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Changes in left ventricular function as determined by the multi-wire gamma camera at near presyncopal levels of lower body negative pressure

At presyncopal levels of lower body negative pressure (LBNP), we have frequently observed electrocardiographic responses that may be due to changes in cardiac position and/or shape, but could be indicative of altered myocardial function. To further investigate this, we evaluated cardiac function using a nuclear imaging technique in 21 healthy subjects (17 men and 4 women) after 30 minutes of supine rest and near the end of a presyncopal-limited LBNP exposure (LBNP averaged 65 plus or minus 3 mmHg at injection). Cardiac first pass images were obtained with a Multi-Wire Gamma Camera following an intravenous bolus injection of 30-50 millicurries of Tantalum-178. Manual blood pressures and electrocardiograms were obtained throughout the 3 minute graded LBNP protocol. Between rest and injection during LBNP, heart rate increased (P less than 0.01) from 67 plus or minus 3 beats per minute to 99 plus or minus beats per minute, systolic blood pressure decreased (P less than 0.01) from 110 plus or minus 3 mmHg to 107 plus or minus 3 mmHg and left ventricular ejection fraction (EF) decreased (P less than 0.01) from 0.57 plus or minus 0.02 to 0.48 plus or minus 0.02. During LBNP, ST segment depression of at least 0.5 mm occurred in 7 subjects. Subjects with ST depression had greater reductions (P = 0.05) in EF than subjects without ST depression (0.15 plus or minus 0.07 versus 0.005 plus or minus 0.03), but also tolerated greater levels (P less than 0.05) of negative pressure (88 plus or minus mmHg versus 69 plus or minus 5 mmHg). There was a significant relationship between presyncopal LBNP level and EF (R(exp 2) = 0.50, P less than 0.05). Our findings suggest there may be a decrease in systolic myocardial function at high levels of LBNP.

Pintner, R.↗

Effects of body orientation and rotation axis on pitch visual-vestibular interaction

Spatial transformations of the vestibular-optokinetic system must account for changes in head position with respect to gravity in order to produce compensatory oculomotor responses. The purpose of this experiment was to study the influence of gravity on the vestibulo-ocular reflex (VOR) in darkness and on visual-vestibular interaction in the pitch plane in human subjects using two different comparisons: (1) Earth-horizontal axis (EHA) rotation about an upright versus a supine body orientation, and (2) Earth-horizontal versus Earth-vertical (EVA) rotation axes. Visual-vestibular responses (VVR) were evaluated by measuring the slow phase velocity of nystagmus induced during sinusoidal motion of the body in the pitch plane (at 0.2 Hz and 0.8 Hz) combined with a constant-velocity vertical optokinetic stimulation (at +/- 36 degrees/s). The results showed no significant effect on the gain or phase of the VOR in darkness or on the VVR responses at 0.8 Hz between EHA upright and EHA supine body orientations. However, there was a downward shift in the VOR bias in darkness in the supine orientation. There were systematic changes in VOR and VVR between EHA and EVA for 0.2 Hz, including a reduced modulation gain, increased phase lead, and decreased bias during EVA rotation. The same trend was also observed at 0.8 Hz, but at a lesser extent, presumably due to the effects of eccentric rotation in our EVA condition and/or to the different canal input across frequencies. The change in the bias at 0.2 Hz between rotation in darkness and rotation with an optokinetic stimulus was greater than the optokinetic responses without rotation. During EHA, changes in head position relative to gravity preserve graviceptor input to the VVR regardless of body orientation. However, the modifications in VVR gain and phase when the rotation axis is aligned with gravity indicate that this graviceptive information is important for providing compensatory eye movements during visual-vestibular interaction in the pitch plane.

Non-NASA Center↗

Lumbar spine disc height and curvature responses to an axial load generated by a compression device compatible with magnetic resonance imaging

STUDY DESIGN: Axial load-dependent changes in the lumbar spine of supine healthy volunteers were examined using a compression device compatible with magnetic resonance imaging. OBJECTIVE: To test two hypotheses: Axial loading of 50% body weight from shoulder to feet in supine posture 1) simulates the upright lumbar spine alignment and 2) decreases disc height significantly. SUMMARY OF BACKGROUND DATA: Axial compression on the lumbar spine has significantly narrowed the lumbar dural sac in patients with sciatica, neurogenic claudication or both. METHODS: Using a device compatible with magnetic resonance imaging, the lumbar spine of eight young volunteers, ages 22 to 36 years, was axially compressed with a force equivalent to 50% of body weight, approximating the normal load on the lumbar spine in upright posture. Sagittal lumbar magnetic resonance imaging was performed to measure intervertebral angle and disc height before and during compression. RESULTS: Each intervertebral angle before and during compression was as follows: T12-L1 (-0.8 degrees +/- 2.5 degrees and -1.5 degrees +/- 2.6 degrees ), L1-L2 (0.7 degrees +/- 1.4 degrees and 3.3 degrees +/- 2.9 degrees ), L2-L3 (4.7 degrees +/- 3.5 degrees and 7.3 degrees +/- 6 degrees ), L3-L4 (7.9 degrees +/- 2.4 degrees and 11.1 degrees +/- 4.6 degrees ), L4-L5 (14.3 degrees +/- 3.3 degrees and 14.9 degrees +/- 1.7 degrees ), L5-S1 (25.8 degrees +/- 5.2 degrees and 20.8 degrees +/- 6 degrees ), and L1-S1 (53.4 degrees +/- 11.9 degrees and 57.3 degrees +/- 16.7 degrees ). Negative values reflect kyphosis, and positive values reflect lordosis. A significant difference between values before and during compression was obtained at L3-L4 and L5-S1. There was a significant decrease in disc height only at L4-L5 during compression. CONCLUSIONS: The axial force of 50% body weight in supine posture simulates the upright lumbar spine morphologically. No change in intervertebral angle occurred at L4-L5. However, disc height at L4-L5 decreased significantly during compression.

Non-NASA Center↗

Mechanisms of Orthostatic Tolerance Improvement Following Artificial Gravity Exposure Differ Between Men and Women

We recently determined that a short exposure to artificial gravity (AG) improved the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned subjects. We now seek to determine the mechanisms of that improvement in these hypovolemic men and women. Methods. We determined the orthostatic tolerance limit (OTL) of 9 men and 8 women following a 90 min exposure to AG compared to 90 min of head down bed rest (HDBR). In both cases (21 days apart), subjects were made hypovolemic (low salt diet plus 20 mg intravenous furosemide). Orthostatic tolerance was determined from a combination of head up tilt and increasing lower body negative pressure until presyncope. Mean values and correlations with OTL were determined for heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (Finometer), cerebral artery blood velocity (DWL), partial pressure of carbon dioxide (Novametrics) and body segmental impedance (UFI THRIM) were measured during supine baseline, during OTL to presyncope and during supine recovery Results. Orthostatic tolerance of these hypovolemic subjects was significantly greater on the day of AG exposure than on the HDBR day. Regression of OTL on these variables identified significant relationships on the HDBR day that were not evident on the AG day: resting TPR correlated positively while resting cerebral flow correlated negatively with OTL. On both days, women's resting stroke volume correlated positively with orthostatic tolerance. Higher group mean values of stroke volume and cerebral artery flow and lower values of blood pressure, peripheral vascular and cerebrovascular resistance both at control and during OTL testing were observed on the AG day. Even though regression of OTL on resting stroke volume was significant only in women, presyncopal stroke volume reached the same level on each day of study for both men and women while the OTL test lasted 30% longer in men and 22% longer in women. Cerebral artery flow appeared to follow stroke volume and absolute values of cerebral flow did not correlate with the development of presyncope. Women responded to AG exposure with elevated cerebral flow at resting control and throughout the OTL test, implying a loss of autoregulation in deconditioned (hypovolemic) women following AG exposure. Conclusions. Before countermeasures to space flight cardiovascular deconditioning are established, gender differences in cardiovascular responses to orthostatic stress, in general, and to orthostatic stress following exposure to artificial gravity, in particular, need to be determined. Since, in both men and women, a single, acute bout of AG exposure improved orthostatic tolerance, the feasibility of short exposures to AG during longer spaceflights or prior to entry into a gravity (Earth or Mars) environment, should be explored. Given the known beneficial effects of AG on other organ systems, the present study indicates that the positive effects of AG on cardiac stroke volume make AG a likely candidate for maintaining cardiovascular conditioning.

Evans, J. M.↗

Intracranial Effects of Intermittent Lower Body Negative Pressure with Head Down Tilt Bed Rest: Comparison to Upright Posture

INTRODUCTION Spaceflight-associated neuro-ocular syndrome (SANS) affects a majority of astronauts during long-duration spaceflight. SANS is hypothesized to result from an unrelenting headward fluid shift that occurs in the microgravity environment. Altered intracranial structure and physiology documented in spaceflight and head-down tilt (HDT) experiments(1, 2) are also theorized to be related to chronic headward fluid shift and thereby can provide an independent quantitative assessment related to this mechanism. As a potential countermeasure, lower body negative pressure (LBNP) applied in the supine posture has shown efficacy in reducing headward fluid shift(3). However, it remains unknown if intermittent LBNP simulating daily upright posture fluid redistribution can mitigate SANS and intracranial changes associated with long-duration spaceflight. The goal of this study was to quantify the effects of daily application of LBNP or daily exposure to the upright posture on intracranial structure and physiology during long-term HDT in order to evaluate the potential efficacy of LBNP as a countermeasure to SANS. METHODS 22 healthy volunteers (11 men; 11 women; mean age = 35 years (SD=9.2)(age range = 24 to 52 years); mean BMI = 24.0 kg/m2 (SD=2.8)) completed an MRI study performed at the German Aerospace Facility in Cologne, Germany. Strict six-degree head-down tilt (HDT) bedrest was used as a spaceflight analog to induce a continuous headward fluid shift for 30 days. The subjects were divided equally into two groups of interventions: 1) LBNP for 3-hour sessions twice daily and 2) seated position for 3-hour sessions twice daily. Interventions were divided into morning and afternoon sessions for both groups. The LBNP intervention was maintained at 25 mmHg  2 mmHg. Pulse-gated MRI phase-contrast flow imaging was used to quantify cerebral artery stroke volume (CASV) and peak-to-peak cerebral spinal fluid (CSF) velocity (CSFVp-p) within the cerebral aqueduct. A 3D T1-MPRAGE sequence was used to quantify volumetric changes of the brain and intracranial CSF spaces using MRI Cloud software. MRI acquisitions were obtained at baseline (BDC, supine posture), 15 days into HDT (HDT15), 29 days into HDT (HDT29), and 12 days after recovery (R12, supine posture). The data were analyzed by a mixed model, which included intervention, time (four nominal levels BDC, HDT15, HDT29, R12), and intervention-time interaction as the fixed effects and included subject as a random effect. RESULTS Compared to BDC there was no statistically significant difference in CASV and CSFVp-p during HDT except for CASV at HDT29 (seated group) where there was a 1.7 mL (12%) decrease (P<0.01). Compared to BDC there was a statistically significant increase in intracranial volume (ICV; ICV = white matter + gray matter + CSF) for both interventions at HDT15 (Δ13 mL, 0.9 % (LBNP group); Δ15 mL, 1.0%, (seated group)) and HDT29 (Δ19 mL, 1.2%, (LBNP group); Δ23 mL, 1.5%) (seated group)) (All Ps<.001). Compared to baseline, lateral ventricular volume increased at HDT15 (Δ0.9 mL, 5.5%) and HDT29 (Δ1.8 mL, 10%)) for LBNP only (P=.001 for each). During HDT, white matter volume remained stable compared to baseline for both interventions. There were no significant intervention effects in the overall response to HDT (All Ps >.2). CONCLUSION LBNP had a similar response to the seated posture during 29 days of HDT. Although there was an increase in ICV and lateral ventricular volume with HDT there was no change in intracranial physiological parameters with LBNP suggesting an overall diminished response to the long-term effects of HDT. The lack of any significant increase in white matter volume during HDT with LBNP suggests maintenance of cerebral interstitial fluid transport. Final conclusions are pending the data collection for the control group (no intervention) which will be completed in 2023.

Larry A Kramer↗

Accuracy of saccades to remembered targets as a function of body orientation in space

A vertical asymmetry in memory-guided saccadic eye movements has been previously demonstrated in humans and in rhesus monkeys. In the upright orientation, saccades generally land several degrees above the target. The origin of this asymmetry has remained unknown. In this study, we investigated whether the asymmetry in memory saccades is dependent on body orientation in space. Thus animals performed memory saccades in four different body orientations: upright, left-side-down (LSD), right-side-down (RSD), and supine. Data in all three rhesus monkeys confirm previous observations regarding a significant upward vertical asymmetry. Saccade errors made from LSD and RSD postures were partitioned into components made along the axis of gravity and along the vertical body axis. Up/down asymmetry persisted only in body coordinates but not in gravity coordinates. However, this asymmetry was generally reduced in tilted positions. Therefore the upward bias seen in memory saccades is egocentric although orientation in space might play a modulatory role.

NASA Discipline Neuroscience↗

Upper Body Venous Compliance Exceeds Lower Body Venous Compliance in Humans

Human venous compliance hypothetically decreases from upper to lower body as a mechanism for maintenance of the hydrostatic indifference level 'headward' in the body, near the heart. This maintains cardiac filling pressure, and thus cardiac output and cerebral perfusion, during orthostasis. This project entailed four steps. First, acute whole-body tilting was employed to alter human calf and neck venous volumes. Subjects were tilted on a tilt table equipped with a footplate as follows: 90 deg, 53 deg, 30 deg, 12 deg, O deg, -6 deg, -12 deg, -6 deg, O deg, 12 deg, 30 deg, 53 deg, and 90 deg. Tilt angles were held for 30 sec each, with 10 sec transitions between angles. Neck volume increased and calf volume decreased during head-down tilting, and the opposite occurred during head-up tilt. Second, I sought to cross-validate Katkov and Chestukhin's (1980) measurements of human leg and neck venous pressures during whole-body tilting, so that those data could be used with volume data from the present study to calculate calf and neck venous compliance (compliance = (Delta)volume/(Delta)pressure). Direct measurements of venous pressures during postural chances and whole-body tilting confirmed that the local changes in venous pressures seen by Katkov and Chestukhin (1980) are valid. The present data also confirmed that gravitational changes in calf venous pressure substantially exceed those changes in upper body venous pressure. Third, the volume and pressure data above were used to find that human neck venous compliance exceeds calf venous compliance by a factor of 6, thereby upholding the primary hypothesis. Also, calf and neck venous compliance correlated significantly with each other (r(exp 2) = 0.56). Fourth, I wished to determine whether human calf muscle activation during head-up tilt reduces calf venous compliance. Findings from tilting and from supine assessments of relaxed calf venous compliance were similar, indicating that tilt-induced muscle activation is relatively unimportant. Low calf venous compliance probably results from stiffer venous, skeletal muscle, and connective tissues, and better-developed local and central neural controls of venous distensibility. This research establishes that upper-to-lower body reduction of venous compliance can explain headward positioning of the hydrostatic indifference level in humans.

Watenpaugh, Donald E.↗

Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.

biomechanics↗

Vivid Motor Imagery as an Adaptation Method for Head Turns on a Short-Arm Centrifuge

Artificial gravity (AG) has been proposed as a potential countermeasure to the debilitating physiological effects of long duration space flight. The most economical means of implementing AG may be through the use of a short-radius (2m or less) centrifuge. For such a device to produce gravitational forces comparable to those on earth requires rotation rates in excess of 20 revolutions per minute (rpm). Head turns made out of the plane of rotation at these rates, as may be necessary if exercise is combined with AG, result in cross-coupled stimuli (CCS) that cause adverse side effects including motion sickness, illusory sensations of motion, and inappropriate eye movements. Recent studies indicate that people can adapt to CCS and reduce these side effects by making multiple head turns during centrifuge sessions conducted over consecutive days. However, about 25% of the volunteers for these studies have difficulty tolerating the CCS adaptation paradigm and often drop out due to motion sickness symptoms. The goal of this investigation was to determine whether vivid motor imagery could be used as a pseudostimulus for adapting subjects to this unique environment. Twenty four healthy human subjects (14 males, 10 females), ranging in age from 21 to 48 years (mean 33, sd 7 years) took part in this study. The experimental stimuli were produced using the NASA JSC short-arm centrifuge (SAC). Subjects were oriented supinely on this device with the nose pointed toward the ceiling and head centered on the axis of rotation. Thus, centrifuge rotation was in the body roll plane. After ramp-up the SAC rotated clockwise at a constant rate of 23 rpm, producing a centrifugal force of approximately 1 g at the feet. Semicircular canal CCS were produced by having subjects make yaw head turns from the nose up (NU) position to the right ear down (RED) position and from RED to NU. Each head turn was completed in about one second, and a 30 second recovery period separated consecutive head movements. Participants were randomly assigned to one of three groups (n=8 per group): physical adapters (PA), mental adapters (MA), or a control group (CG). Each subject participated in a one hour test session on each of three consecutive days. Each test session consisted of an initial (preadaptation) period during which the subject performed six CCS maneuvers in the dark, followed by an adaptation period with internal lighting on the centrifuge, and a final (postadaptation) period during which six more CCS maneuvers were performed in the dark. For the PA group, the adaptation period consisted of performing 30 additional CCS maneuvers in the light. For the MA and CG group the centrifuge was ramped down to 0 rpm after the pre-adaptation period and ramped back up to 23 rpm before the post-adaptation period. For the both of these groups, the adaptation period consisted of making 30 CCS maneuvers in the light with the centrifuge stationary (so no cross-coupling occurred). MA group subjects were instructed to vividly imagine the provocative sensations produced by the preadaptation CCS maneuvers in terms of magnitude, duration, and direction of illusory body tilt, as well as any accompanying levels of motion sickness. CG group subjects were asked to answer low imagery content questions (trivial pursuit) during each adaptation period head turn. During the 30 second recovery following each head turn, psychophysical data were collected including self reports of motion sickness, magnitude and direction estimates of illusory body tilt, and the overall duration of these sensations. A multilevel mixed effects linear regression analysis performed on all response variables indicated that all three groups experienced some psychophysical adaptation across the three test sessions. For illusory tilt magnitude, the PA group exhibited the most overall adaptation, followed by the MA group, and the CG group. The slopes of these adaptation trajectories by group over day were significantly diffent from one another. For the perceived duration of sensations, the CG group again exhibited the least amount of adaptation. However, the rates of adaptation of the PA and the MA groups were indistinguishable, suggesting that the imagined pseudostimulus appeared to be just as effective a means of adaptation as the actual stimulus. The MA group's rate of adaptation to motion sickness symptoms was also comparable to the PA group. The use of vivid motor imagery may be an effective method for adapting to the illusory sensations and motion sickness symptoms produced by cross-coupled stimuli. For space-based AG applications, this technique may prove quite useful in retaining astronauts considered highly susceptible to motion sickness as it reduces the number of actual CCS required to attain adaptation.

Newby, N. J.↗

Histopathology of the Chimpanzee Ear

Four female and two male chimpanzees were secured in various positions on a Daisy Decelerator and subjected to forces ranging from 54 to 180 G. It was found that forces in excess of 54 G may rupture the tympanic membranes and cause subepithelial hemorrhages in the middle ear. The majority of cases showed proteinaceous material, with or without cells in the petrous air spaces. When exposed to forces above 119 G, there was engorgement and often rupture of the pericarotid venous plexus. When supine, distortion of both superior and posterior semicircular canals was found. With forces in excess of 54 G, the cupulae of the cristae ampullaris were either elevated or destroyed. The hair processes were also often broken off. The otolithic membranes, especially of the maculae utriculi were also elevated or otherwise distorted and the saccule was often partially collapsed. In several instances, there was an overabundance of a proteinaceous substance in the lumina of the vestibular apparatus and in the cochlear ducts with their associated scalae. In half the cases, the cochlear duct was narrowed by the depression of the vestibular membrane. Although there seems to be considerable individual variation in ability to withstand these forces, neither age, sex nor weight appear to directly influence the results. The possible sources for the materials found both in the air cells and labyrinth are discussed.

ACCELERATION TOLERANCE↗

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

Smith, Scott M.↗

Fluid Redistribution and Heart Rate in Humans During Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure

Gravity creates blood pressure gradients which redistribute body fluids towards the feet. Positive G(z) centrifugation and lower body negative pressure (LBNP) have been proposed to simulate these and other effects of gravity during long-term existence in microgravity. We hypothesized that the magnitude of upper-to-lower body fluid redistribution would increase according to the following order: short-arm centrifugation (SAC), long-arm centrifugation (LAC), head-up tilt (HUT), and LBNP. To test this hypothesis, we employed strain gauge plethysmography of the neck, thigh and calf during HUT and supine SAC and LAC up to lG(z) at the feet, and during supine LBNP to 100 mm Hg. Supine 100 mm Hg LBNP generates footward force and produces transmural blood pressures in the foot approximately equal to 1 G(z) (90 deg) HUT. Heart rate was measured via cardiotachometry. Control measurements were made while supine. SAC and LAC elicited similar increases in thigh volume at 1 G(z) (2.3 +/- 0.4 and 2.1 +/- 0.1%, respectively; mean +/- se, n greater than or equal to 7). At 100 mm Hg LBNP, thigh volume increased (3.4 +/- 0.3%) significantly more than during l G(z) centrifugation (p less than 0.05). Surprisingly, due to a paradoxical 0.6% reduction of thigh volume between 0.8 and 1.0 G(z) HUT, thigh volume was increased only 0.6 +/- 0.3% at 1 G(z) HUT. The calf demonstrated similar, although less definitive, responses to the various gravitational stimuli. Neck volume tended to decrease less during HUT than during the other stimuli. Heart rate increased similarly during HUT (18 +/- 2 beats/min) and LAC (12 +/- 2 beats/min), and exhibited still greater elevation during LBNP (29 +/- 4 beats/min), yet did not increase during SAC. These results suggest upright posture activates mechanisms that counteract footward fluid redistribution which are not activated during supine applications of simulated gravity. LAC more closely approximated effects of normal gravity (HUT) than LBNP. Therefore, when considering LBNP to simulate gravity, these findings support efforts to reduce the cardiovascular stress imposed by LBNP, while preserving the gravity-like force generated by LBNP.

Watenpaugh, D. E.↗

Role for Lower Extremity Interstitial Fluid Volume Changes in the Development of Orthostasis after Simulated Microgravity

Reentry orthostasis after exposure to the conditions of spaceflight is a persistent problem among astronauts. In a previous study, a computer model systems analysis was used to examine the physiologic mechanisms involved in this phenomenon. In this analysis, it was determined that an augmented capacitance of lower extremity veins due to a fluid volume contracture of the surrounding interstitial spaces during spaceflight results in an increase in sequestered blood volume upon standing and appears to be the initiating mechanism responsible for reentry orthostasis. In this study, we attempt to validate the central premise of this hypothesis using a ground-based spaceflight analog. 10 healthy subjects were placed at bed rest in a 6 head down tilt position for 60 days of bed rest. The impact of adaptations in interstitial fluid volume and venous capacitance in the lower extremities were then observed during a standard tilt test protocol performed before and after the confinement period. The interstitial thickness superficial to the calcaneous immediately below the lateral malleolus was measured using ultrasound with a 17-5 MHz linear array transducer. Measurements of the changes in anterior tibial vein diameter during tilt were obtained by similar methods. The measurements were taken while the subjects were supine and then during upright tilt (80') for thirty minutes, or until the subject had signs of presyncope. Additional measurements of the superficial left tibia interstitial thickness and stroke volume by standard echocardiographic methods were also recorded. In addition, calf compliance was measured over a pressure range of 10-60 mmHg, using plethysmography, in a subset of these subjects (n = 5). There was a average of 6% diminution in the size of the lower extremity interstitial space as compared to measurements acquired prior to bed rest. This contracture of the interstitial space coincided with a subsequent relative increase in the percentage change in tibial vein diameter and stroke volume upon tilting in contrast to the observations made before bed rest (54 vs 23% respectively). Compliance in the calf increased by an average of 36% by day 27 of bedrest. A systems analysis using a computer model of cardiovascular physiology suggests that microgravity induced interstitial volume depletion results in an accentuation of venous blood volume sequestration and is the initiating event in reentry orthostasis. This hypothesis was tested in volunteer subjects using a ground-based spaceflight analog model that simulated the body fluid redistribution induced by microgravity exposure. Measurements of changes in the interstitial spaces and observed responses of the anterior tibial vein with tilt, together with the increase in calf compliance, were consistent with our proposed mechanism for the initiation of postflight orthostasis often seen in astronauts.

Platts, Steven H.↗

Effects of static orientation upon human optokinetic afternystagmus

"Normal" human subjects were placed in a series of 5 static orientations with respect to gravity and were asked to view an optokinetic display moving at a constant angular velocity. The axis of rotation coincided with the subject's rostro-caudal axis and produced horizontal optokinetic nystagmus and afternystagmus. Wall (1) previously reported that these optokinetic afternystagmus responses were not well characterized by parametric fits to slow component velocity. The response for nose-up, however, was larger than for nose-down. This suggested that the horizontal eye movements measured during optokinetic stimulation might include an induced linear VOR component as presented in the body of this paper. To investigate this hypothesis, another analysis of these data has been made using cumulative slow component eye position. Some subjects' responses had reversals in afternystagmus direction. These reversals were "filled in" by a zero slow component velocity. This method of analysis gives a much more consistent result across subjects and shows that, on average, responses from the nose-down horizontal (prone) orientation are greatly reduced (p < 0.05) compared to other horizontal and vertical orientations. Average responses are compared to responses predicted by a model previously used to predict successfully the responses to post-rotatory nystagmus after earth horizontal axis rotation. Ten of 11 subjects had larger responses in their supine than their prone orientation. Application of horizontal axis optokinetic afternystagmus for clinical otolith function testing, and implications for altered gravity experiments are discussed.

Non-NASA Center↗

Behavioral Assessment of Spaceflight Effects on Neurocognitive Performance: Extent and Longevity

Exposure to the microgravity environment during spaceflight missions impacts crewmembers' sensorimotor function. Bock et al. [1] studied the cognitive demands of human sensorimotor performance and dual tasking during long duration missions and concluded that both stress and scarcity of cognitive resources required for sensorimotor adaptation may be responsible for these deficits during spaceflight. Therefore, in consideration of the health and performance of crewmembers in- and post-flight, we are conducting this study to investigate the effects of spaceflight on the extent, longevity and neural bases of sensorimotor, cognitive, and neural changes. The data presented will focus on the behavioral measures that were collected pre-, in- and post-flight including spatial cognition, processing speed, bimanual coordination, functional mobility, computerized dynamic posturography (CDP), and vibrotactile induced vestibular evoked myogenic potential (VEMP). To date, data were collected over the course of two pre-flight sessions and four post-flight sessions on five crewmembers (n=13) using the protocol described in Koppelmans et al. [2]. Balance control was assessed using CDP, with eyes closed and a sway-referenced base of support (Sensory Organization Test 5), with and without head movements in the pitch plane. Spatial working memory was assessed using Thurston's Card Rotation Test and a Mental Rotation Test. The Rod and Frame Test was performed to test visual dependence. The Digit Symbol Substitution Test was performed to evaluate processing speed, and the Purdue Pegboard Task was performed to test bimanual coordination. Vestibular function was assessed by eliciting ocular VEMP via a hand held striker on the side of the head as subjects lay supine on a gurney. Subjects also performed the Functional Mobility Test of walking through an obstacle course to assess rate of early motor learning. Data were also collected on the same crewmembers during three in-flight sessions on the International Space Station (ISS). In-flight, spatial working memory was assessed using the Mental Rotation Test, adaptation to visuo-motor transformation in manual control was assessed using the Sensorimotor Adaptation Test, and multi-tasking ability was assessed using the Dual Task Test. These three tests were performed in a strapped-in configuration mimicking a seated position - waist bungees pulled the crewmember toward the "floor" with feet secured in foot loops. The Mental Rotation Test was also performed in a free-floating configuration while the crewmember floated while holding on to the gamepad controller used to provide input that was secured to the equipment rack on the ISS. Preliminary findings from data collected to date, will be included in the presentation. Eventual comparison to results from supporting bed rest and longitudinal studies will enable the parsing out of the multiple mechanisms contributing to any observed spaceflight-induced sensorimotor and cognitive behavioral changes.

De Dios, Y. E.↗

Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.

Non-NASA Center↗

The ratio of animal protein intake to potassium intake is a predictor of bone resorption in space flight analogues and in ambulatory subjects

BACKGROUND: Bone loss is a critical concern for space travelers, and a dietary countermeasure would be of great benefit. Dietary protein and potassium-associated bicarbonate precursors may have opposing effects on the acid-base balance in the body and therefore on bone loss. OBJECTIVE: In 2 studies, we examined the ability of dietary protein and potassium to predict markers of bone metabolism. DESIGN: In the first study, 8 pairs of male identical twins were assigned to 1 of 2 groups: bed rest (sedentary, or SED, group) or bed rest with supine treadmill exercise in a lower-body negative pressure chamber (EX group). In a second study, groups of 4 subjects lived in a closed chamber for 60 or 91 d, and dietary data were collected for two or three 5-d sessions. Urinary calcium, N-telopeptide, and pyridinium cross-links were measured before bed rest; on bed rest days 5-6, 12-13, 19-20, and 26-27; and daily during the chamber studies. Data were analyzed by Pearson's correlation (P < 0.05). RESULTS: The ratio of animal protein intake to potassium intake was significantly correlated with N-telopeptide in the SED group during bed rest weeks 3 and 4 (r = 0.77 and 0.80) and during the 91-d chamber study (r = 0.75). The ratio of animal protein intake to potassium intake was positively correlated with pyridinium cross-links before bed rest in the EX group (r = 0.83), in the EX group during bed rest week 1 (r = 0.84), and in the SED group during bed rest week 2 (r = 0.72) but not during either chamber study. In both studies, these relations were not significant with the ratio of vegetable protein intake to potassium intake. CONCLUSIONS: The ratio of animal protein intake to potassium intake may affect bone in ambulatory and bed-rest subjects. Changing this ratio may help to prevent bone loss on Earth and during space flight.

Clinical Trial↗

Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms

The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.

Non-NASA Center↗