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All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Decorin and biglycan of normal and pathologic human corneas

PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

Non-NASA Center↗
NASA NTRS1996

Characterization of the early pulmonary inflammatory response associated with PTFE fume exposure

Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (approximately 18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460 degrees C for 15 min at an exposure concentration of 5 x 10(5) particles/cm3, equivalent to approximately 50 micrograms/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60-85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-alpha (TNF alpha) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls. In situ sections were hybridized with 33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNF alpha. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNF alpha. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.

Non-NASA Center↗
NASA NTRS1994

Recent bed rest results and countermeasure development at NASA

Bedrest studies of normal subjects provide opportunities to understand physiologic responses to supine posture and inactivity. Furthermore, head-down tilt has been a valuable procedure to investigate adaptation to microgravity and development of countermeasures to maintain the health and well-being of humans during space-flight. Recent bedrest experiments at NASA have ranged in duration from a few hours to 17 weeks. Acute studies of 6 degrees head-down tilt indicate that elevation of capillary blood pressure from 28 to 34 mm Hg and increased capillary perfusion in tissues of the head cause facial and intracranial edema. Intracranial pressure increases from 2 to 17 mm Hg going from upright posture to 6 degrees head-down tilt. Microvessels of the head have a low capacity to constrict and diminish local perfusion. Elevation of blood and tissue fluid pressures/flow in the head may also explain the higher headward bone density associated with long-term head-down tilt. These mechanistic studies of head-down tilt, along with a better understanding of the relative stresses involved with upright posture and lower body negative pressure, have facilitated development of suitable physiologic countermeasures to maintain astronaut health during microgravity. Presently no exercise hardware is available to provide a blood pressure gradient from head to feet in space. However, recent studies in our laboratory suggest that treadmill exercise using a graded lower-body compression suit and 100 mmHg lower body negative pressure provides equivalent or greater physiologic stress than similar upright exercise on Earth. Therefore, exercise within a lower body negative pressure chamber may provide a cost-effective and simple countermeasure to maintain the cardiovascular and neuro-musculoskeletal systems of astronauts during long-duration flight.

manned↗
NASA NTRS1992

Ventilation-perfusion matching during exercise

In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

Non-NASA Center↗
NASA NTRS1990

Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

NASA Experiment Number COS 1887-6↗
NASA NTRS2000

Pulmonary Toxicity of Simulated Lunar and Martian Dusts Intratracheally Instilled into Mice

The National Aeronautics and Space Administration (NASA) is contemplating sending humans to Mars and to the Moon for further exploration. Equipment designated for these extraterrestrial bases will require testing in simulated Martian or lunar environments. The properties of Hawaiian and San Francisco Mountain volcanic ashes make them suitable to be used in these test environments as Martian and lunar dust simulants, respectively. The present toxicity study was conducted to address NASA's concern about the health risk of dust exposures in the test facilities. In addition, the results obtained on these simulants can be used to design a toxicity study of actual moon dust and Martian dust, which will probably be available in a few years. Respirable portions of lunar soil simulant (LSS) and Martian soil simulant (MSS) were separated from their respective raw materials. These soil simulants, together- with fine titanium dioxide (negative control for fibrogenesis in mice), and crystalline silica (positive control) were each intratracheally instilled in saline to groups of 4 male mice (C57BL/6J, 2-3 months old) at 0.1 mg/mouse (LD) or lmg/mouse (HD). The lungs were harvested 7 or 90 days after the single dust treatment for histopathological examination. Lungs of the LSS-LD groups on either the 7- or 90-day study showed no evidence of inflammation, edema, or fibrosis. Clumps of particles and an increased number of macrophages, visible in the lungs examined after 7 days, were absent after 90 days. The LSS-HD-7d group showed mild to moderate alveolitis with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of chronic inflammation: septal thickening, mild perivascular and peribronchiolar inflammation, mild alveolitis and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lungs of the MSS-LD-7d group revealed mild focal intraalveolar inflammation with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The MSS-LD-90d group showed PLMs and scattered foci of mild fibrosis. The MSS-HD-7d group showed large foci of PLMs, intraalveolar debris, mild to moderate focal alveolitis, and mild to moderate perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild to moderate alveolitis and fibrosis. To mimic the oxidative and reactive properties of Martian surface dust in the test animals, groups of 4 mice were exposed to ozone (0.5 ppm for 3 hours) prior to instillation of the MSS. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The O3-MSS-HD-90d group had wide spread intraalveolar debris, focal moderate alveolitis and fibrosis. The results for the titanium dioxide and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic injury to the lungs was TiO2<LSS<MSS<MSS+O3<quartz. In general, the toxic responses increased with the increase of dust burden in the lung. Except for TiO2, the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion.

Lam, Chiu-Wing↗
NASA NTRS2010

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗
NASA NTRS2011

Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, and a decrease in leg diameter. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and during preload reduction introduced with thigh occlusion cuffs used as a counter-measure device (Braslet cuffs) measured by cardiac and vascular ultrasound examinations. Methods: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 +/- 46.days after launch (mean +/- SD; 33 - 185). Twenty Seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs. Results: Non-physicians performed diagnostic-quality cardiac and vascular ultrasound examinations using remote guidance. Three of 27 combinations of maneuvers and Braslet or Braslet alone were identified as being significant changed when compared to baseline. Eleven of 81 differences between combinations of Mueller, Valsalva or baseline were significant and related to cardiac preload reduction or increase in lower extremity venous volume. Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an invaluable tool in determining the volume status of the cardiac patient at the 'microgravity bedside'.

Hamilton, Douglas↗
NASA NTRS2011

Effects and Responses to Spaceflight in the Mouse Retina

Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to evaluate the impact of the stress response on retinal health.

Zanello, Susana B.↗
NASA NTRS2011

Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

Reports of astronauts visual changes raised concern about ocular health during long-duration spaceflight. Some of these findings included hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, hypotheses speculate that hypertension in the brain caused by cephalad fluid shifts during spaceflight is a possible mechanism for these ocular changes. Head-down tilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. In addition, previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP). For these reasons, vision monitoring of HDT bed rest subjects was implemented for NASA bed rest studies. Subjects selected for these studies were healthy adults (14 males and 5 females). Average age was 37.5 plus or minus 9.1 years, weight was 77.4 plus or minus 11.3 Kg, and height was 173.4 plus or minus 7.2 14 cm. Controlled conditions followed for all NASA bed rest studies were implemented. These conditions included factors such as eating a standardized diet, maintaining a strict sleep wake cycle, and remaining in bed for 24 hours each day. In one study, subjects maintained a horizontal (0 degree) position while in bed and were exercised six days per week with an integrated resistance and aerobic training (iRAT) program. In the other study, subjects were placed at 6 degrees HDT while in bed and did not engage in exercise. All subjects underwent pre- and post bed rest vision testing. While the battery of vision tests for each study was not identical, measures common to both studies will be presented. These measures included IOP and measures that provided an indication of optic disc swelling as derived from optical coherence tomography (OCT) testing: average retinal nerve fiber layer (RNFL) thickness (millimeters), disc area (square millimeters), rim area (square millimters), and average cup to disc (C/D) ratio. For all measures, there was no significant difference between subject groups for pre-bed rest testing. Post bed rest values also remained similar between groups. Comparison of pre- to post bed rest testing within each group did not demonstrate any statistical differences. These preliminary results from 14-day bed rest studies suggest that the combination of exercise and horizontal bed rest as compared to 6 degrees HDT bed rest did not produce differences in the ocular response with regard to IOP and optic disc parameters. The ocular measures reported here only included pre- and post bed rest time points. Further investigation is needed to examine both the acute response and long term adaptation of structural and functional ocular parameters in the bed rest platform and determine its usefulness for studying spaceflight phenomena. From a clinical perspective, the ability to study ocular responses in the controlled environment of the bed rest platform can provide valuable information for the care of patients restricted to bed rest.

Cromwell, R. L.↗
NASA NTRS2011

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using "Braslet-M" Occlusion Cuffs

BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers as measured by cardiac and vascular ultrasound in a baseline microgravity steady state, and under the influence of thigh occlusion cuffs (Braslet cuffs). METHODS: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 46 days after launch (mean SD; 33 - 185). 27 cardiac and vascular parameters were obtained under three respiratory conditions (baseline, Valsalva, and Mueller) before and after tightening of the Braslet cuffs for a total of 162 data points per session. The quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by Investigators from the NASA Telescience Center in Houston, TX, USA. RESULTS: Fourteen of the 81 measured conditions were significantly different with Braslet application and were apparently related to cardiac preload reduction or increase in the venous volume sequestered in the lower extremity. These changes represented 10 of the 27 parameters measured. In secondary analysis, 7 of the 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression, with a total of 11 differences. CONCLUSIONS: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts proportionate measurable effects on cardiac performance in microgravity. Ultrasound techniques measuring the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient in microgravity.

Hamilton, D. R.↗
NASA NTRS2011

A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown.

Westby, Christian M.↗
NASA NTRS2012

Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

Reports of astronauts' visual changes have raised concern about ocular health during long-duration spaceflight. Some of these findings include globe flattening with hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, it is hypothesized that, in predisposed individuals, hypertension in the brain may follow cephalad fluid shifts during spaceflight. This possible mechanism of ocular changes may also apply to analogous cases of idiopathic intracranial hypertension (IIH) or pseudotumor cerebri on Earth patients. Head-down t ilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. Previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP) but the conditions of bed rest varied among experiments, making it difficult to compare data and draw conclusions. For these reasons, vision evaluation of bed rest subjects was implemented for NASA bed rest studies since 2010, in an attempt to monitor vision health in subjects subjected to bed rest. Vision monitoring is thus currently performed in all NASA-conducted bed rest campaigns

Cromwell, Ronita L.↗
NASA NTRS2012

An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment

When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model.

Nelson, Emily S.↗
NASA NTRS2013

Computational Modeling of Cephalad Fluid Shift for Application to Microgravity-Induced Visual Impairment

An improved understanding of spaceflight-induced ocular pathology, including the loss of visual acuity, globe flattening, optic disk edema and distension of the optic nerve and optic nerve sheath, is of keen interest to space medicine. Cephalad fluid shift causes a profoundly altered distribution of fluid within the compartments of the head and body, and may indirectly generate phenomena that are biomechanically relevant to visual function, such as choroidal engorgement, compromised drainage of blood and cerebrospinal fluid (CSF), and altered translaminar pressure gradient posterior to the eye. The experimental body of evidence with respect to the consequences of fluid shift has not yet been able to provide a definitive picture of the sequence of events. On earth, elevated intracranial pressure (ICP) is associated with idiopathic intracranial hypertension (IIH), which can produce ocular pathologies that look similar to those seen in some astronauts returning from long-duration flight. However, the clinically observable features of the Visual Impairment and Intracranial Pressure (VIIP) syndrome in space and IIH on earth are not entirely consistent. Moreover, there are at present no experimental measurements of ICP in microgravity. By its very nature, physiological measurements in spaceflight are sparse, and the space environment does not lend itself to well-controlled experiments. In the absence of such data, numerical modeling can play a role in the investigation of biomechanical causal pathways that are suspected of involvement in VIIP. In this work, we describe the conceptual framework for modeling the altered compartmental fluid distribution that represents an equilibrium fluid distribution resulting from the loss of hydrostatic pressure gradient.

Nelson, Emily S.↗
NASA NTRS2014

Facial Soft Tissue Measurement in Microgravity-induces Fluid Shifts

Fluid shifts are a well‐known phenomenon in microgravity, and one result is facial edema. Objective measurement of tissue thickness in a standardized location could provide a correlate with the severity of the fluid shift. Previous studies of forehead tissue thickness (TTf) suggest that when exposed to environments that cause fluid shifts, including hypergravity, head‐down tilt, and high‐altitude/lowpressure, TTf changes in a consistent and measurable fashion. However, the technique in past studies is not well described or standardized. The International Space Station (ISS) houses an ultrasound (US) system capable of accurate sub‐millimeter measurements of TTf. We undertook to measure TTf during long‐duration space flight using a new accurate, repeatable and transferable technique. Methods: In‐flight and post‐flight B‐mode ultrasound images of a single astronaut's facial soft tissues were obtained using a Vivid‐q US system with a 12L‐RS high‐frequency linear array probe (General Electric, USA). Strictly mid‐sagittal images were obtained involving the lower frontal bone, the nasofrontal angle, and the osseo‐cartilaginous junction below. Single images were chosen for comparison that contained identical views of the bony landmarks and identical acoustical interface between the probe and skin. Using Gingko CADx DICOM viewing software, soft tissue thickness was measured at a right angle to the most prominent point of the inferior frontal bone to the epidermis. Four independent thickness measurements were made. Conclusions: Forehead tissue thickness measurement by ultrasound in microgravity is feasible, and our data suggest a decrease in tissue thickness upon return from microgravity environment, which is likely related to the cessation of fluid shifts. Further study is warranted to standardize the technique with regard to the individual variability of the local anatomy in this area.

Marshburn, Thomas↗
NASA NTRS2014

High Performance EVA Glove Collaboration: Glove Injury Data Mining Effort

Human hands play a significant role during extravehicular activity (EVA) missions and Neutral Buoyancy Lab (NBL) training events, as they are needed for translating and performing tasks in the weightless environment. It is because of this high frequency usage that hand- and arm-related injuries and discomfort are known to occur during training in the NBL and while conducting EVAs. Hand-related injuries and discomforts have been occurring to crewmembers since the days of Apollo. While there have been numerous engineering changes to the glove design, hand-related issues still persist. The primary objectives of this study are therefore to: 1) document all known EVA glove-related injuries and the circumstances of these incidents, 2) determine likely risk factors, and 3) recommend ergonomic mitigations or design strategies that can be implemented in the current and future glove designs. METHODS: The investigator team conducted an initial set of literature reviews, data mining of Lifetime Surveillance of Astronaut Health (LSAH) databases, and data distribution analyses to understand the ergonomic issues related to glove-related injuries and discomforts. The investigation focused on the injuries and discomforts of U.S. crewmembers who had worn pressurized suits and experienced glove-related incidents during the 1980 to 2010 time frame, either during training or on-orbit EVA. In addition to data mining of the LSAH database, the other objective of the study was to find complimentary sources of information such as training experience, EVA experience, suit-related sizing data, and hand-arm anthropometric data to be tied to the injury data from LSAH. RESULTS: Past studies indicated that the hand was the most frequently injured part of the body during both EVA and NBL training. This study effort thus focused primarily on crew training data in the NBL between 2002 and 2010. Of the 87 recorded training incidents, 19 occurred to women and 68 to men. While crew ages ranged from thirties to fifties, the age category most affected was in the forties range. Incident rate calculations (incidents per 100 training runs) revealed that the 2002, 2003, and 2004 time periods registered the highest reported incident rate levels (3.4, 6.1, and 4.1 respectively) when compared to the following years (all ≤ 1.0). In addition to general hand-arm discomfort being the highest reported result from training, specific types of hand injuries or symptoms included erythema, fingernail delamination, abrasions, muscle soreness/fatigue, paresthesia, bruising, blanching, and edema. Specific body locations most affected by hand injuries included the metacarpophalangeal joints, fingernails, finger crotches, fingers in general, interphalangeal joints, and fingertips. Causes of injuries reported in the LSAH data were primarily attributed to the forces that the gloved hands were exposed to due to hand intensive tasks and/or poor glove sizing. DISCUSSION: Although the age data indicate that most injuries are reported by male crewmembers in their forties, that is also the dominant gender and age range of most EVA crew therefore it is not an unexpected finding. Age and gender analysis will continue as more details on the uninjured population is accrued. While there is a reasonable mechanism to link training quantity to injury, the results were inconsistent and point to the need for a consistent method of suit-related injury screening and documentation. For instance, the high-incident rate levels for the years 2002 to 2004 could be attributed to a comprehensive medical review of crewmembers post-NBL EVA training that occurred from July 19, 2002 to January 16, 2004. Furthermore, there could have been increased awareness from an investigation at the NBL. These investigations may have temporarily increased the fidelity of reported injuries and discomforts during these dates as compared to surrounding years, when injury signs and symptom were no longer actively being investigated but rather voluntarily reported. Data mining for possible mechanistic factors continues and includes more detailed training timelines, hand anthropometry, and suit sizing information. The limited published data looking at hand-arm anthropometry correlated hand-anthropometry metrics with injuries stemming from glove design and operation. Future work will include further evaluation of body sizing and fit in relation to hand injury incidents.

Reid, C. R.↗
NASA NTRS2015

Prospective Observational Study of Ocular Health in ISS Crews - The Ocular Health Study

The Visual Impairment Intracranial Pressure (VIIP) syndrome is currently NASA's number one human space flight risk. The syndrome, which is related to microgravity exposure, manifests with changes in visual acuity (hyperopic shifts, scotomas), changes in eye structure (optic disc edema, choroidal folds, cotton wool spots, globe flattening, and dilated optic nerve sheaths), and in some cases with documented increased intracranial pressure (ICP) postflight. While the eye appears to be the main affected end organ of this syndrome, the ocular effects are thought to be related to underlying changes in the vascular system and the central nervous system. The leading hypotheses for the development of VIIP involve microgravity-induced head-ward fluid shifts along with a loss of gravity-assisted drainage of venous blood from the brain, leading to cephalic congestion, decreased CSF resorption and increased ICP. Since 70% of ISS crewmembers have manifested clinical signs or symptoms of the VIIP syndrome, it is assumed that the majority have some degree of ICP elevation in-flight compared to the ground. Prolonged elevations of ICP can cause long-term reduced visual acuity and loss of peripheral visual fields, and have been reported to cause mild cognitive impairment in the analog terrestrial population of Idiopathic Intracranial Hypertension (IIH). These potentially irreversible health consequences underscore the importance of identifying the factors that lead to this syndrome and mitigating them.

Otto, C.↗