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NASA NTRS1993

Physiologic mechanisms of circulatory and body fluid losses in weightlessness identified by mathematical modeling

Central volume expansion due to fluid shifts in weightlessness is believed to activate adaptive reflexes which ultimately result in a reduction of the total circulating blood volume. However, the flight data suggests that a central volume overdistention does not persist, in which case some other factor or factors must be responsible for body fluid losses. We used a computer simulation to test the hypothesis that factors other than central volume overdistention are involved in the loss of blood volume and other body fluid volumes observed in weightlessness and in weightless simulations. Additionally, the simulation was used to identify these factors. The results predict that atrial volumes and pressures return to their prebedrest baseline values within the first day of exposure to head down tilt (HDT) as the blood volume is reduced by an elevated urine formation. They indicate that the mechanisms for large and prolonged body fluid losses in weightlessness is red cell hemoconcentration that elevates blood viscosity and peripheral resistance, thereby lowering capillary pressure. This causes a prolonged alteration of the balance of Starling forces, depressing the extracellular fluid volume until the hematocrit is returned to normal through a reduction of the red cell mass, which also allows some restoration of the plasma volume. We conclude that the red cell mass becomes the physiologic driver for a large 'undershoot' of the body fluid volumes after the normalization of atrial volumes and pressures.

Simanonok, K. E.↗

NASA NTRS2010

Space Flight-Induced Intracranial Hypertension: An Ophthalmic Review

Background: Although physiologic and pathologic changes associated with microgravity exposure have been studied extensively, the effect of this environment on the eye is largely unknown. Over the last several years, NASA s Space Medicine Division has documented astronauts presenting with varying degrees of disc edema, globe flattening, choroidal folds, cotton wool spots, and hyperopic shifts after long-duration space flight. Methods: Before and after long-duration space flight, six astronauts underwent complete eye examinations to include cycloplegic and/or manifest refraction and fundus photography. Five of these astronauts had Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI) performed following their missions. Results: Following exposure to space flight of approximately 6-months duration, six astronauts had neuro-ophthalmic findings. These consisted of disc edema in four astronauts, globe flattening in four astronauts, choroidal folds in four astronauts, cotton wool spots in three astronauts, nerve fiber layer thickening by OCT in five astronauts, and decreased near vision in five astronauts. Four of the astronauts with near vision complaints had a hyperopic shift equal to or greater than + 0.50D between pre- and post-mission spherical equivalent refraction in one or both eyes (range +0.50D to +1.50D). These same four had globe flattening by MRI. Conclusions: The findings we describe may have resulted from a rise in intracranial pressure caused by microgravity fluid shifts, and could represent parts of a spectrum of ocular and cerebral responses to extended microgravity.

Gibson, Charles Robert↗

NASA NTRS2025

Effect of Strict Head Down Tilt Bedrest on Pituitary Gland Height

BACKGROUND Pituitary gland deformity and loss of pituitary height have been identified in astronauts postflight, hypothesized to be related to increased intracranial pressure or intracranial pressure pulsatility exposure from prolonged weightlessness. Microgravity-induced chronic headward fluid shift has been suggested as a root cause of intracranial compliance changes leading to altered intracranial pressure dynamics. Elevated intracranial pressure or pressure pulsatility is theorized to promote the development of an arachnoid diverticulum, which herniates into the pituitary fossa via a defect in the diaphragma sellae compressing the pituitary gland. We aimed to determine if chronic headward fluid induced by strict head-down tilt bed rest (HDTBR) can cause similar quantitative changes in pituitary gland height. METHODS Control group data from two 6-degree HDTBR studies were analyzed (SANS CM and AGBRESA). The AGBRESA study collected MRI data at Baseline, 14 days into HDTBR (HDTBR-14), 52 days into HDTBR (HDTBR-52), and three days into Recovery (R+ 3) and included eight healthy adults (2 women), age = 33 ± 8 years. The SANS CM collected MRI data at Baseline, 15 days into HDTBR (HDTBR-15), 29 days into HDTBR (HDTBR-29), and 12 days into Recovery (R+12) and included twelve healthy adults (4 women), age = 34 ± 9 years. Pituitary gland height was evaluated using a sagittal, 3D T1-MPRAGE sequence obtained on a dedicated 3T Siemens Biograph MRI scanner using a 32-channel head coil. Following the reconstruction of a true orthogonal sagittal plane of the pituitary gland using a 3D multiplanar reconstruction tool (Horosproject.org), the anterior pituitary mid-gland height at the pituitary stalk level was quantified according to the methodology described by Kramer et al. . A paired t-test was used to evaluate changes from the baseline measurements. FINDINGS The mean height of the pituitary gland at baseline was 6.5 ± 1.7 mm (AGBRESA) and 5.7 ± 1.6 mm (SANS CM). From baseline measurements, the SANS CM STUDY data showed a decrease in mean pituitary height of 0.3 mm (p=.011) at HDTBR-15, 0.5 mm at HDTBR-29 (p<.001) and 0.2 mm at R+12 (p=.02). From baseline measurements, the AGBRESA data showed a decrease in mean pituitary height of 0.3 mm (p=.06) at HDTBR-14, 0.6 mm at HDTBR-52 (p<.002) and 0.2 mm at R+3 (p=.13). CONCLUSION HDTBR results in progressive loss of pituitary height, which is most severe with the longest HDTBR exposure. Early pituitary height loss was the same at HDTBR-14 (AGBRESA) and HDTBR-15 (SANS CM). Residual pituitary height loss was the same at R+12 and R+3 but only significant in the latter (SANS CM). The degree of pituitary height loss at HDTBR-52 replicates the 0.6 mm height loss found in long-duration astronauts after approximately six months of microgravity exposure (p<.01, preflight mean height=5.9 mm). The hormonal effects of pituitary height loss are unknown in astronauts and HDTBR subjects and should be investigated in future studies. Future work will examine the individual variability in the loss of pituitary gland height and whether those changes are associated with other SANS findings, such as optic disc edema.

L A Kramer↗

NASA NTRSDate not supplied

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗

NASA NTRS1983

Current concepts of space flight induced changes in hormonal control of fluid and electrolyte metabolism

A systematic analysis of body fluid and renal dynamics during simulated space flight (head-down bedrest) was undertaken to increase understanding of the physiologic effects of acute cephalad fluid shifts. The earliest effects were increases in central venous pressure and decreases in plasma aldosterone, epinephrine and norepinephrine and glomerular filtration rate, 2 h after the beginning of bedrest. Decreases in plasma angiotensin I at 6 h may have resulted from the increased effective pressure and decreased sympathetic activity seen earlier in bedrest. The early decrease in aldosterone and ADH is thought to contribute to an increase, by 6 h, in urinary excretion of salt and water. Fluid and electrolyte losses occur during space flight, and analysis of body fluids from Space Shuttle crewmembers has indicated that conservation of these substances is begun almost immediately upon cessation of weightlessness. Operational medicine measures to counteract dehydration and electrolyte loss resulted in a less extreme physiologic response to the flight.

Leach, C. S.↗

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.↗

NASA NTRS1985

Exercise thermoregulation in men after 6 hours of immersion

The present investigation is concerned with thermoregulation at rest and during exercise after water-immersion deconditioning, giving particular attention to the effects of fluid shifts and negative water balance on sweat rate and rectal temperature. Six healthy males 20-35 years old were used in the experiments. Rectal and mean skin temperature, skin heat conductance, heart rate, and total body sweat rate were measured during 70 min of supine leg exercise at 50 percent of peak O2 uptake. The data were taken after a 6-h control period in air and after immersion to the neck in water (34.5 C) for 6 h after overnight food and fluid restriction. Attention is given to end exercise heart rates and data during exercise. The obtained results suggest that, compared with control responses, the equilibrium level of core temperature during submaximal exercise is regulated at a higher level after immersion.

Greenleaf, J. E.↗

NASA NTRS2012

NASA's Current Evidence and Hypothesis for the Visual Impairment and Intracranial Pressure Risk

While 40 years of human spaceflight exploration has reported visual decrement to a certain extent in a subgroup of astronauts, recent data suggests that there is indeed a subset of crewmembers that experience refraction changes (hyperoptic shift), cotton wool spot formation, choroidal fold development, papilledema, optic nerve sheath distention and/or posterior globe flattening with varying degrees of severity and permanence. Pre and postflight ocular measures have identified a potential risk of permanent visual changes as a result of microgravity exposure, which has been defined as the Visual Impairment and Intracranial Pressure risk (VIIP). The combination of symptoms are referred to as the VIIP syndrome. It is thought that the ocular structural and optic nerve changes are caused by events precipitated by the cephalad fluid shift crewmembers experience during long-duration spaceflight. Three important systems, ocular, cardiovascular, and central nervous, seem to be involved in the development of symptoms, but the etiology is still under speculation. It is believed that some crewmembers are more susceptible to these changes due to genetic/anatomical predisposition or lifestyle (fitness) related factors. Future research will focus on determining the etiology of the VIIP syndrome and development of mechanisms to mitigate the spaceflight risk.

Otto, Christian A.↗

NASA NTRS1979

Early cardiovascular adaptation to simulated zero gravity

A study was conducted on five normal male volunteers (23-29 yr), under controlled conditions, to evaluate early adaptive responses to zero gravity. Specific objectives are (1) to characterize the hemodynamic, renal and hormonal responses to a central fluid shift, and (2) to compare data obtained during and after head-down tilt with corresponding data from actual space flight to validate tilt as a physiological model for simulation of zero gravity. Zero gravity is simulated by a 24-hr period of head-down tilt at 5 deg. The results suggest that hemodynamic adaptation occurs rapidly and is essentially accomplished by 6 hr, and that adaptation includes diuresis and reduction in blood volume. The validity of head-down tilt at 5 deg as an experimental model is established by comparing the results obtained with data from Apollo and Skylab astronauts on body fluid distributions and postflight responses to orthostatic and exercise stress.

Nixon, J. V.↗

NASA NTRS2008

Exercise Increases the Cardiovascular Stimulus Provided by Artificial Gravity

We investigated fluid shifts and regulatory responses to variations of posture, exercise, Gz level and radius of rotation in subjects riding NASA Ames 20G centrifuge. Results are from 4 protocols that address radius and exercise effects only. Protocol A: After 10 min supine control, 12 healthy men (35 plus or minus 9 yr, 82.8 plus or minus 7.9 kg) were exposed to rotational 1 Gz (2.5 m radius) for 2 min followed by 20 min alternating between 1 and 1.25 Gz. Blood samples were taken pre and post spin. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 8.3 m. Protocol D: Same as B but at 8.3 m. The 8 subjects who completed all protocols, increased heart rate (HR) from control, on average, by: A: 5, B: 39, C: 11, D: 44 bpm. For thoracic fluid volume, (bioimpedance), the 8 subjects changed from control, on average: A: -394, B: -548, C: -537, D: -708 mL. For thigh fluid volume, changes from control, on average, were: A: -137, B: 129, C: -75, D: 159 mL. Hematocrit changes from control were: A: 2.3, B: 3.5, C: 2.3, D: 4.3 %. Radius effects were mild and included greater loss of fluid from the thorax, less fluid loss from the thigh and increased heart rate at the longer radius. Pre-acceleration exercise effects were more dramatic and included additional loss of fluid from the chest, increased fluid volume of the thigh, increased hematocrit and greater heart rate increases. We propose that short bouts of intense exercise can be used to magnify the cardiovascular stress delivered by artificial gravity (AG) training and the combination of AG with exercise training can be fine-tuned to preserve orthostatic tolerance of astronauts during spaceflight.

Howarth, M. S.↗

NASA NTRS2008

Thoracic Impedance as a Potential Indicator of Gz-induced Presyncope

We investigated fluid shifts and regulatory responses to variations of posture, exercise, Gz level and radius of rotation in subjects riding NASA Ames 20G centrifuge. Results are from 4 protocols that address radius and exercise effects only. Protocol A: After 10 min supine control, 12 healthy men (35 9 yr, 82.8 7.9 kg) were exposed to rotational 1 Gz (2.5 m radius) for 2 min followed by 20 min alternating between 1 and 1.25 Gz. Blood samples were taken pre and post spin. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 8.3 m. Protocol D: Same as B but at 8.3 m. The 8 subjects who completed all protocols, increased heart rate (HR) from control by: A: 5, B: 39, C: 11, D: 44 bpm; and the 4 who did not: A: 6, B: 35, C: 20, D: 50 bpm. For thoracic fluid volume, (bioimpedance), the 8 subjects changed from control: A: -394, B: -548, C: -537, D: -708 mL; and the 4: A: -516, B: -652, C: -583, D: -1263 mL. The 4 subjects lost more thoracic fluid volume than the 8, especially in protocol D. A slightly greater increase in HR for the 4 compared to the 8 was not adequate to maintain cardiac output during D. Our data support the concept that thoracic impedance can detect inability to return adequate fluid to the heart, thereby predicting presyncope.

Howarth, M. S.↗

NASA NTRS2011

Computational Models of the Eye and their Applications in Long Duration Space Flight

Astronauts are exposed to cephalad fluid shift, increased carbon dioxide levels and other environmental factors during space flight. As a result of these conditions, it is believed that they are at risk of developing increased intracranial pressure (ICP) and intraocular pressure (IOP), which in turn may cause papilledema and other disorders of the eye that can lead to temporary or permanent changes in vision. However, the mechanisms behind this risk are not fully understood. Ground analog and flight studies pose challenges because there are limited non-invasive methods that can be used to study the eye and intracranial space. Therefore it is proposed that computational models can be applied to help address this gap by providing a low cost method for studying the effects of IOP, ICP and various properties of the eye on these diseases. The information presented by the authors provides a summary of several models found in literature that could potentially be augmented and applied to inform research. Specifically, finite element models of the optic nerve head, sclera and other structures of the eye can be readily adapted as potential building blocks. These models may also be integrated with a brain/cerebrospinal fluid (CSF) model which will take into account the interaction between the CSF fluid and its pressure on the optic nerve. This integration can enable the study of the effects of microgravity on the interaction between the vasculature system and CSF system and can determine the effects of these changes on the optic nerve, and in turn the eye. Ultimately, it can help pinpoint the influences of long-term exposure to microgravity on vision and inform the future research into countermeasure development. In addition to spaceflight, these models can provide deeper understanding of the mechanisms of glaucoma, papilledema and other eye disorders observed in terrestrial conditions.

Chen, Richard↗

NASA NTRS1998

Intracranial pressure dynamics during simulated microgravity using a new noninvasive ultrasonic technique

It is believed that intracranial pressure (ICP) may be elevated in microgravity because a fluid shift toward the head occurs due to loss of gravitational blood pressures. Elevated ICP may contribute to space adaptation syndrome, because as widely observed in clinical settings, elevated ICP causes headache, nausea, and projectile vomiting, which are similar to symptoms of space adaptation syndrome. However, the hypothesis that ICP is altered in microgravity is difficult to test because of the invasiveness of currently-available techniques. We have developed a new ultrasonic technique, which allows us to record ICP waveforms noninvasively. The present study was designed to understand postural effects on ICP and assess the feasibility of our new device in future flight experiments.

NASA Center ARC↗

NASA NTRS2001

Acoustic Issues in Human Spaceflight

NASA is concerned about acute effect of sound on crew performance on International Space Station (ISS), and is developing strategies to assess and reduce acute, chronic, and delayed effects of sound. High noise levels can cause headaches, irritation, fatigue, impaired sleep, headache, and tinnitus and have resulted in an inability to hear alarms. Speech intelligibility may be more impaired for crew understanding non-native language in a noisy environment. No hearing loss occurred, but significant effects on crew performance and communication occurred. Permanent Threshold Shifts (PTS) have not been observed in the US shuttle program. Russian specification for noise in spacecraft is 60 dBA (awake) and 50 dBA (asleep) while the U.S. noise specification on ISS is NC 50 (awake) and NC 40 (asleep) with a 85 dBA hazard limit. Background noise levels of ISS modules have measured 56-69 dBA. Treadmill exercise operations measure 77 dBA. Alarms are required to be 20 dBA above ambient. Hearing protection is recommended when noise exceeds 60 dB 24 hour Leq. Countermeasures include hearing protection and design/ engineering controls. Advanced composite materials with excellent low frequency attenuation properties could be applied as a barrier protection around noisy equipment, or used on personal protective equipment worn by the crew. Hearing protection countermeasures include foam ear inserts, passive muff headsets, and active noise reduction headsets. Oto-acoustic emissions (OAE) could be used to monitor effectiveness of hearing protection countermeasures and tailor hearing protection countermeasures to individual crewmembers. Micro-gravity, vibration, toxic fumes, air quality/composition, stress, temperature, physical exertion or some combination of the above factors may have interacted with moderate long-term noise exposure to cause significant hearing loss. Longitudinal studies will need to address what co-morbidity factors, such as radiation, toxicology, microgravity effects (fluid shift), aging, are involved with hearing loss.

Clark, Jonathan B.↗

NASA NTRS2000

Antiorthostatic suspension for 14 days does not diminish the oxidative response of neutrophils in mice

The effects of long-term spaceflight on inflammatory responses have not been well-studied in either humans or animals. It is thus important to determine if the functions of immune and inflammatory cells are altered in models of spaceflight. One such animal model is antiorthostatic suspension (AOS), in which the experimental animal is subjected to a head-down tilt that mimics both the stress and the cephalad fluid shift experienced in spaceflight. A previous study reported that the peritoneal neutrophils from mice experiencing AOS generated less superoxide than unsuspended controls. We expanded on this study using several different stimuli and measuring the oxidative response of murine neutrophils in a variety of ways. These responses included the rate, lag period, and dose/response characteristics for superoxide generation, FACS analysis with dihydrodichlorofluorescein as a substrate, and a chemiluminescence response with luminol as a substrate. We also examined phagocytosis of three different microorganisms. While some effects of orthostatic suspension (attributable to the stress of the apparatus) were observed, no clear effects of AOS on oxidative function of the peritoneal neutrophils were seen.

NASA Discipline Regulatory Physiology↗

NASA NTRS2016

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗

NASA NTRS2016

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

biomechanics↗

NASA NTRS2009

Acute Hemodynamic Effects of the Braslet-M Device on the International Space Station

The Braslet-M occlusion device is prescribed for cosmonauts as a countermeasure for early phases of spaceflight to temporarily alleviate symptoms associated with the cephalad fluid shift. Using a multipurpose ultrasound (US) device onboard, we assessed the acute hemodynamic effects of the Bracelet-M device on a long duration International Space Station (ISS) crewmember. Methods A combination of just-in-time training and real-time remote expert assistance was used to conduct the imaging procedures. An HDI-5000 imager (Philips, Bothell, WA) was used, provided by the ISS Human Research Facility. Superficial femoral artery (SFA), femoral vein (FV) flow spectra were obtained at mid-thigh level. Left ventricle was imaged through the apical 4-chamber view, with Color M-Mode to measure propagation velocity (V (p)). After 10 minutes of Bracelet-M use, data collection was repeated. All data were transmitted in DICOM format to ground for analysis. Results With Braslet-M, cardiac V(p) slope decreased (56ms to 42ms). A stagnation signature in the FV was seen suggesting impeded flow (rouleaux formation, too-low-to-measure velocity, and increase in diameter). Quadri-phasic flow in SFA was seen both before and after Braslet-M application. Velocities in the SFA decreased with Braslet-M (65cm/sec to 52cm/sec) and so did the time velocity integrals (16.97 to 12.4); the flow pattern spoke of resistivity increase in the vascular bed. Conclusion In the long duration ISS crewmember we observed effects of lower extremity venous occlusion through both central and peripheral indicators. A part of circulating volume transferred to peripheral potential vascular space. Impediment to venous outflow was demonstrated objectively, with a commensurate change in the flow pattern of the main feeding artery. Central volume reduction caused lower V(p). Additional studies are warranted to determine the time course of the changes and the dynamics in interstitial fluid sequestration, as well as the safe levels and duration of the compression forces.

Hamilton, Douglas R.↗