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NASA NTRS1990

Neuronal plasticity in relation to long-duration spaceflight

Exposure to microgravity leads to a marked reduction in sensory-motor stimuli to the vestibular, proprioceptive and somatosensory systems. Long-duration missions, such as those proposed for a trip to Mars, may lead to significant changes in neural function. This paper presents results based on studies of sensory deafferentation of specific brain regions and detailed changes which occur in neuronal architecture. Data from these studies emphasize the need for further research related to sensory system deprivation and the development of new unique countermeasures for long-duration space flight.

Hillman, Dean E.↗
NASA NTRS2015

Astronaut Preflight Cardiovascular Variables Associated with Vascular Compliance are Highly Correlated with Post-Flight Eye Outcome Measures in the Visual Impairment Intracranial Pressure (VIIP) Syndrome Following Long Duration Spaceflight

The detection of the first VIIP case occurred in 2005, and adequate eye outcome measures were available for 31 (67.4%) of the 46 long duration US crewmembers who had flown on the ISS since its first crewed mission in 2000. Therefore, this analysis is limited to a subgroup (22 males and 9 females). A "cardiovascular profile" for each astronaut was compiled by examining twelve individual parameters; eleven of these were preflight variables: systolic blood pressure, pulse pressure, body mass index, percentage body fat, LDL, HDL, triglycerides, use of anti‐lipid medication, fasting serum glucose, and maximal oxygen uptake in ml/kg. Each of these variables was averaged across three preflight annual physical exams. Astronaut age prior to the long duration mission, and inflight salt intake was also included in the analysis. The group of cardiovascular variables for each crew member was compared with seven VIIP eye outcome variables collected during the immediate post‐flight period: anterior-posterior axial length of the globe measured by ultrasound and optical biometry; optic nerve sheath diameter, optic nerve diameter, and optic nerve to sheath ratio‐ each measured by ultrasound and magnetic resonance imaging (MRI), intraocular pressure (IOP), change in manifest refraction, mean retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT), and RNFL of the inferior and superior retinal quadrants. Since most of the VIIP eye outcome measures were added sequentially beginning in 2005, as knowledge of the syndrome improved, data were unavailable for 22.0% of the outcome measurements. To address the missing data, we employed multivariate multiple imputation techniques with predictive mean matching methods to accumulate 200 separate imputed datasets for analysis. We were able to impute data for the 22.0% of missing VIIP eye outcomes. We then applied Rubin's rules for collapsing the statistical results across our 200 multiply imputed data sets to assess the canonical correlation between the eye outcomes and the twelve astronaut cardiovascular variables available for all 31 subjects. Results: A highly significant canonical correlation was observed among the canonical solutions (p<.00001), with an average best canonical correlation of.97. The results suggest a strong association between astronauts' measures of cardiovascular health and the seven eye outcomes of the VIIP syndrome used in this analysis. Furthermore, the "joint test" revealed a significant difference in cardiovascular profile between male and female astronauts (Prob > F = 0.00001). Overall, female astronauts demonstrated a significantly healthier cardiovascular status. Individually, the female astronauts had significantly healthier profiles on seven of twelve cardiovascular variables than the men (p values ranging from <0.0001 to <0.05). Male astronauts did not demonstrate significantly healthier values on any of the twelve cardiovascular variables measured

Otto, Christian↗
NASA NTRS2002

Comparison of echocardiographic changes after short- and long-duration spaceflight

BACKGROUND: Previous echocardiographic studies of astronauts before and after short-duration (4-17 d) missions have demonstrated a decrease in resting left ventricular stroke volume, but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long-duration (129-144 d) spaceflight have been rare and their overall results equivocal. METHODS: Echocardiographic measurements (M-mode, 2-D, and Doppler) were obtained from short-duration (n = 13) and long-duration (n = 4) crewmembers to evaluate cardiac chamber sizes and function. RESULTS: Compared with short-duration astronauts, long-duration crewmembers had decreases in EF (+6+/-0.02 vs. -10.5+/-0.03%, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07%, p = 0.015), and an increase in left ventricular end systolic volume (-12+/-0.06 vs. +39+/-0.24%, p = 0.011). CONCLUSIONS: These data suggest a reduction in cardiac function that relates to mission duration. As the changes in BP and circulating blood volume are reported to be similar after short- and long-duration flights, the smaller EF after longer spaceflights may be due to a decrease in cardiac function rather than altered blood volume.

short duration↗
NASA NTRS2000

Comparison of Echocardiographic Measurements Before and After Short and Long Duration Spaceflight

Previous echocardiography studies in astronauts before and after short duration (4 - 17 days) missions have demonstrated a decrease in resting left ventricular (LV) stroke volume (SV), but maintained ejection fraction (EF) and cardiac output. Similar studies before and after long duration (129 - 144 days) spaceflight have been rare and their overall results equivocal. The purpose of this work was to compare the echocardiographic measurements (M-mode, 2-D and Doppler) from short duration (n = 13) and long duration (n = 4) crewmembers. Compared to short duration astronauts, long duration crewmembers had a significantly greater percent decrease in EF (+6+/-0.02 vs.-10.5+/-0.03, p = 0.005) and percent fractional shortening (+7+/-0.03 vs. -11+/-0.07, p = 0.0 15), and an increase in LV end systolic volume (-12+/-0.06 vs. +39+/-0.24, p = 0.011). These data suggest a reduction in cardiac function that relates to mission duration. As the changes in blood pressure and circulating blood volume (9% - 12%) are reported to be similar after short and long duration flights, the drop in EF after longer spaceflights is likely due to a decrease in cardiac function rather than altered blood volume.

Fritsch-Yelle, Janice M.↗
NASA NTRS2006

Skeletal Recovery Following Long-Duration Spaceflight Missions as Determined by Preflight and Postflight DXA Scans of 45 Crew Members

Introduction: The loss of bone mineral in astronauts during spaceflight has been investigated throughout the more than 40 years of bone research in space. Consequently, it is a medical requirement at NASA that changes in bone mass be monitored in crew members by measurements of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). This report is the first to evaluate medical data to address the recovery of bone mineral that is lost during spaceflight. Methods: DXA scans are performed before and after flight in astronauts who serve on long-duration missions (4-6 months) to ensure that medical standards for flight certification are met, to evaluate the effects of spaceflight and to monitor the restoration to preflight BMD status after return to Earth. Through cooperative agreements with the Russian Space Agency, the Bone and Mineral Lab at NASA Johnson Space Center (Houston, TX), also had access to BMD data from cosmonauts who had flown on long-duration missions yielding data from a total of 45 individual crew members. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing); plotted data were fitted to an exponential mathematical model that determined i) BMD change at day 0 after landing and ii) the number of days after which 50% of the lost bone was recovered ("Recovery Half-Life"). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. Results: In sum, averaged losses of bone mineral after spaceflight ranged between 2-9% for sites in the axial and appendicular skeleton. The fitted postflight BMD values predicted a 50% recovery of bone loss for all sites within 9 months.

Sibonga, J. D.↗
NASA NTRS1999

Behavior and Performance on Long-Duration Spaceflights: Evidence from Analogue Environments

Analyses of data collected in Antarctica since 1963 were conducted to identify features of behavior and performance likely to occur during long-duration missions in space.The influence of mission duration and station latitude on POMS mood scores was examined in 450 American men and women who overwintered in Antarctica between 1991 and 1998. The influence of crewmember social characteristics, personality traits, interpersonal needs, and station environments on measures of behavior and performance at the end of the austral winter was examined in 657 American men who overwintered between 1963 and 1974. Both data sets were used to examine the influence of crew social structure on individual performance. Results: Seasonal variations in mood appear to be associated with the altered diurnal cycle and psychological segmentation of the mission. Concurrent measures of personality, interpersonal needs, and coping styles are better predictors of depressed mood and peer-supervisor performance evaluations than baseline measures because of the unique features of the station social and physical environments and the absence of resources typically used to cope with stress elsewhere. Individuals in crews with a clique structure report significantly more depression, anxiety, anger, fatigue and confusion than individuals in crews with a core-periphery structure. Depressed mood is inversely associated with severity of station physical environment, supporting the existence of a positive or "salutogenic" effect for individuals seeking challenging experiences in extreme environments.

Palinkas, Lawrence A.↗
NASA NTRS1992

Early SEI milestones - Underwater habitats and Antarctic research outposts as analogs for long duration spaceflight and lunar and Mars outposts

The use of analog environments for space research is considered focusing on underwater habitats and Antarctic research sites as analogous settings to long-duration space flight. It is pointed out that the use of these earth analogs can provide engineers, scientists, and future crew members with critical 'mission' experience at a relatively low cost.

Rummel, John D.↗
NASA NTRS2011

Increased Intracranial Pressure and Visual Impairment Associated with Long-Duration Spaceflight

Although humans have been flying in space since the 1960s, more recent missions have revealed a new suite of physiological adaptations and consequences of space flight. Notably, 60% of long-duration crewmembers (ISS/MIR) and >25% of short-duration (Shuttle) crewmembers have reported subjective degradation in vision (based on debrief comments) (Gibson 2011). Decreased near-visual acuity was demonstrated in 46% of ISS/Mir and 21% of Shuttle crewmembers, resulting in a shift of up to 1-2 diopters in their refractive correction. It is likely that the recently revealed ophthalmic changes have been present since the first days of human space flight, but have been overlooked or attributed to other causations. The reported changes in vision have occurred at various time points throughout missions, with ranging degrees of visual degradation. Although some cases resolved upon return to Earth, several astronauts have not regained preflight visual acuity, indicating that the damage may be permanent. While observing these changes over the years, without other overt symptomology and with the given age range of the flying population, this has largely been attributed to an expected hyperopic shift due to aging. However, the availability of onboard analysis techniques, including visual acuity assessments, retinal imagery, and ultrasounds of the eye and optic nerve tracts, along with more detailed post-flight techniques, has led to the recent recognition of a wider syndrome. Along with vision changes, findings include flattening of the globe, swelling of the optic disc (papilledema), choroidal folds in the retina, swelling of the optic nerve sheath, and visual field defects. It is widely hypothesized that this constellation of findings may be explained by an elevation of intracranial pressure (ICP). Out of the 60% of long-duration astronauts that have reported a subjective degradation in vision, a subset (currently 10 astronauts) have developed this syndrome. The National Aeronautics and Space Administration (NASA) has made it a high priority to understand this syndrome and provide mitigation techniques to protect crewmembers from visual impairment. While there are many possible factors that could contribute to intracranial hypertension associated with spaceflight, the relative contribution of these, as well as the processes by which eye damage occurs as a result of intracranial hypertension, are not fully understood. The observed pathophysiological phenomena are extremely complex and it is likely that multiple factors contribute to their incidence, rather than one simple mechanism. This paper will define and examine the findings in detail, and expound upon the potential contributing factors and their relative contribution to this syndrome.

Marshall-Bowman, Karina↗
NASA NTRSDate not supplied

An Oculometric Standard to Assess the Performance of the Ocular System for Long Duration Spaceflight

Changes in the human brain, due to spaceflight, have been a challenge to the space program since its inception; a challenge that is becoming more acute as extended International Space Station (ISS) missions become routine, a return to crewed lunar exploration is about to begin, and a multi-year crewed trip to Mars is being planned. Determining the extent to which neurophysiological adaptations may adversely impact performance in operational tasks, assessing the full-time course of these changes, and identifying/mitigating any potential long-term health consequences are crucial steps required to enable safe crew-autonomous, long-duration, deep-space missions. Vision is the predominant perceptual sense used to guide cognition and motor control in humans. Thus, it is critical for the success of any future, long-duration mission to understand how long-term exposure to microgravity and to other stressors of spaceflight and their interactions, impact visual function. This is an especially challenging task given the small and disparate samples from which we have been and will be able to collect human performance data. NASA has recently been carefully tracking spaceflight-induced ophthalmic changes, driven in large part by the fluid shifts related to microgravity. In particular, a recent study of Optical Coherence Tomography (OCT) postflight measures revealed that more than two-thirds of US crew members experience significant increases in retinal thickness after 6month or longer ISS missions. Space Associated Neuro-ocular Syndrome (SANS) also includes visual acuity decrements and other ocular structural changes that could adversely impact in-flight performance as missions become longer. However, the impact of spaceflight on the visual system is not limited to the retina. Recent comparisons of pre-and post-flight brain images have revealed structural changes throughout the brain that implicate visual, visuomotor, and visual-cognitive pathways, consistent with observed functional impacts (e.g., decreased speed/accuracy/timing of fine goal-oriented movements). Current limitations on inflight testing make it very difficult to determine when and under what conditions SANS and other disruptions of human neurological subsystems arise. Currently, one cannot anticipate the time course and extent of impairment and recovery. This study addresses this knowledge gap by creating an integrated framework of the relevant existing literature on visual and oculomotor function during spaceflight with an eye towards complementing current structural measures of visuomotor impairment with new oculometric standard measures. Using eye-movement based visual function assessment and diagnostics would provide a valuable enhancement of crew health and performance monitoring in support of deepspace exploration.

Vision↗
NASA NTRS2014

Maiden Voyage of the Rodent Habitat on ISS: Opportunities for Investigating Molecular Mechanisms and Biomedical Consequences of Long Duration Spaceflight

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. The National Research Counsel’s Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored research. In preparation for the maiden voyage of the Rodent Habitat hardware and operations system (Rodent Research-1), and in close consultation with a Science Working Group comprised of veterinarians and experienced spaceflight investigators, we modified existing Animal Enclosure Module hardware, developed new hardware, operations, and science activities, and performed a series of ground-based verification tests. Preflight, ground based hardware tests included a simulation of SpaceX Dragon launch conditions (vibration and hypergravity) using the Transporter, and also two long-term biocompatibility tests (32 and 92 days) using the Habitat developed for long term housing on the ISS. The launch simulation test showed that adult mice housed in Transporter hardware adapted well, even if launch simulation was followed by a period of simulated weightlessness (via hind limb unloading). The biocompatibility tests demonstrated that the Habitat successfully supported animal health and also provided a useful video imaging system that enables frequent monitoring of animal health and behavior by veterinary and scientific experts on the ground, independent of ISS crew intervention. At the conclusion of all tests, mice were deemed healthy and suitable for conducting biological research. Additional preflight analyses of tissues preserved by freezing or fixation for gene expression analyses revealed that spleen and liver tissues recovered under conditions that simulated on-orbit activities yielded high quality RNA (RIN values 8-10) and liver enzyme activities and protein content (e.g. catalase). In addition, new methods were developed to optimize future science return by dissecting tissues post-euthanasia and storage. Various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for ~2-6 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and skeletal muscle) were of high RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrated the protocols developed for future flight experiments supported science return despite delayed preservation post-euthanasia or prolonged storage, and furthermore, that high-quality RNA samples from many different tissues can be recovered by dissection following prolonged storage of the tissue in situ at -80˚C. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 is dedicated to achieving both NASA validation and CASIS science objectives. Ground based control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis. The 10 mice for validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully on Oct 12 and 13, 2014, and the validation mice will reside on ISS for up to 30 days. In conclusion, new capability for long duration rodent research is under development, including in-flight sample collection (which avoids the complication of reentry); results obtained to date will be described. This new Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.

maiden voyage↗
NASA NTRSDate not supplied

Identifying Trends in Landing Profiles After Long Duration Spaceflight

BACKGROUND As NASA’s mission programs begin to shift from Low Earth Orbit (LEO) to planetary mission profiles, the importance of understanding the phenomena a human experience when returning from spaceflight is of increased importance. The purpose of this study was to assess trends across individuals in the symptoms experienced during the landing process of long duration ISS missions. METHODS Data for this study is an aggregation of mission level data from forms used by crew surgeons at R+0, electronic medical records, notes from weekly Space Medicine Operation Team meetings, records in the Shuttle Mission Data Archive, and data collected by research teams in the Human Research Program (HRP). Aggregated data was used in descriptive analysis of the trends in medical events and countermeasure use. The data was also used to identify high value targets for emphasis in on going surveillance efforts. RESULTS Completeness of reporting varied greatly over time and across missions dependent on information sources available for data extraction. Landing forms provided the most complete data but still missed or left unconfirmed, several, common symptoms, and countermeasures. Data aggregation did show to cover gaps within individual data sources. Commonly reported symptoms included nystagmus, vertigo, and nausea. Common protocols for fluid loading and meclizine are reflected within the data set. DISCUSSION The data set generated in this project provides a foundation that show how symptoms of astronauts as they return to Earth varies across the long duration ISS missions. While there is an abundance of information provided within the data set, there are still inconsistencies in reporting especially in the absence of the landing day form. Further data collection practices should be standardized to ease the burden on crew surgeons during R+0 exams and better collect high value variables.

Sam Jacobs↗
NASA NTRS2014

Improving Early Adaptation Following Long Duration Spaceflight by Enhancing Vestibular Information

Crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons after g-transitions. The transition from one sensorimotor state to another consists of two main mechanisms: strategic and plastic-adaptive and have been demonstrated in astronauts returning after long duration space flight. Strategic modifications represent "early adaptation" -immediate and transitory changes in control that are employed to deal with short-term changes in the environment. If these modifications are prolonged then plastic-adaptive changes are evoked that modify central nervous system function, automating new behavioral responses. More importantly, this longer term adaptive recovery mechanism was significantly associated with their strategic ability to recover on the first day after return to Earth G. We are developing a method based on stochastic resonance (SR) to enhance information transfer by improving the brain's ability to detect vestibular signals especially when combined with balance training exercises for rapid improvement in functional skill, for standing and mobility. The countermeasure to improve post-flight balance and locomotor disturbances is a stimulus delivery system that is wearable/portable providing low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system (stochastic vestibular stimulation, SVS). The techniques for improving signal detection using SVS may thus provide additional information to improve such strategic abilities and thus help in significantly reducing the number of days required to recover functional performance to preflight levels after long duration space flight. We have conducted a series of studies to document the efficacy of SVS stimulation on balance/locomotion tasks on unstable surfaces and motion tracking tasks during intra-vestibular system conflicts. In an initial study, we showed that SVS improved overall balance performance while standing on an unstable surface indicating that SVS may be sufficient to provide a comprehensive countermeasure approach for improving postural stability. In a second study, we showed that SVS improved locomotor performance on a treadmill mounted on an oscillating platform indicating that SVS may also be used to maximize locomotor performance during walking in unstable environments. In a third study, SVS was evaluated during an otolith-canal conflict scenario in a variable radius centrifuge at low frequency of oscillation (0.1 Hz) on both eye movements and perceptual responses (using a joystick) to track imposed oscillations. The variable radius centrifuge provides a selective tilting sensation that is detectable only by the otolith organs providing conflicting information from the canal organs of the vestibular system (intra-vestibular conflict). Results show that SVS significantly reduced the timing difference between both the eye movement responses as well as the perceptual tracking responses with respect to the imposed tilt sensations. These results indicate that SVS can improve performance in sensory conflict scenarios like that experienced during space flight. Such a SR countermeasure will act synergistically along with the pre-and in-flight adaptability training protocols providing an integrated, multi-disciplinary countermeasure capable of fulfilling multiple requirements making it a comprehensive and cost effective countermeasure approach to enhance sensorimotor capabilities following long-duration space flight.

Mulavara, Ajitkumar↗
NASA NTRS2008

Adaptation of the Skeletal System during Long-duration Spaceflight

This review will highlight evidence from crew members flown on space missions greater than 90 days to suggest that the adaptations of the skeletal system to mechanical unloading may predispose crew members to an accelerated onset of osteoporosis after return to Earth. By definition, osteoporosis is a skeletal disorder - characterized by low bone mineral density and structural deterioration - that reduces the ability of bones to resist fracture under the loading of normal daily activities. Involutional or agerelated osteoporosis is readily recognized as a syndrome afflicting the elderly population because of the insipid and asymptomatic nature of bone loss that does not typically manifest as fractures until after age approximately 60. It is not the thesis of this review to suggest that spaceflight-induced bone loss is similar to bone loss induced by metabolic bone disease; rather this review draws parallels between the rapid and earlier loss in females that occurs with menopause and the rapid bone loss in middle-aged crew members that occurs with spaceflight unloading and how the cumulative effects of spaceflight and ageing could be detrimental, particularly if skeletal effects are totally or partially irreversible. In brief, this report will provide detailed evidence that long-duration crew members, exposed to the weightlessness of space for the typical long-duration (4-6 months) mission on Mir or the International Space Station -- 1. Display bone resorption that is aggressive, that targets normally weight-bearing skeletal sites, that is uncoupled to bone formation and that results in areal BMD deficits that can range between 6-20% of preflight BMD; 2. Display compartment-specific declines in volumetric BMD in the proximal femur (a skeletal site of clinical interest) that significantly reduces its compressive and bending strength and which may account for the loss in hip bone strength (i.e., force to failure); 3. Recover BMD over a post-flight time period that exceeds spaceflight exposure but for which the restoration of whole bone strength remains an open issue and may involve structural alteration; and 4. Display risk factors for bone loss -- such as the negative calcium balance and down-regulated calcium-regulating hormones in response to bone atrophy -- that can be compounded by the constraints of conducting mission operations (inability to provide essential nutrients and vitamins). The full characterization of the skeletal response to mechanical unloading in space is not complete. In particular, countermeasures used to date have been inadequate and it is not yet known whether more appropriate countermeasures can prevent the changes in bone that have been found in previous flights, knowledge gaps related to the effects of prolonged (greater than or equal to 6 months) space exposure and to partial gravity environments are substantial, and longitudinal measurements on crew members after spaceflight are required to assess the full impact on skeletal recovery.

Sibonga, Jean D.↗
NASA NTRS2007

Bisphosphonate Treatment: Risk Management in Long Duration Spaceflight

Bisphosphonates are a class of pharmaceuticals used to treat diverse bone disorders such as osteoporosis, Paget's disease, and multiple myeloma. They constitute a class of drugs which adhere to bony surfaces and interfere with the resorptive activity of osteoclasts. They also represent a potential countermeasure towards the loss of bone mass experienced by astronauts during spaceflight. Recently, the medical literature has revealed cases of osteonecrosis of the jaw in individuals receiving intravenous bisphosphonate therapy with a smaller number of cases occurring in individuals receiving the oral form of the medication. Risk management for long duration missions requires consideration of mission success and lifetime health care of astronauts. We performed MEDLINE and PubMed searches (1966 December 2006) using the following keywords: osteonecrosis, jaw, bisphosphonates. Additional references were obtained from the citations of the retrieved articles. Injectable bisphosphonates such as pamidronate and zoledronic acid have been highlighted recently in the literature due to a possible link with osteonecrosis of the jaw. The mechanism of action remains unclear but may be linked to physiologic microdamage in the jawbones resulting from suppression of bone metabolism. The most predisposing factors appear to be the type and dose of bisphosphonate used, a history of dental surgery, trauma, and/or dental infection. In addition, patients diagnosed with a malignancy such as breast cancer or multiple myeloma, who have been on intravenous bisphosphonate therapy for several months seem to be at increased risk. The use of oral bisphosphonates appears to place patients more at risk from acute events such as gastrointestinal tract injury or perforation. Although some studies report little to no increase in GI events compared to placebo, we must remember that in microgravity, astronauts may be unable to comply with medication instructions. They may have difficulty remaining upright for the required 30-45 minutes post-ingestion. We are currently unaware if this inability to comply with instructions on the package insert may lead to an increased risk for GI events. There is a potential long-term complication that resides with both forms of bisphosphonate therapy. In order to repair normally occurring physiologic microdamage to bone, both osteoclastic resorption and osteoblastic bone deposition must be functional. Controversy exists in the literature regarding whether prolonged use of bisphosphonates may lead to the suppression of bone turnover and accumulation of microdamage. Bisphosphonates are a powerful class of drugs that suppress bone turnover, but may cause serious adverse clinical events such as gastrointestinal tract injury or osteonecrosis of the jaw. Unfortunately, little to no data exists currently which may help us provide answers regarding the risks of their use in a healthy astronaut cohort. While controversy exists in the literature regarding their mechanism and long-term consequences, the potential mission impact or lifetime health care impact of an adverse clinical event resulting from bisphosphonate therapy must be considered.

Fogarty, Jennifer A.↗
NASA NTRS2010

Comparison of Postural Recovery Following Short and Long Duration Spaceflights

INTRODUCTION: Post-flight postural ataxia reflects adaptive changes to vestibulo-spinal reflexes and control strategies adopted for movement in weightlessness. Quantitative measures obtained during computerized dynamic posturography (CDP) from US and Russian programs provide insight into the effect of spaceflight duration in terms of both the initial decrements and recovery of postural stability. METHODS: CDP was obtained on 117 crewmembers following Shuttle flights lasting 4-17 days, and on 64 crewmembers following long-duration missions lasting 48-380 days. Although the number and timing of sessions varied, the goal was to characterize postural recovery pooling similar measures from different research and flight medicine programs. This report focuses on eyes closed, head erect conditions with either a fixed or sway-referenced base of support. A smaller subset of subjects repeated the sway-referenced condition while making pitch head movements (+/- 20deg at 0.33Hz). Equilibrium scores were derived from peak-to-peak anterior-posterior sway. Fall probability was modeled using Bayesian statistical methods to estimate parameters of a logit function. RESULTS: The standard Romberg condition was the least sensitive. Longer duration flights led to larger decrements in stability with sway-reference support during the first 1-2 days, although the timecourse of recovery was similar across flight duration with head erect. Head movements led to increased incidence of falls during the first week, with a significantly longer recovery following long duration flights. CONCLUSIONS: The diagnostic assessment of postural instability, and differences in the timecourse of postural recovery between short and long flight durations, are more pronounced during unstable support conditions requiring active head movements.

Wood, S. J.↗
NASA NTRS2014

Effects of Long Duration Spaceflight on Venous and Arterial Compliance

The visual impairment and intracranial pressure syndrome (VIIP) is a newly described space flight-associated medical condition made up of a constellation of symptoms affecting at least 34% of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures, and is thought to be related to elevated intracranial pressure secondary to space flightinduced cephalad fluid shifts. Loss of visual acuity could be a significant threat to crew health and performance and may be suggestive of other adaptations with implications for years post-flight. Our primary objective is to determine whether vascular compliance is altered by space flight and whether such adaptations are related to the incidence of VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no space flight experience, in astronauts before, during, and after space flight, and in bed rest subjects with conditions similar to space flight. Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archive to determine which factors might be predictive of the development of VIIP. The project will be conducted in four separate but related parts. To understand the baseline condition of astronauts without any prior space flight experience, we will study 10 astronauts who have never flown in space by performing a comprehensive evaluation of the vasculature of the head, neck and eyes. Hemodynamic data (stroke volume and blood pressure), ocular (tonometry and ocular ultrasound), venous and arterial parameters will be acquired across a range of tilt angles (20, 10, 0, -10, -20 degrees). Vessels to be studied include the temporal, jugular, and vertebral veins and the cerebral, carotid and vertebral arteries. Ophthalmic data from the annual physical will be obtained through data sharing. To examine the relation between vascular compliance in the head and neck and the development of VIIP after a long duration space flight, we will study 10 astronauts before, during, and after long-duration ISS missions. Pre- and post-flight testing will be identical to that described above. During flight, images of the same vessels of interest will be obtained for later analysis. Ophthalmic data including VIIP scores will be obtained through data sharing from medically-required tests. To investigate the effects of age and elevated sodium intake, two potential contributors to VIIP, we will study 24 men (in two age groups: 25-35 and 45-55) during a 14 day 6deg head-down bed rest, a well-accepted analog of space flight. Standard NASA bed rest conditions will be maintained except for dietary sodium. Sodium intake will be similar to that of ISS astronauts, which is higher than consumed in previous bed rest studies. Pre- and post-bed rest testing procedures will be identical to the testing protocol described above for astronauts. Ophthalmic testing (optical coherence tomography, fundoscopy, and tonometry) will be conducted on the same day that vascular compliance measures are obtained. To identify parameters that may relate to an increase in an astronaut's susceptibility to developing VIIP, we will use data mining techniques to evaluate astronaut data obtained from the LSAH. Medical history, family history, space flight history and its related exposures, and history of high performance jet aircraft exposure will be examined for their potential relationship to ocular data. We hypothesize that the cephalad fluid shift induced by space flight will result in structural and functional adaptations in head and neck vessels leading to decreased vascular compliance and related to the development of VIIP symptoms. Further, although VIIP has not been observed in previous bed rest studies, we hypothesize that an elevated sodium intake will increase the incidence of VIIP symptoms in this space flight analog. Finally, we hypothesize that data mining analyses will reveal relationships between health history, previous exposures (including space flight and high performance aircraft), and the development of VIIP in the astronaut population.

Ribeiro, L. C.↗