as in the actual study. Figure 3 suggests that the model’s trend and variability described the actual data quite well. Note that only seven of the total 103 data points (6.8%), and six of 83 (7.1%) postflight data points fall outside of the 95% intervals. Two subjects were excluded from consideration when estimating the covariance of the random effects parameters.

Examination of the raw data for these subjects revealed a slight increase in TCC after flight with no clear improvement trend; hence, an exponential recovery model could not be reliably fit to these data.

Figure 4 shows the fraction of the astronauts that would be expected to attain a certain percentage of recovery t days after landing. We expect that immediately post-flight most astronauts would experience some deficit in performance resulting in increased FMT transit times relative to their pre-flight levels.

Authors define percent recovery to be the percent of this (subject-specific) deficit that is made up over time.

Thus, by definition, subjects are 0% recovered at t = 0, and are 100% recovered when their transit times reach pre-flight levels. From the fitted model we calculated that a typical subject (solid line in middle of gray area) would recover to 95% of his/her pre-flight level at approximately 15 days post-flight.

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Motor control strategies in recovery Figure 5a shows a scatter plot of a single crewmember’s TCC-values for all trials on each session during the different days of post-flight testing. The horizontal line is the crewmember’s average TCC for the last pre-flight session, while the dashed curve illustrates the fit to the first trial TCC across post-flight sessions. This crewmember essentially recovered to his/her pre-flight level within 7 days. Note also that a distinct improvement in performance is seen over the trials within each day of testing. Figure 5b shows the exploded view of this person’s TCC values both pre-flight and on 1 day after return from space flight, with separate fits to Eq. 3 (dashed curves).

The results of the study indicated that over the 16 individual subjects who could complete the FMT 1 day post-flight, there was a median increase of 48% in TCC relative to pre-flight 1 day after their return. All subjects appeared to perform the FMT task by trading speed with obstacle avoidance or balance maintenance during the post-flight recovery period as compared to pre-flight. Authors estimated that the time for a typical subject to achieve 95% recovery of FMT performance after long-duration space flight would be approximately 15 days.

Locomotion is a complex task, demanding coordination of the eye-head, head-trunk and lower limb locomotor apparatus. Goal-directed locomotion, as was tested using the FMT, required subjects to trade off their walking speed with their ability to maintain equilibrium and coordination while negotiating the obstacles. Negotiating the obstacles on the course required modifying the heading direction to avoid hitting the pylons, bending at the waist or lowering themselves to avoid hitting the horizontal bar hung from the ceiling and stepping over obstacles and balancing on a single foot to step through the portal, and using equilibrium skills to maintain balance on the compliant surface. Further, walking on the foam surface increases the instability of the upper body as compared to a solid surface and increases the reliance on vestibular derived information.

Reports on astronauts’ responses during adaptation of illusory self motion and the simultaneous compensation for these motions when viewing a rotating display of dots on the inside of a rotating drum, or vertical optokinetic stimulation in microgravity suggest that reliance on visual cues is increased and on graviceptor signals is reduced.

In some astronauts local tactile cues from bungee cordinduced foot pressure inhibited visually induced motion illusions . More recent work has shown that astronauts in microgravity become more dependent on dynamic visual and proprioceptive cues as well as static visual orientation cues. These illusions of self motion continue to be reported during reentry and immediately after landing in response to voluntary pitch or roll head movements or passive roll stimulation in darkness immediately after landing .

Adaptation to microgravity results in lack of bipedal balance control under post-flight test conditions requiring accurate feedback from the vestibular inputs and ankle proprioception on computerized dynamic posturography. Most of the subjects had increased reliance on feedback from vision during their recovery process as a result of degraded performance of the other two feedback systems during adaptation to microgravity.

Proprioceptive function also adapts to microgravity, as reported by Roll et al., causing the reduction in relevance and coding of proprioceptive inputs during standing posture and body movements, and enhanced reports of movement illusions in response to tendon vibrations. Therefore, adaptation to microgravity causes a different combination of reliance on visual, proprioceptive and vestibular cues underlying sensorimotor processing of body orientation and posture post-flight.

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Also, previous work has shown that after space flight astronauts experienced sensorimotor changes indicated by changes in spinal circuitry function: altered H, otolith-spinal and stretch reflex characteristics, modifications in proprioceptive functioning, and loss in muscle strength and tone. All of these changes may have contributed to the change in subjects’ post-flight FMT performance.

The recovery of physiological function after space flight has been measured in several systems individually, showing a wide range of recovery times. Studies show otolith receptors recovering after a day , the neuromuscular complex recovering in 1-3 weeks , and bone tissues taking up to several months.

In a study Courtine and Pozzo reported that near optimal locomotor abilities were restored in subjects when they were tested on complex tasks on the sixth day after their return from long-duration space flight.

This difference from our findings in the present study may be due to differences in the task requirements of the two tests.

Motor control strategies in recovery The results of the present study also show that postflight recovery can be divided into two processes: rapid strategic learning over the six trials on the first day after return, and a slower process taking over 2 weeks to recover to a pre-flight level of functional performance.

The individual subjects’ short-term learning parameters over the first post-flight trials and their longterm recovery parameters across sessions were significantly positively associated. Several studies have examined the time course of motor learning in different training paradigms such as a visual discrimination task or while learning to adapt to distortions either visual or mechanical.

The time course of motor learning has been described to occur in two stages: (1)A fast, within-session improvement that can be induced by a limited number of trials on a time scale of minutes .

(2)A slowly evolving, incremental performance gain, triggered by practice but taking hours to become effective .

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These two learning processes for motor adaptation to sensory discordances have also been described as strategic control versus adaptive realignment (referred to as "adaptation"), respectively.

In support of the concept that two processes control adaptation, recent studies have shown that motor adaptation is driven by two distinct neural systems that differ from each other in terms of their sensitivity to error and their rates of retention . Separate neural substrates have also been shown to control the execution of these two motor strategies. Pisella et al. (2004) reported that a patient with a bilateral lesion of the posterior parietal cortex (PPC) was not able to implement on-line strategic adjustments in response to a prismatic shift in visual feedback during a pointing task, yet showed adaptive after-effects. The authors contended that the strategic component was linked to the posterior parietal cortex, and the adaptive component was linked to the cerebellum. Anguera et al. have further showed that cognitive processes such as spatial working memory contributed to the early and not the late stage of motor learning by comparing the rates of adaptation and overlap of the neural substrates of this cognitive and the two motor learning stages during a visuomotor adaptation task. Thus, authors contend that these two distinct motor learning stages can influence the rate of post-flight recovery while readapting to Earth’s gravity.

Spaceflight-induced cardiovascular changes Microgravity exposure induces physiologic adaptations in astronauts such as sensorimotor disturbances, cardiovascular deconditioning, and loss of muscle strength and muscle mass.Though these physiologic alterations have been studied individually, their collective impact on crewmembers’ performance during mission - critical tasks upon return to a gravity environment has yet to be determined.

The Functional Task Test aims to: (1) identify the critical mission tasks that may be impacted by alterations in physiologic responses; (2) map physiologic changes to alterations in functional performance; (3) aid in the design of countermeasures that specifically target the physiologic systems responsible for impaired functional performance.

The Recovery from Fall/Stand Test simulates one such task, measuring the ability to stand up from a prone position and the cardiovascular response to orthostasis.

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 (7) ladder climb.

The seat egress and walk, recovery from fall/stand test, and torque gen-eration have multiple components, each of which was analyzed separately for a total of 11 tasks (Table 1).

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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.

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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 suppressed 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.

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Heart rate 30 days after landing was not different from preflight during any of the tasks.

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There were two key findings in this work: (1) changes in autonomic activity historically observed in 5 to 10 minute stand and tilt tests were detected during a 3 minute stand test without a prior stabilization period, and (2) the postflight 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 we were able to identify spaceflight-induced autonomic dysfunction during the Recovery from Fall/Stand Test. Parasympathetic modulation was diminished postflight, 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 postflight and remained decreased 8-10 days after landing even though Eckberg found the vagally mediated baroreflex to have returned to preflight 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, our index of sympathovagal balance, has been previously observed to be higher than preflight levels up to 4 days after landing . Sympathetic activity upon landing has been reported to not be different from preflight values, yet most studies conclude sympathetic activity is increased by spaceflight . SBP LF, our 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 preflight (7±2 mmHg2 , 22± 8 mmHg2 ), and authors speculate that if we 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 preflight 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. The spectral heart rate variability analysis requirements of stationarity and data length cannot be met during most of the functional tasks due to subject movement and short task duration.

Yet, from heart rate variability analysis during the stand test, authors see that the elevated heart rate postflight is likely due to diminished parasympathetic modulation. Results from the Recovery from Fall/Stand Test could provide more insight into the cause of the elevated heart rate during the functional tasks after spaceflight through the examination of spectral indices of autonomic modulation during prone and stand since the other

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functional tasks do not meet stationarity and length requirements for spectral analysis. The Functional Task Test aims to detect changes in performance during simulations of mission-critical tasks and correlate these changes to physiologic variables. Authors were able to detect spaceflight-induced cardiovascular deconditioning during such tasks, where the increased heart rate was still evident during most tasks 6 days after returning to Earth.

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Orthostatic Hypotension: Mechanisms, Causes, Management Orthostatic intolerance refers to the development of symptoms such as lightheadedness and blurred vision when a subject stands up that clears on sitting back down. Other symptoms include cognitive blunting, tiredness, and head and neck ache. These symptoms are due to cerebral hypoperfusion. The posterior head and neck ache (with a coathanger distribution) is thought to be due to ischemia of large neck muscles. Other symptoms such as palpitations, tremulousness, nausea, and vasomotor changes are due to sympathetic hyperactivity and occur in patients with only partial autonomic failure.

Common causes of orthostatic intolerance are shown in Table 1. A common cause of transient orthostatic intolerance is reflex syncope (vasovagal, vasodepressor). An otherwise normal person suddenly faints. Vasovagal and vasodepressor syncope are both characterized by the sudden abrupt fall in blood pressure (BP). They differ in that in vasovagal syncope, the abrupt fall in BP, is accompanied by a similarly abrupt fall in heart rate whereas the latter is absent in vasodepressor syncope. They are often triggered by pain (such as receiving an injection or blood-draw) or emotional stimulus. These occur in persons with normal baroreflexes and occur suddenly. Another cause, occurring about 5-10 times as commonly as OH, is postural tachycardia syndrome, characterized by orthostatic intolerance coupled with orthostatic tachycardia. OH is defined as a reduction of systolic BP of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing up.

The "prevalence" of OH increases with age and occurs in 10-30% of elderly persons. There is a moderate spread in reported frequency of OH (Table 2). Although the values are not population based, and therefore not true prevalences, the numbers are pragmatically important. They make the point that OH in the elderly is common.

BP control becomes progressively more impaired with aging, due to a multitude of reasons including impaired baroreflex sensitivity, volume status, and venomotor tone.

Part of the explanation resides in the increased occurrence of associated conditions like diabetes and Parkinsonâ&#x20AC;&#x2122;s disease as well as the effects of drugs like anti-hypertensive agents, diuretics, and antiParkinsonian drugs like levodopa. The presence of OH is associated with increased mortality and morbidity. The reason for the increase in morbidity and mortality is multifold but includes the consequences of repeated falls, resulting in fractures, head injury, and their complications.The normal human subject maintains the same BP supine and standing. This maintenance of postural normotension depends on a normal plasma volume, intact baroreflexes, and reasonable venomotor tone. A subject with reduced plasma volume (hypovolemia) can develop OH. Similarly, OH can occur in some subjects (predisposed to OH) because of excessive venous pooling. The splanchnic mesenteric bed is especially important

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because of its large volume and baroreflex 200-300% after a meal and this increased venous capacitance causes venous pooling with resultant post-prandial OH in predisposed subjects.

Standing in normal subjects results in a fall in blood and pulse pressure and this fall is sensed by baroreceptors in carotid sinus and aortic arch. Baroreceptor afferents synapse at the nucleus of the tractus solitaries (Fig. 1). The vagal baroreflex pathway runs from the nucleus of the tractus solitarius to the nucleus ambiguus and sends efferents to the sinoatrial node to increase heart rate. The adrenergic baroreflex pathway runs from the nucleus of the tractus solitarius to the caudal ventrolateral medulla and from there to the rostral ventrolateral medulla. The adrenergic pathway continues with sympathetic efferents from the rostral ventrolateral medulla to the interomediolateral column of the thoracic spinal cord, and from there to autonomic ganglia and to the heart, arterioles, and venules. Hence, the initial fall in BP is corrected by an increase in HR and total systemic resistance. If the baroreflexes fail, as in adrenergic autonomic failure, there are several consequences.

There is: • OH. • Supine hypertension (since baroreflexes also prevent excessive BP increase).

• Loss of diurnal BP variation. The normal subject has lower nocturnal BP. Patients with baroreflex failure have unchanged or higher nocturnal BP. Causes of orthostatic hypotension There are many causes of OH (Table 3). Most cases seen in clinical practice are best divided into those with and without CNS involvement. Patients with CNS involvement can be separated into those with brain or spinal cord disease. Patients with chronic OH without CNS involvement will most commonly have OH due to diabetes. Less likely causes are amyloid, either sporadic or inherited (tranthyretin mutation), autoimmune, or paraneoplastic etiology.

Some have no cause found and are typically designated as idiopathic OH or pure autonomic failure. If they have dream enactment behavior, they are best designated pure autonomic failure, since they likely have a synucleinopathy. In a setting of acute onset of OH, the main considerations are Guillain-Barre syndrome, where the diagnosis is usually obvious because of severe motor weakness, respiratory compromise, and acute autoimmune autonomic neuropathy ("acute pandysautonomia"). The latter is characterized by severe and generalized autonomic failure without prominent motor or sensory involvement.

Other causes such as botulism, porphyria, or those due to toxic causes are uncommon. Their consideration comes up if there is an acute autonomic neuropathy that is undiagnosed and especially if there are red flags for these diseases. In such circumstances, tests such as urine drug and heavy metal screen, tests for porphyria, botulism, and paraneoplastic panel are done.

Chronic causes of OH are much more common than acute causes. The most common cause is mild OH due to old age. For patients with brain involvement, OH is common in Parkinson’s disease, occurring in 20-40 percent of patients, but is usually mild. More severe OH occurs in patients with multiple system atrophy or Lewy

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body dementia. Patients with alcoholic neuropathy usually do not have OH and those who have florid OH often have Wernicke- Korsakoff syndrome, with involvement of brain stem autonomic structures. Patients with baroreflex failure, as occurs in neck radiation or familial dysautonomia, can have OH, but this symptom is mild compared with autonomic storms, due to de-afferentation.

Most forms of olivopontocerebellar atrophies do not have OH and patients with chronic cerebellar involvement and OH should raise suspicion of the cerebellar subtype of MSA (MSA-C).

Drugs Midodrine is a directly acting Îą1-adrenoceptor agonist. It and its active metabolite, desglymidodrine, have a duration of action of 2-4 hours.

The main side-effects are supine hypertension, paresthesias (including troublesome scalp-tingling), and goose-bumps. Rarely patients develop bladder pain or an inability to void, problems that preclude use of midodrine in those patients.

Fludrocortisone expands plasma volume and increases sensitivity of Îą-adrenoceptors. It is usually used at a dose of 0.1-0.2 mg/day. Main complications are hypokalemia and supine hypertension.

Droxidopa, an oral norepinephrine precursor, was shown in a phase III treatment trial to improve symptoms and improve standing systolic BP. The drug was recently approved by the FDA for rare diseases with OH. Droxidopa is generally well tolerated. It seems to have a duration of action of about 6-8 hours.

Currently, midodrine remains the preferred drug. It could potentially be preferable for patients who do not tolerate midodrine or who find its duration of action unacceptably short. Patients with dopamine beta-hydroxylase deficiency seem to have better BP control with droxidopa than midodrine.

Pyridostigmine, a cholinesterase inhibitor, will improve standing BP in patients with OH without aggravating supine hypertension. This action occurs since baroreflex unloading occurs on standing and is minimal at rest. Cholinesterase inhibition increases the safety factor of ganglionic transmission by delaying breakdown of acetylcholine. The main limitation of pyridostigmine is its modest effect.

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D ID YOU KNOW ?

A LTERNATIVE C OMPRESSION G ARMENT (ACG)

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Following space flight, the ability to remain upright (standing) 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 percent of astronauts returning from short duration space flights (418 days) and up to 83% of astronauts returning from long duration space flights (greater than one month) become presyncopal during postflight orthostatic challenges. Reduced postflight plasma volume and altered distribution of blood, particularly to the abdomen and lower body, while upright is thought to contribute to postflight orthostatic intolerance.

To provide protection against space flight-induced orthostatic intolerance during reentry 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 Russian Kentavr is a non-inflatable compression garment made of a resilient elastic fabric. It consists of bicycle-type shorts that extend to the knee and a pair of gaiters that cover the calves. Each component of the Kentavr has lacing to allow adjustments, and the optimal pressure produced by the Kentavr is 30 Âą 5 mmHg. One disadvantage of the Kentavr is that uncovered areas of the body (e.g. knees, ankle, and feet) tend to swell if the garment is worn for an extended period of time, such as when cosmonauts continue to wear the Kentavr as they readapt to Earth gravity in the first few days following flight.

Due to the limitations of the AGS and Kenavr, the investigators initiated a series of studies to evaluate the efficacy of various configurations of compression garments with the intent of identifying a new garment which could be integrated into advanced exploration suits with little to no complication. BSN-Medical, Inc. manufactures commercial-off-the-shelf and custom-fit compression garments that are available in a variety of styles and pressures. The garments are made from a blend of nylon and spandex to provide mechanical compression and are used clinically to treat vascular disorders and orthostatic hypotension. Working with materials experts at BSN-Medical, Inc. the investigators developed individually-fitted, abdomen-high compression garments which were custom-designed to combine the positive features of the AGS and Kentavr, while eliminating most of the negative features.

These garments provide a gradient compression along the length of the leg rather than static pressures; do not require a pressurized air source from the vehicle or other external source; provide complete coverage from the toes to the abdomen so as to prevent uncomfortable swelling in tissue in the uncompressed areas as in other garments; and do not increase the physical effort associated with ambulation experienced while wearing the AGS. Furthermore, these lightweight piece garments are easy to don, relatively inexpensive to produce, and require minimal stowage and maintenance in flight.

Reference:

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Stenger MB, Lee SMC, Westby CM, Ribeiro LC, Phillips TR, and Platts SH. Abdomen-high elastic gradient compression garments during post-spaceflight stand tests. Aviation, Space, and Environmental Medicine.

2013. 84:459-466.

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Changes in Toe Clearance During Treadmill Walking After Long-Duration Spaceflight Toe Trajectory during the swing phase of locomotion is characterized as a precise motor control task involving the joints and muscles on the stance and swing limbs, thus giving a composite metric for the effectiveness of the control task.The study of toe trajectory (more specifically toe clearance) is often used to determine tripping potential while walking or stepping over an obstacle. Subjects with pathologies or compromised gait may exhibit altered toe trajectories - which increases their chances of tripping - despite attempts to compensate with novel motor-control strategies in the lower limbs.

The toe is the end-effector of a seven-segment kinematic chain, and its position depends on the joint angles along this chain. Winter showed how small changes in individual lower-limb joint angles (ranging from 0.86 to 3.3◦ ) could account for the observed variability in toe clearance. Specifically, toe clearance was most sensitive to variation in the pelvis roll and swing leg knee flexion angles. Others have reported that toe position is fine-tuned by the adjacent ankle joint and is responsive to its kinematics.

Given the dependence of toe position on the kinematics of proximal joints and segments, it follows that any condition that may increase walking variability could affect toe trajectory and subsequently may increase the likelihood of a trip and fall. One such condition would be returning from long-duration spaceflight, where one must readapt to Earth’s gravity from a microgravity adapted state.

Astronauts experience many physiologic changes caused by spaceflight, especially in the neurovestibular and sensorimotor systems. These impairments may interfere with crewmembers’ ability to function efficiently as they readapt to the gravitational environment upon return to Earth (or upon landing on the Moon or Mars), possibly compromising mission objectives or delaying timelines, or more importantly, posing a danger to the crewmember in an emergency scenario.

These symptoms also lead to a slower, more cautious gait and other locomotor difficulties. Specifically during walking, control of the leg may be compromised immediately after landing because of decreased muscle strength , the crewmembers’ reported feeling of " heavy limbs ", changes in leg muscle activation variability, an altered malleolus path during swing, and increased variability of lower limb joint angles. These may lead to greater toe clearance variability, especially given its sensitivity to small changes in leg joint angles. No study to date has examined the effects of spaceflight on toe trajectory during walking and its relation to an increased risk of tripping.

Ten crewmembers (mean age ± SD: 46.0 ± 5.6 yr) from five missions aboard the International Space Station (ISS) provided written informed consent before participating in this study. The study protocol was approved in advance by the NASA Lyndon B. Johnson Space Center (NASA JSC) Committee for the Protection of Human Subjects. Subjects spent an average of 188 ± 6 d in space, which includes time spent on the ISS and in the transport vehicles.

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Results The mixed-model evaluation of the data from all trials revealed that none of the toe clearance medians in the postflight sessions were significantly different than preflight, except for the long-range follow-up session ( P = 0.01; Fig. 2A ). Notable differences in the median vs. preflight were seen at 2 d and 3 to 4 d postflight(P =0.08 and P = 0.10, respectively).

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Further, this model revealed that our first-trial indicator variable was significant ( P < 0.001), suggesting that results for participantsâ&#x20AC;&#x2122; first trial were different from subsequent trials. Follow-up models focusing only on data from the first trial of each session showed that median toe clearance was not significantly different in any of the postflight sessions, and the trend of the changes over time was qualitatively similar as that of the alltrials analysis. Like the all-trials analysis, the difference in the median from preflight at 3 to 4 d postflight was notable ( P = 0.06), but the difference at 2 d postflight was not ( P = 0.12).

For interquartile range (IQR), the mixed-model regression again showed that the first trial was a significant effect(P < 0.001). However, in both the all-trial and first-trial-only models, the toe clearance IQR for each postflight session was not significantly different than preflight (Fig. 2B).Notable differences from preflight were found for the IQR at 6-7 d postflight(P = 0.10) in the alltrials model and at 2 d postflight ( P = 0.09) in the first-trial-only model. The trend in IQR over time was similar in both analyses.

An examination of landing day data showed that one subject (Subject 02) had a lower median toe clearance across trials than before flight ( Fig. 3A ). Inspection of toe clearance IQRs on landing day showed one subject (Subject 05) with an increased IQR compared to preflight( Fig. 3B ). Subject 07 completed only one trial on landing day, so an overall trend cannot be confidently determined. Since the first trial indicator was significant in the main analysis, the data points representing the first trials at each time point were examined as well (see dashed lines in Fig. 3 ). Subjects 02 and 07 walked with a reduced median toe clearance during the first trial just after landing, and the median returned to the preflight level after 1 d. The toe clearance IQR for the first trial of Subject 05 after landing was greater than preflight, while the IQRs for the fi rst trials of Subjects 02 and 07 were slightly decreased compared to preflight.

Extending the median toe clearance data for the landing day subjects (Fig. 4), three characteristics could be noted in the curves. First, the lines connecting all of the first trial medians showed that most of the greatest medians at each time point were from the first trials. Secondly, all three subjects walked with an increased toe clearance at day 3-4 compared to preflight. Finally, the medians of all three of these crewmembers returned to their respective preflight values by their final session, whether that was 11 - 30 d postflight (two subjects) or the 6-mo follow-up session (one subject).

The Somerâ&#x20AC;&#x2122;s d correlation analysis ( Table II) revealed a significant negative association between changes in foot pitch angle (versus preflight) and toe clearance changes (versus preflight P < 0.04) in the first-trial-only analysis. In other words, a positive change in foot pitch(" toes-down ") caused a negative change in toe clearance(closer to the floor). A notable negative association between foot pitch angle changes and toe clearance changes( P = 0.06) was observed in the analysis of the remaining trials. There were significant positive associations among changes in both ankle dorsifl exion angle and pelvis roll angle and changes in toe clearance for both the first trial-only analysis ( P = 0.01 and P < 0.01, respectively) and for the remaining three trials ( P <

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0.01 for both). Hip fl exion may have been correlated with toe clearance in the analysis of the remaining three trials ( P = 0.10), but it was non significant in the first-trial-only analysis( P = 0.45).

In this retrospective study, authors sought to determine whether astronauts were at an increased risk of tripping after their return from long-duration (6 mo) spaceflight by tracking pre- to postflight changes in toe clearance

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity when crewmembers walked on a treadmill while performing a dynamic visual acuity task. Of the crewmembers available on landing day, one exhibited a decreased median toe clearance with no change in IQR compared to preflight, while another subject showed no change in median toe clearance but with a marked increase in IQR compared to preflight. For all subjects, both median toe clearance and toe clearance IQR were not significantly different from preflight levels at all postflight time points after landing day, with the exception of the median toe clearance at the 6-mo follow-up session. However a notable, but nonsignificant, increase in median toe clearance was observed 2 to 4 d postflight. A follow-up analysis showed that the foot pitch, ankle dorsiflexion and pelvis roll angles were significant predictors of changes in toe clearance.

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Based on analysis of toe clearance, author found that crewmembers returning from long-duration spaceflight may have an increased risk of tripping only on landing day compared to preflight - with subjects exhibiting either an increased variability (as measured by IQR) or decreased median. Median toe clearance and IQR at all time points after landing day were not significantly different from their preflight values during recovery, indicating that they regained some locomotor control, despite experiencing the acute effects of readapting to Earth’s gravity. A secondary analysis revealed that changes in foot and ankle flexion angles and pelvis roll angle were significant predictors for changes in toe clearance, thus showing that the crewmembers tried to reestablish their " known " walking pattern, instead of developing a new, untested motor control strategy.

Dynamic Visual Acuity During Walking After Long-Duration Spaceflight Astronauts experience alterations in gaze control as a result of adaptive changes in eye-head coordination produced by microgravity exposure. This may lead to potential changes in postflight visual acuity during head and body motion.Gaze control orchestrated by the CNS is critical to dynamic visual acuity (DVA). The gaze stabilization system coordinates movement of the eyes and head so that a stable retinal image is maintained during head and body motion. An important component of this control system is the vestibulo-ocular reflex (VOR).

VOR response properties are modifi ed during and after spaceflight, but the degree of adaptation varies among subjects and experimental conditions.

These data suggest that, initially on orbit and following the return to Earth, the VOR is continually in adaptive flux, searching for a new dynamic equilibrium. Under these conditions, the VOR maintains plasticity and, given sufficient time, adaptively modifies to re-establish stable vision during head perturbations.

Gaze is the direction of the visual axis with respect to space. It is defined as the sum of eye position with respect to the head and head position with respect to space. Coordinated eye-head movements toward an offset visual target usually consist of a combined saccadic eye and VOR response that shifts gaze onto a target.

It has been previously demonstrated that exposure to the microgravity of spaceflight induces modification in eye-head coordination during target acquisition. Target acquisition tasks requiring coordination of eye and head movements have shown degraded performance and the presence of corrective saccades, particularly for targets placed outside the central field-of-view and located in the vertical plane requiring a pitch head movement for target acquisition. Changes in these parameters after spaceflight contributed to a near doubling of the latency required to fixate peripheral targets.

During the adaptation to space, primates trained to perform a visual target acquisition task that required accurate perception of the peripheral targets showed delays in the onset of the gaze response and made significantly more errors in identifying the visual characteristics of peripheral targets.

Deficient gaze control during periods of adaptive change, such as the fi rst days of microgravity exposure or re-exposure to a gravitational environment, could cause oscillopsia (illusory movement of the visual world), blurred vision, and decrements in DVA. In such cases, stationary objects may appear to bounce up and down or move back and forth during head movements.

Visual disturbances like these could adversely affect the performance of critical mission tasks: the successful completion of extravehicular construction activities requiring precise eye-hand coordination could be jeopardized; it may become diffi cult to read instruments or locate switches on control panels; and the ability to rapidly egress a vehicle in an emergency could be compromised. Simply stated, mission success and crew safety depend on a crewmember’s ability to see well.Earlier work showed that DVA is reduced following longduration spaceflight.

There were 14 crewmembers (astronauts/cosmonauts) taking part in long-duration missions at the International Space Station of an average ( ± 95% confidence interval) duration of 185 ( ± 7.2) d who volunteered to participate in this study. Of the 14 subjects, 7 had prior long-duration( ≈ 6 mo) spaceflight experience. There

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity were 13 men and 1 woman, and their ages ranged from 37 to 55 (mean = 46) yr. All gave informed consent according to the requirements of the Committee for the Protection of Human Subjects at NASA Johnson Space Center.

To evaluate the effect of spaceflight on DVA, data were collected both pre- and postflight. The preflight testing schedule consisted of three separate visits during the months preceding launch. A baseline for each subject was determined from data collected during the final two of these three visits. Nominally, the postflight schedule consisted of five test sessions that were conducted on landing day and on days 1, 2, 3/4, and 6/7 after landing, according to crewmember availability. Only 3 of the 14 subjects were available for testing on landing day; only 1 of those was able to complete the treadmill-walking protocol ( ≈ 4 h after landing).

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Results Fig. 1 shows dynamic visual acuity data from 14 crewmembers after their return from long-duration ( ≈ 6 mo) stays in space. These data show a decrement in postflight walking acuity. With the timescale fixed relative to landing, the population mean shows a consistent improvement in DVA performance during the postflight recovery period.

In the figure, data are normalized to the subjects’ preflight DVA values, which are represented on the y-axis at 0. The error bars in the figure represent the 95% confidence interval of the mean for each test day. Therefore, postflight test days on which error bars do not intersect the y-axis at 0 indicate days that DVA performance significantly differed from preflight values.

Recovery curves for individual subjects did not necessarily follow a pattern of continuous improvement with each passing day. Authors observed that subjects recovered and readapted at different rates, introducing noticeable variation in the group’s recovery curves, particularly on postflight day 2.

On this day, some subjects appeared to improve while others showed a decrement. To better understand this disparity, which we believed could be attributed to individual differences in adaptation rates, the data for the seven subjects with previous long-duration spaceflight experience were replotted after imposing an artificial 1-d " delay " in their recoveries. This temporal shift reduced the response variability and revealed a change in the morphology of the group recovery curve to one that 1) produced a greater decrement in postflight day 1 performance, and 2) showed an unexpected DVA reduction in the group’s recovery curve at day 3/4 ( Fig. 2 ).

Postflight changes in gaze control produced decreases in DVA during walking for 14 subjects following long duration exposure to microgravity. Each successive eye chart line represents an increase in optoytpe size of

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity roughly 25%. Therefore, the subject that showed a 2.5 line change would require that font sizes be increased by over 60% in order to see with equal clarity during the given walking conditions. The population mean showed a consistent improvement in DVA performance during the week-long postflight recovery period, although the individual recovery rates varied.

When data for the seven subjects with previous long duration spaceflight experience were shifted by a day( Fig. 2 ), group recovery curves aligned in a manner that suggests these subjects were 1 d ahead of the others in their recoveries. The unexpected DVA reduction that appears in the groupâ&#x20AC;&#x2122;s recovery curves on day 3/4 is similar to one observed following prism adaptation in which the after effect showed two separate time courses of decay and increase. Hatada et al. suggested that this behavior could be caused by two separate underlying neural mechanisms with different time scales. In this application, it suggests a more complex readaptation process than simply a gradual return to " normal " following spaceflight.

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The data show changes in the ability of crewmembers to clearly see visual targets while walking after spaceflight, but authors believe these results may significantly underestimate the decrements in visual performance that are actually experienced during and immediately following landing.

One study limitation was that, with the exception of one subject, all of our DVA data were collected no earlier than 24 h after the landing. Given how rapidly gaze control re-adapts, authors suspect that the decrement in visual acuity at the actual time of landing was likely much higher than what we measured at our first postflight data collection sessions. Ideally, returning crewmembers would be tested immediately upon landing, but their schedules during those critical postflight hours precluded this. The test paradigm also presented a bestcase scenario for successful optotype recognition because optotypes were displayed for 500 ms, enough time to encompass a full step cycle, including periods when head velocity would have been zero. Stride cycle timing has been shown to influence target acquisition success, so authors suspect it also plays a role in acuity.

The test could be made more sensitive by restricting the optotype display duration to periods when head velocity is higher, for example, during heel-strike events. A third consideration is that walking is an active, well practiced activity and feed-forward control mechanisms facilitate it by producing compensatory eye movements.

Therefore, a walking DVA test probably underestimates the amount of decrement in visual performance that would be expected during passive, unpredictable motion, such as would occur during a landing when crewmembers are strapped into a moving vehicle.

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D ID YOU KNOW ?

G ENDER D IFFERENCES IN B EDREST:AUTONOMIC AND N EUROENDOCRINE C HANGES AND VASCULAR R ESPONSES IN L OWER AND U PPER E XTREMITIES

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Female astronauts are more susceptible to orthostatic hypotension and presyncope after space flight than are male astronauts. However, most space flight and bed rest studies that have sought to understand the mechanisms contributing to this increased incidence of orthostatic hypotension have not included women. Consequently, many conclusions about the effects of microgravity or simulated microgravity on humans are seriously flawed in that they fail to describe mechanisms in the very people who have the most serious problems.

Before flight, low vascular resistance in female astronauts is not associated with lower sympathetic responsiveness, as their supine and standing norepinephrine levels are similar to those of men. This suggests that the gender differences may lie in the responsiveness of the vasculature itself. Premenopausal women appear to have greater endothelium-dependent venodilatory as well as vasodilatory responses than those of men. This suggests that their lower resistance and lower venous return may be nitric oxide-mediated.

Many studies have documented hemodynamic changes that occur during and after space flight or bed rest; very few have examined directly vascular responses, fewer still have compared vascular responses in men versus women before and after bed rest, and none has examined both arteries and veins. Therefore, the first purpose of this study was to examine vascular responsiveness in arteries and veins, in women versus men, before and after bed rest.

Thirty-one subjects participated in 60 or 90 day 6 degree head-down bed rest (not all subjects completed all days due to two hurricane evacuations and others left early for personal reasons) conducted at the General Clinical Research Center (GCRC) Satellite Flight Analogs Research Unit at the University of Texas Medical Branch in Galveston, Texas (UTMB). All protocols were reviewed and approved by the NASA Johnson Space Center Committee for the Protection of Human Subjects, UTMB Institutional Review Board and UTMB GCRC Advisory Committee. Informed consent forms were signed prior to participation in the study.

Subjects were healthy, normotensive, non-smokers, not obese, taking no medications, and had passed a psychological examination. Female subjects were premenopausal, with regular menses lasting 28 Âą 2 days and were studied across the menstrual cycle, starting at menses. Because hormonal changes affect the cardiovascular responses in women, the bed rest study was arranged so that all measurements were taken at the same time in the menstrual cycle (during menses).

The dorsal hand and foot vein and phenylephrine/sodium nitroprusside protocols were performed once during the pre-bedrest period after approximately 8-12 days of diet stabilization, and around bed rest days 30, 60 and 90 days, if applicable. These three protocols were performed on consecutive days. Female subjects were admitted to bed rest such that these test days would fall at the beginning of menstrual cycle. The reactive hyperemia and sublingual nitroglycerin protocols were performed once during pre-bedrest after 6-8 days of diet stabilization, and around bed rest days 7, 21, 31, 49, 60, 75, and during the postbed rest period on day 0 and 3.

Results: Dorsal vein size in response to bed rest baseline foot vein size was significantly smaller in women compared to men prebed rest. By day 60 however, there were no differences in foot vein size such that vein size decreased in the men and women over the course of bed rest. Baseline hand vein size was similar between men and women prebed rest and did not change in response to bed rest.

The absolute change in artery diameter from resting to peak diameter following sublingual nitroglycerin administration was greater in the arm than in the leg, changed across bed rest days, and the change across bed rest days was different between the arm and the leg. Similar to previous findings, there was no effect of gender.

Parasympathetic modulation and baroreflex sensitivity decreased with bed rest, with women experiencing a larger decrease in baroreflex sensitivity by day 30 than men. The sympathetic activation of men and parasympathetic responsiveness of women in blood pressure control during physiological stress were preserved throughout bed rest. During PE infusions, women experienced saturation of the R-R interval at high frequency, whereas men did not, revealing a sex difference in the parabolic relationship between high-frequency R-R interval, a measurement of respiratory sinus arrhythmia, and R-R interval. These sex differences in blood pressure control during simulated microgravity reveal the need to study sex differences in long duration space flight to ensure the health and safety of the entire astronaut corps.

Reference:

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Arzeno NM, Stenger MB, Lee SMC, Ploutz-Snyder R, and Platts SH. Gender differences in blood pressure control during 6 degree headdown tilt bed rest. American Journal of Physiology: Heart Circulatory Physiology.

2013. April; 304(8):H1114-23.

Risk of Orthostatic Intolerance During Re-Exposure to Gravity

Metabolic Consequences of Garments Worn to Protect Against Post-Spaceflight Orthostatic Intolerance Astronauts returning from spaceflight experience orthostatic intolerance, which may result in orthostatic hypotension and presyncope. To protect against potential adverse effects of orthostatic intolerance, astronauts have worn an antigravity suit (AGS) during Space Shuttle re-entry and landing. The AGS compresses the abdomen and legs so that venous return is enhanced and blood pressure (BP) is maintained after spaceflight.

Although the AGS protects against orthostatic intolerance , AGS inflation increases the metabolic rate while walking and may prevent successful completion of an unaided emergency egress from a space vehicle.

The purpose of this study was to compare the metabolic cost of walking while wearing the AGS, while wearing thigh-high elastic compression garments, and while wearing normal exercise clothes.

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Using a modified Air Force Class III Physical Examination administered by the NASA JSC Human Test Subject Facility, 10 volunteers (5 men, 5 women; 36 ± 8 yr,172 ± 10 cm, 73 ± 16 kg, mean ± SD) were cleared for participation. Before participating in the study, subjects received verbal and written explanation of the test procedures and provided written informed consent. Test protocols were approved by the NASA JSC Committee for the Protection of Human Subjects.

The AGS (David Clark Company, Worcester, MA) consists of five interconnected air bladders that cover the abdomen, thighs, and calves. The subject’s height and weight were used to determine the appropriate AGS size using the standard sizing chart provided by the NASA JSC Space Suit and Crew Survival Systems Branch. Sizing was confirmed by ensuring that the knee joint was properly aligned with the provided opening and that the bottom of the AGS did not extend beyond the ankle. NASA Flight Rules state that for flights greater than 11 d, the AGS must be inflated to at least 1.0 psi (52 mmHg) during re-entry (Space Shuttle Operations Flight Rules, NSTS-12,820; Volume A, Section 13-Aeromedical; 2002). Because many crewmembers routinely inflate their AGS to 1.5 psi(78 mmHg), testing for this study was conducted with the AGS inflated to 1.5 psi.

The elastic compression garments (JOBST r Relief Medical LegWear, BSN Medical, Inc., Charlotte, NC) covered the thighs and calves and were similar to those recently evaluated postflight in a small set of Space Shuttle astronauts. Garments covering only the legs were evaluated because astronauts frequently report discomfort caused by AGS inflation over the lower abdomen, particularly after performing the fluid-loading protocol. Elastic compression garment size was determined according to the manufacturer’s recommendations based on the circumference of the ankle and of the largest part of the calf and thigh while the subject was supine with the knees slightly bent. The elastic compression garments provided graded compression from the ankle to the thigh, with 0.6-0.8 psi (30-40 mmHg) of pressure at the ankle and approximately 0.12 psi (6 mmHg) at the top of the thigh.

Results Standing HR was significantly different between conditions [F(2,18) = 5.61, P = 0.013] ( Table I ). Standing HR while wearing the AGS was 16 ± 7% lower ( P = 0.02, d = 0.78) than when wearing elastic compression garments and 10 ± 4% lower ( P = 0.04, d = 0.72) than while unsuited. Standing HR while wearing elastic compression garments was not signifi cantly different from standing HR in the unsuited condition. Standing systolic BP was not affected by condition [F(2,18) = 2.03, P = 0.16], but there was a tendency for an effect of condition on diastolic BP [F(2,18) = 3.45, P = 0.054].

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity Vo2 (L.min −1 ) during walking was significantly different across conditions [F(2,18)= 12.73,P < 0.001](Fig. 1).Vo2 was significantly greater when subjects walked in the AGS than when wearing the elastic garments (12 ± 2%, P = 0.002, d = 0.75) or were unsuited (15 ± 4%, P < 0.001, d = 0.82). Similar results were obtained when Vo2 was expressed relative to body mass (ml.kg−1 z min−1 ). Thus, the caloric cost of walking was significantly different across conditions [F(2,18) = 15.41, P < 0.001]. The caloric cost of walking in the AGS (29 ± 2 kcal) was greater than in the elastic garment (26 ± 1 kcal, P = 0.001, d = 0.70) and the unsuited conditions (25 ± 1 kcal, P < 0.001, d = 0.82). Vo2 also was significantly different between the three conditions [F(2,18)=21.58, P < 0.001]. Vo2 was greater when walking in the AGS than when wearing elastic compression garments (11 ± 2%, P < 0.001, d = 0.91) or when unsuited (16 ± 3%, P < 0.001, d = 1.08).

Additionally, VE during walking was different between conditions [F(2,18) = 14.24, P <0.001]. VE was greater when walking in the AGS than when wearing elastic compression garments (9 ± 2%, P = 0.002, d = 0.57) or when unsuited (13 ± 3%, P < 0.001, d = 0.77). There were no differences between the elastic compression garment and unsuited conditions in the metabolic variables while walking.

HR during walking was significantly different between the conditions [F(2,18) = 18.36, P < 0.001]. While wearing the AGS HR was 9 ± 2% higher ( P < 0.001,d = 0.75) than while wearing elastic compression garments and 8 ± 2% higher ( P < 0.001, d = 0.63) than when unsuited ( Table I ). Systolic BP during walking also was different across conditions [F(2,18) = 7.28, P = 0.005]. Systolic BP tended to be greater (4 ± 2%, P = 0.07, d = 0.46) while wearing the AGS than while wearing elastic compression garments and was greater than when unsuited (7 ± 2%, P = 0.04, d = 0.72). Diastolic BP was significantly different between the conditions [F(2,18) = 3.71, P = 0.045], but post hoc analyses did not reveal any specific between condition differences.

No differences between the elastic compression garment and unsuited conditions occurred in these cardiovascular variables while subjects were walking. RPE [F(2,18) = 16.55, P < 0.001] and level of discomfort

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity [F(2,18) = 56.31, P < 0.001] during walking were significantly different across conditions. RPE and the level of discomfort were higher ( P < 0.001) while in the AGS than while wearing elastic compression garments and in the unsuited condition ( Fig. 2 ), but there were no differences between the elastic compression garment and unsuited conditions.

The primary finding of this study is that the metabolic cost of walking while wearing elastic compression garments was no greater than when wearing normal exercise clothes and was significantly less than when wearing the AGS. Similar effects were observed with regard to the perceptions of effort and discomfort. This information is relevant to astronauts who routinely wear compression garments designed to protect against spaceflightinduced orthostatic intolerance during and after vehicle landing.

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Previous work from our laboratory has demonstrated that the AGS is an effective countermeasure to orthostatic intolerance following actual spaceflight and during hypovolemia, a laboratory model of spaceflight adaptations.

However,use of the AGS has side effects that do not present themselves until an astronaut is required to walk or run to complete an unaided egress from the Space Shuttle or other space vehicle. It is important to identify or develop a garment that protects against spaceflight induced orthostatic intolerance and reduces or eliminates factors that might impair an astronaut’s successful completion of post-landing critical tasks.

Protection against orthostatic intolerance is important for astronauts returning from spacefl ight, particularly in situations during which ground support is not immediately available, such as an emergency landing or a ballistic re-entry of the Soyuz. Although an inflated AGS provides protection against orthostatic intolerance, it is bulky, can be uncomfortable to wear for extended periods, and impairs walking and running. Before the retirement of the Space Shuttle, in the event of an emergency egress, astronauts were expected to exit the Shuttle wearing the ACES and move quickly to a distance of 380 m (1246 ft).

In this scenario, the helmet visor had to be closed to protect against toxic gas inhalation and astronauts were to receive 100% oxygen from a pressurized gas bottle attached to the suit harness. However, expired respiratory gases mix with the supplied oxygen and are not completely expelled. Thus CO2 accumulates in the ACES non-conformal helmet. Factors that increase metabolic rate, such as working against the AGS and its bulk, also increase Vco2 , thus elevating CO2 levels in the helmet; elevated inspired CO2 would impair the ability to perform physically and mentally. Although the emergency egress scenarios for the next generation of space vehicles have not been fully defined, authors expect that an inflated AGS would similarly impair an astronaut’s ability to egress the vehicle and to assist other crewmembers.

In the event that an antiorthostatic intolerance garment is required to be worn in a partial gravity environment after prolonged microgravity exposure, such as a 6-mo mission to Mars, we would expect that an elastic compression garment would have three important benefits specific to these exploration missions.

First, elastic compression garments have a smaller mass and volume requirement for stowage on the vehicle than an AGS style garment and would have no requirement for supporting hardware components that would need maintenance in preparation for their use. There would be no air bladders to check for leakage, no pressurized gas source to preserve, and no pressure regulators to maintain. Additionally, there would not be a requirement for a suit-vehicle interface to design or maintain.

Second, the lower metabolic cost associated with wearing elastic garments reduces the consumption of important resources (such as breathing air, water, and CO2 scrubbers) in the habitat and the EVA suit.

Third, elastic compression garments are routinely used to prevent orthostatic hypotension in clinical populations and considerable experience exists in developing a garment that can be worn comfortably for extended durations. The elastic garments could be worn under normal clothing and in the EVA suit during the mission, and also would have utility during readaptation to normal gravity on return to Earth.

Three other benefits also may be realized by wearing elastic compression garments rather than the AGS during egress and ambulation. First, the elastic compression garments are not bulky like the inflated AGS and, therefore, should not inhibit ambulation by themselves or through interactions with the ACES or an EVA suit. The treadmill speed used for this study was based on our previous work in which we determined that 5.6 km.h−1 was the fastest speed at which astronauts could be reasonably expected to ambulate in the ACES with the AGS inflated . Several subjects attempted to complete an unaided egress simulation at different treadmill speeds and subjects either fatigued very quickly or were unsteady at speeds greater than 5.6 km.h−1 . A less bulky compression garment used with the ACES or EVA suit may allow an astronaut to move away from the vehicle at a faster rate or with lower rates of CO2 accumulation while decreasing the likelihood of falling. Falling may be

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity a specific concern during extraterrestrial EVA as astronauts adapt to working in a partial gravity environment while controlling a center of gravity altered by wearing the EVA suit.

Second, the elastic compression garments would need no adjustment to prevent them from interfering with walking or egress from a space vehicle. To decrease the effort of egress while wearing the AGS with the ACES, some astronauts suggested to us that they would simply deflate the AGS after landing. Although this might increase the likelihood of a successful egress, astronauts would receive less protection against orthostatic intolerance if they had to stop to rest or aid a crewmate.

Moreover, authors have observed that the AGS pressure decreases over time, particularly with bending at the hips and knees; the AGS is rated to leak at a constant rate of 100 ml. minâ&#x2C6;&#x2019;1 when the astronaut is not moving.

The pressure drop may be greater during ambulation when the internal pressure of the AGS is elevated above the relief-valve pressure. In a subset of the current subjects we measured AGS pressure before and after walking and observed that AGS pressure decreased approximately 0.5 psi during the 5-min walk.

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Unfortunately, after disconnecting from the space vehicle the AGS cannot be reinfl ated without a pressurized gas source and, therefore, the level of protection previously supplied by the fully infl ated AGS cannot be recovered. Elastic compression garments, if proven to successfully protect against orthostatic intolerance after spaceflight, could be worn during egress without concerns for adjusting them for egress from the vehicle and without decreased efficacy with ambulation.

Third, authors expect that the lower metabolic cost of walking and working in the elastic compression garments compared to the AGS would result in less heat production and body heat storage. This is particularly important in astronauts who have a decreased thermoregulatory capacity after spaceflight and who, therefore, may have a greater propensity for heat injury. To prevent overheating while wearing the ACES and potentially exacerbating decreased orthostatic tolerance and exercise capacity, a liquid cooling garment, consisting of close-fitting shirt and pants worn under the ACES, was added to the ensemble in 1994. Heat is removed from the surface of the skin and from the interior of the ACES by circulating chilled water through a network of smalldiameter vinyl tubing sewn into the fabric of the liquid cooling garment. However, despite the use of a liquid cooling garment, core temperature was significantly elevated in four crewmembers during a nominal Space Shuttle re-entry and landing (STS-90, April 1998).

This occurred before the astronauts exited the Space Shuttle; authors expect that the cooling capacity of the liquid cooling garment would be quickly exceeded with the addition of physical work associated with vehicle egress. Furthermore, in the current ACES design the liquid cooling garment is not functional on vehicle egress since the water is circulated and cooled thermoelectrically using Shuttle power. Future space suits worn during reentry and landing may have similar limitations.

Temazepam, but Not Zolpidem, Causes Orthostatic Hypotension in Astronauts After Spaceflight Insomnia is a common symptom, not only in the adult population but also in many astronauts.Four percent of the American population uses sedative hypnotics for sleep in any given year. Sleeping medications, such as benzodiazepines and imidazopyridines, are the most common drugs prescribed for acute insomnia. Benzodiazepines used clinically have not been shown to decrease arterial pressure, except in the elderly. The mechanism of this effect in older patients has not been elucidated. Another population, American astronauts, also uses sedative hypnotics due to their severe problems with insomnia during spaceflight.

In fact,14% of astronauts use sedative hypnotics, most commonly temazepam, during their missions. After landing, about 20% of returning astronauts suffer from symptomatic orthostatic hypotension. Every effort has been made to determine the mechanisms of this problem since it endangers the crew and the vehicle. It is known that hypovolemia and autonomic dysfunction both contribute to postflight orthostatic hypotension.

This study was conducted in two parts. The first part was a prospective study in laboratory volunteers (groundbased subjects) on the effects of temazepam on cardiovascular responses to standing. In addition, a retrospective analysis was performed on astronautsâ&#x20AC;&#x2122; preflight and postflight stand tests with and without the influence of temazepam or zolpidem. The National Aeronautics and Space Administration Johnson Space Center Committee for the Protection of Human Subjects approved these protocols.

Results The anthropometric data for all subjects are presented in Table 1. Age, body weight, and height did not differ significantly among any of the groups. Between January 1990 and December 1996, 13.7% of astronauts took temazepam and 4.6% took zolpidem during flight. Therefore, astronauts took temazepam three times more

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than zolpidem during this period.

Ground-based results In ground-based subjects, one subject who had not become presyncopal before taking temazepam became presyncopal during standing after taking it. Two additional subjects reported feeling lightheaded and dizzy the morning after taking temazepam but before reporting to the laboratory. These two subjects did not become presyncopal during their stand tests. Figure 1 shows that finger arterial pressures and heart rates decreased in the subject who became presyncopal after taking temazepam. Before temazepam (upper panel), systolic pressure was maintained the entire time of standing. After temazepam, systolic pressure dropped to 70 mm Hg

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(bottom panel), and the subject became presyncopal. Standing heart rate after temazepam was 15 beats per minute higher than before temazepam until presyncope occurred.

Figure 2 represents supine and standing arterial pressures and heart rates before and after 30 mg temazepam in the ground-based subjects. As a group, there was no effect of temazepam on supine or standing arterial pressures. Supine heart rates were not different after temazepam, but standing heart rates were significantly higher (p < 0.05).

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Carotid baroreceptor reflex test Carotid baroreceptor-cardiac reflex responses before and after temazepam are shown in Figure 3 and Table 2. Temazepam resulted in no change in slope, range, or operational point.

Flight-based Results Figure 4 depicts supine and standing systolic and diastolic pressures and heart rates for the subjects who took temazepam the night before landing and those who did not. No astronaut took any drug before flight. Before flight (Fig. 4, left), supine and standing pressures and heart rates were not different between groups, although pressures were somewhat lower in the temazepam group.On landing day (Fig. 4, right), supine pressures were higher than before flight in both groups, but those who had taken temazepam had very dramatic decreases in systolic pressure with standing that were significantly greater than in those who had not taken the drug (p <0.05). There were no intergroup differences in supine or standing heart rates before flight; however, on landing day, the temazepam group had significantly higher standing heart rates than those who did not take the drug.

Figure 5 depicts supine and standing systolic and diastolic pressures and heart rates before flight and after flight in the control group of astronauts versus those who took zolpidem the night before landing. Unlike the temazepam data, there were no intergroup differences in supine or standing values either before flight or after flight.

This study was initially undertaken because 14% of astronauts were taking in-flight sleeping medications, and it was unknown what effects this practice had on arterial pressure control during and after flight. There is a significant finding from this study. In returning astronauts, but not in age-matched ground-based subjects, the use of temazepam is clearly associated with orthostatic hypotension. Even so, temazepam did cause presyncope in one ground-based subject. The astronauts and the ground-based subjects differ primarily in that the astronauts have been hemodynamically compromised by spaceflight.

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This finding in this unique population could also help to explain why a similar side effect is seen in elderly patients , who are also compromised, but is not seen in younger patients. This finding was not repeated in astronauts who used zolpidem. These results suggest that the use of temazepam as an in-flight sleeping aid has contributed significantly to the high incidence of postspaceflight orthostatic hypotension in returning astronauts. More importantly, clinicians who prescribe temazepam as a sleeping aid should be aware that it can be associated with orthostatic hypotension, particularly in deconditioned patients.

These points will be discussed in the following paragraphs.In the astronaut subjects, temazepam caused significant decreases in standing systolic pressure after spaceflight (Fig. 4). In fact, their hemodynamic responses to upright posture fell within the range of clinical orthostatic hypotension: systolic pressure decreases greater than 20 mm Hg and/or heart rate increases greater than 27 beats per minute.

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Risk of Orthostatic Intolerance During Re-Exposure to Gravity

Zolpidem had no such effects. There are several reasons that temazepam and zolpidem had different effects.

First is the difference in half-lives. The halflife of temazepam is 11-20 h, and the halflife of zolpidem is 1.5-4 h. Therefore, zolpidem is probably eliminated by the time of landing.

Second, there are differences in the mechanisms of actions between the two drugs. Temazepam, a benzodiazepine, binds nonselectively to all three subtypes of the benzodiazepine receptor (BZ1, BZ2, and BZ3).

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Thus, in addition to BZ1 sedative effects, temazepam also has BZ2, and BZ3â&#x20AC;&#x2122;s anticonvulsant, myorelaxant, and anxiolytic effects. The muscle relaxant properties probably enhance venous pooling during upright posture.

This normally does not result in systolic pressure decreases because baroreflex-mediated increases in heart rate maintain cardiac output. This idea is supported by the current study.

In ground-based subjects, carotid baroreceptor- cardiac reflex responses were intact after temazepam, suggesting that the drug does not affect autonomic control of arterial pressure. This finding matches clinical studies in young people.

However, in individuals who are hemodynamically compromised, such as the elderly, temazepam can cause significant decreases in systolic pressure. Authors suggest that returning astronauts are more affected by temazepam than groundbased subjects because, like the elderly, they are already hemodynamically compromised. They have reduced plasma volume , sympathetic dysfunction, increased leg compliance, and skeletal muscle atrophy.

Unlike temazepam, zolpidem had no effect on arterial pressure and heart rate responses to standing after spaceflight. Zolpidem is not a benzodiazepine, but an imidazopyridine, which only selectively binds the BZ1 benzodiazepine receptor subtype. Thus, it does not have BZ2 and BZ3 myorelaxant properties and is not likely to aggravate venous pooling. Zolpidem rarely causes cardiovascular effects such as hypotension or tachycardia , even in elderly patients.

Ground-based subjects in this study did not, as a group, experience low blood pressure during standing after temazepam, but they did have significantly higher standing heart rates. These findings were not unexpected.

Several studies have shown that temazepam does not affect arterial pressure but can cause significant increases in heart rate during sitting, standing, and lowerbody negative pressure.

However, one subject in the study did become presyncopal after taking temazepam, and two additional subjects reported feeling dizzy and lightheaded after taking the drug. In the retrospective analysis of the astronaut data, authors were limited by the fact that the only hemodynamic measurements available were heart rate and arterial pressure.

A more complete study would have stroke volume, cardiac output, and peripheral resistance, among other measurements. Thus, we cannot definitively determine the mechanisms of the hypotension in the temazepam group. However, that does not lessen the importance of these observations.

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D ID YOU KNOW ?

P NEUMATIC ANTISHOCK GARMENTS (PASG)

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Pneumatic antishock garments (PASG) are used to stabilize and increase blood pressure in hypovolaemic patients. The basic design of PASG has remained fundamentally unchanged since its description by Crile (1905), and similar garments have found widespread use in high-performance aircraft to counter accelerationinduced venous pooling associated with combat manoeuvres.

Hemorrhage from pelvic blood vessels after trauma or obstetric delivery are major health care problems. Trauma is a leading cause of death worldwide and a major cause of lost quality-adjusted life years (QALYs). Treatment of pelvic trauma is difficult since hemorrhage can be massive and it is difficult to apply direct pressure to the bleeding vessels. Postpartum hemorrhage is the leading cause of obstetric deaths and causes an estimated 150,000 maternal deaths per year. Definitive control of severe pelvic bleeding from any cause often requires aggressive measures such as arterial embolization, laparotomy, internal fixation, or pelvic packing. These procedures are difficult to perform because they require immediate access to sophisticated medical and surgical expertise and equipment. Severe hemorrhage is often aggravated by disseminated intravascular coagulation. Blood volume must be maintained by transfusion of red blood cells, platelets, and clotting factors. Transfusion requirements can be massive and overwhelm the capacity of even large facilities. These issues are particularly difficult in low resource environments.

Ideally pelvic hemorrhage could be controlled by simple external pressure. This could provide time to mobilize more sophisticated resources and might decrease transfusion requirements and the need for aggressive therapy. Pneumatic anti-shock garments (PASG), also called medical or military anti-shock trousers (MAST), have been shown to greatly decrease pelvic blood flow, and case reports imply that they are effective in patients with pelvic injuries and postpartum hemorrhage. PASG have little or no benefit in treating trauma patients in general. However, most of the patients enrolled in clinical trials had thoracic or abdominal trauma and had ready access to definitive surgery. In addition PASG have little effect on the general circulation. They only autotransfuse about 250 cc of blood from the lower body into the central circulation and have little or no effect on cardiac output. These findings would explain differing outcomes for upper body versus pelvic hemorrhage.

In their favor PASG have been used thousands of times and have proven quite safe. Unfortunately PASG are complicated, expensive, and rarely available in the low resource areas where they would seem most useful. A simple and less expensive alternative to PASG was developed by The National Aeronautics and Space Administration (NASA). This non-pneumatic anti-shock garment (NASG) is made of neoprene and is tightly applied to the patient using Velcro straps. It has been commercialized as the ZOEX Non-Inflatable Anti-Shock Garment (ZOEX, Ashland, OR, USA). The NASG has been shown to decrease postpartum blood loss by 50% and improve survival rates from postpartum hemorrhage. Although the NASG is less expensive than commercial PASGs it currently has limited availability.

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Garvin NM, Levine BD, Raven PB, Pawelczyk JA. Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression. Exp Physiol. 2014 Jan;99(1):101-10.

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Ad Astra ! To The Stars! In Peace For All Mankind !

Mr. Rick R. Dobson, Jr. (Veteran U.S Navy)

International Space Agency(ISA) ( Non足Profit Organization ) P.O. Box 541053 Omaha, Nebraska 68154 United States