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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.↗

NASA NTRS2016

Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as ICP was elevated (Fig. 2). In particular, c. 48 of simulations in the elevated ICP condition showed peak strains in the optic nerve that exceeded the strains expected on earth. Such extreme strains are likely important, since they represent a larger signal for mechano-responsive resident cells [2]. The models predicted little to no anterior motion of the prelaminar neural tissue (optic nerve swelling, or papilledema, secondary to axoplasmic stasis), typically seen with elevated ICP. Specialized FE models to capture axoplasmic stasis would be required to study papilledema. These results suggest that the most notable effect of elevated ICP may occur via direct optic nerve loading, rather than through connective tissue deformation. These FE models can inform the design of future studies designed to bridge the gap between biomechanics and pathophysiological function in VIIP.

biomechanics↗

NASA NTRS1994

US experiment flown on the Soviet biosatellite Cosmos 1667

Two male young-adult rhesus monkeys were flown on the Soviet Biosatellite Cosmos 1667 for seven days from July 10-17, 1985. Both animals were instrumented to record neurophysiological parameters. One animal, Gordyy, was additionally instrumented to record cardiovascular changes. Space capsule and environmental parameters were very similar to those of previous missions. On Cosmos 1514, which flew for five days in 1983, one animal was fitted with a left carotid artery cuff to measure blood pressure and flow velocity. An additional feature of Cosmos 1667 was a postflight control study using the flight animal. Intermittent postural tilt tests were also conducted before and after spaceflight and synchronous control studies, to simulate the fluid shifts associated with spaceflight. The experiment results support the conclusion derived from Cosmos 1514 that significant cardiovascular changes occur with spaceflight. The changes most clearly seen were rapid initial decreases in heart rate and further decreases with continued exposure to microgravity. The triggering mechanism appeared to be a headward shift in blood and tissue fluid volume which, in turn, triggered adaptive cardiovascular changes. Adaptive changes took place rapidly and began to stabilize after the first two days of flight. However, these changes did not plateau in the animal by the last day of the mission.

Hines, John W.↗

NASA NTRS1997

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Clinical Trial↗

NASA NTRS1978

A review of the consequences of fluid and electrolyte shifts in weightlessness

This review describes the renal-endocrine mechanisms related to the early losses of fluid-electrolytes from the body during weightlessness as well as their contribution to longer term adaptation of fluid-electrolyte balance. The hypotheses presented were generated by a systematic analysis of body fluid and renal dynamics observed under conditions of actual and simulated spaceflight. These have increased our understanding of the effects of acute headward fluid shifts on renal excretion, the factors promoting excess sodium excretion and the regulation of extracellular fluid composition.

Leach, C. S.↗

NASA NTRS1979

A review of the consequences of fluid and electrolyte shifts in weightlessness

Review↗

NASA NTRS1995

Alterations in glomerular and tubular dynamics at 1 and 14 days simulated microgravity and after acute return to orthostasis

Head-down tilt (HDT) is utilized to simulate microgravity and produces a cephalad fluid shift, which results in alterations in fluid and electrolyte balance. These changes in volume homeostasis are due, in part, to alterations in multiple volume control mechanisms in which renal function is a major participant. We have previously demonstrated that glomerular filtration rate increases early in HDT and eventually returns to values not different from non-tilt measurements. This early increase in glomerular filtration rate was also demonstrated during days 2 and 8 of the SLS-1 mission. However, urine flow and electrolyte excretion does not parallel the alternations in glomerular filtration rate and the site of this change in nephron fluid reabsorption pattern has not been previously examined. Through determination of the location of alterations in tubular fluid reabsorption within the nephron, a more detailed hypothesis can be forwarded as to which specific neuro-humoral agents participating in control or renal function in microgravity conditions. the importance of this type of examination is that measurements in circulating neuro-humoral agents and urinary excretion patterns alone are not accurate predictors of how renal functional response may alter to head-down tilt or other models of simulated weightlessness. To examine this issue, renal micropuncture techniques were utilized in Munich-Wistar rats submitted 24 hour and 14 day head-down tilt, measuring all the determinants of glomerular ultrafiltration and obtaining data regarding segmental tubular fluid reabsorption. Following these measurements, the rats were returned to an orthostatic position and after 60 minutes, the measurements were repeated.

Tucker, Bryan J.↗

NASA NTRS1994

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Review↗

NASA NTRS1979

Space motion sickness

Research on the etiology, prediction, treatment and prevention of space motion sickness, designed to minimize the impact of this syndrome which was experienced frequently and with severity by individuals on the Skylab missions, on Space Shuttle crews is reviewed. Theories of the cause of space motion sickness currently under investigation by NASA include sensory conflict, which argues that motion sickness symptoms result from a mismatch between the total pattern of information from the spatial senses and that stored from previous experiences, and fluid shift, based upon the redistribution of bodily fluids that occurs upon continued exposure to weightlessness. Attempts are underway to correlate space motion sickness susceptibility to different provocative environments, vestibular and nonvestibular responses, and the rate of acquisition and length of retention of sensory adaptation. Space motion sickness countermeasures under investigation include various drug combinations, of which the equal combination of promethazine and ephedrine has been found to be as effective as the scopolomine and dexedrine combination, and vestibular adaptation and biofeedback training and autogenic therapy.

Homick, J. L.↗

NASA NTRS1994

Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

Posture↗

NASA NTRS2016

Characterization of the Biomechanical Behavior of the Optic Nerve Sheath

A major priority in current space medicine research is to characterize the mechanisms in Visual Impairment and Intracranial Pressure (VIIP) syndrome, a group of ophthalmic changes that occur in some astronauts following long-duration spaceflight [1]. It is hypothesized that microgravity-induced cephalad fluid shifts lead to increases in intracranial pressure (ICP), which drives maladaptive remodeling of the optic nerve sheath (ONS). In this study, we investigated the effects of mechanical loading on the porcine ONS to better understand the mechanical response of the ONS to increased ICP.

fluid shift (biological)↗

NASA NTRS1987

Results of the Life Sciences DSOs Conducted Aboard the Space Shuttle 1981-1986

Results are presented for a number of life sciences investigations sponsored by the Space Biomedical Research Institute at the NASA Lyndon B. Johnson Space Center and conducted as Detailed Supplementary Objectives (DSOs) on Space Shuttle flights between 1981 and 1986. An introduction and a description of the DSO program are followed by summary reports on the investigations. Reports are grouped into the following disciplines: Biochemistry and Pharmacology, Cardiovascular Effects and Fluid Shifts, Equipment Testing and Experiment Verification, Microbiology, Space Motion Sickness, and Vision. In the appendix, the status of every medical/life science DSO is presented in graphical form, which enables the flight history, the number of subjects tested, and the experiment results to be reviewed at a glance.

Vestibular Research↗

NASA NTRS2017

The Impact of Ocular Pressures, Material Properties and Geometry on Optic Nerve Head Deformation

Alteration in intracranial pressure (ICP) has been associated with various diseases that cause visual impairment, including glaucoma, idiopathic intracranial hypertension and Visual Impairment and Intracranial Pressure (VIIP) syndrome. However, how changes in ICP lead to vision loss is unclear, although it is hypothesized to involve deformations of the tissues in the optic nerve head (ONH). Recently, understanding the effect of ICP alterations on ocular tissues has become a major concern for NASA, where 42 of astronauts that partake in long duration space missions suffer from VIIP syndrome. Astronauts with VIIP syndrome suffer from visual impairment and changes in ocular anatomy that persist after returning to earth (1). It is hypothesized that the cephalad fluid shift that occurs upon entering microgravity increases ICP, which leads to an altered biomechanical environment in the posterior globe and optic nerve sheath, and subsequently VIIP syndrome. Our goal was to develop a finite element (FE) model to simulate the acute effects of elevated ICP on the posterior eye. Here, we simulated how inter-individual differences affect the deformation of ONH tissues. Further, we examined how several different geometries influenced deformations when exposed to elevated ICP.

mathematical models↗

NASA NTRS2015

Finite Element Modeling Techniques for Analysis of VIIP

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP.

eye (anatomy)↗

NASA NTRS2015

Finite Element Modeling of the Posterior Eye in Microgravity

Microgravity experienced during spaceflight affects astronauts in various ways, including weakened muscles and loss of bone density. Recently, visual impairment and intracranial pressure (VIIP) syndrome has become a major concern for space missions lasting longer than 30 days. Astronauts suffering from VIIP syndrome have changes in ocular anatomical and visual impairment that persist after returning to earth. It is hypothesized that a cephalad fluid shift in microgravity may increase the intracranial pressure (ICP), which leads to an altered biomechanical environment of the posterior globe and optic nerve sheath (ONS).Currently, there is a lack of knowledge of how elevated ICP may lead to vision impairment and connective tissue changes in VIIP. Our goal was to develop a finite element model to simulate the acute effects of elevated ICP on the posterior eye and optic nerve sheath. We used a finite element (FE) analysis approach to understand the response of the lamina cribrosa and optic nerve to the elevations in ICP thought to occur in microgravity and to identify which tissue components have the greatest impact on strain experienced by optic nerve head tissues.

intraocular pressure↗

NASA NTRS1984

Physiology of Fluid and Electrolyte Responses During Inactivity: Water Immersion and Bed Rest

This manuscript emphasizes the physiology of fluid-electrolyte-hormonal responses during the prolonged inactivity of bed rest and water immersion. An understanding of the total mechanism of adaptation (deconditioning) should provide more insight into the conditioning process. Findings that need to be confirmed during bed rest and immersion are: (1) the volume and tissues of origin of fluid shifted to the thorax and head; (2) interstitial fluid pressure changes in muscle and subcutaneous tissue, particularly during immersion; and (3) the composition of the incoming presumably interstitial fluid that contributes to the early hypervolemia. Better resolution of the time course and source of the diuretic fluid is needed. Important data will be forthcoming when hypotheses are tested involving the probable action of the emerging diuretic and natriuretic hormones, between themselves and among vasopressin and aldosterone, on diuresis and blood pressure control.

Greenleaf, John E.↗

NASA NTRS2010

Dose-Response Evaluation of Braslet-M Occlusion Cuffs

Introduction: Braslet-M is a set of special elasticized thigh cuffs used by the Russian space agency to reduce the effects of the head-ward fluid shift during early adaptation to microgravity by sequestering fluid in the lower extremities. Currently, no imaging modalities are used in the calibration of the device, and the pressure required to produce a predictable physiological response is unknown. This investigation intends to relate the pressure exerted by the cuffs to the extent of fluid redistribution and commensurate physiological effects. Materials and Methods: Ten healthy subjects with standardized fluid intake participated in the study. Data collection included femoral and internal jugular vein imaging in two orthogonal planes, pulsed Doppler of cervical and femoral vessels and middle cerebral artery, optic nerve imaging, and echocardiography. Braslet-M cuff pressure was monitored at the skin interface using pre-calibrated pressure sensors. Using 6 and 30 head-down tilt in two separate sessions, the effect of Braslet-M was assessed while incrementally tightening the cuffs. Cuffs were then simultaneously released to document the resulting hemodynamic change. Results: Preliminary analysis shows correlation between physical pressure exerted by the Braslet-M device and several parameters such as jugular and femoral vein cross-sections, resistivity of the lower extremity vascular bed, and others. A number of parameters reflect blood redistribution and will be used to determine the therapeutic range of the device and to prevent unsafe application. Conclusion: Braslet-M exerts a physical effect that can be measured and correlated with many changes in central and peripheral hemodynamics. Analysis of the full data set will be required to make definitive recommendations regarding the range of safe therapeutic application. Objective data and subjective responses suggest that a safer and equally effective use of Braslet can be achieved when compared with the current non-imaging calibration techniques.

Ebert, Douglas↗

NASA NTRS1986

Fluid and protein shifts after postural changes in humans

The effects of head-up, one-step, slow-graded, and rapid-graded tilt positions on blood density (BD), plasma density (PD), and erythrocyte density (ED) in male and female subjects are evaluated using a mass density detection method. The preparation of the samples and procedures for density and hematocrit measurements are described. The formula for calculating the density and volume of fluid shifted between intravascular and extravascular compartments is derived. The data reveal that ED does not change with varying tilt positions; however, PD and BD increase linearly with increasing angles of tilt, thereby resembling the time course of hemodilution and hemoconcentration.

Hinghofer-Szalkay, H.↗