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Exercise thermoregulation after 6 h of chair rest, 6 degrees head-down bed-rest, and water immersion deconditioning in men

The purpose was to investigate the mechanism for the excessive exercise hyperthermia following deconditioning (reduction of physical fitness). Rectal (Tre) and mean skin (Tsk) temperatures and thermoregulatory responses were measured in six men [mean (SD) age, 32 (6) years; mass, 78.26 (5.80) kg; surface area, 1.95 (0.11) m2; maximum oxygen uptake (VO2max), 48 (6) ml.min-1.kg-1; whilst supine in air at dry bulb temperature 23.2 (0.6) degree C, relative humidity 31.1 (11.1)% and air speed 5.6 (0.1) m.min-1] during 70 min of leg cycle exercise [51 (4)% VO2max] in ambulatory control (AC), or following 6 h of chair rest (CR), 6 degree head-down bed rest (BR), and 20 degree (WI20) and 80 degree (WI80) foot-down water immersion [water temperature, 35.0 (0.1) degree C]. Compared with the AC exercise delta Tre [mean (SD) 0.77 (0.13) degree C (*P < 0.05), after WI80 0.96 (0.13) degree C*, and after WI20 1.03 (0.09) degree C*. All Tsk responded similarly to exercise: they decreased (NS) by 0.5-0.7 degree C in minutes 4-8 and equilibrated at +0.1 to +0.5 degree C at 60-70. Skin heat conductance was not different among the five conditions (range = 147-159 kJ.m-2.h-1.degree C-1). Results from an intercorrelation matrix suggested that total body sweat rate was more closely related to Tre at 70 min (Tre70) than limb sweat rate or blood flow. Only 36% of the variability in Tre70 could be accounted for by total sweating, and less than 10% from total body dehydration. It would appear that multiple factors are involved which may include change in sensitivity of thermo- and osmoreceptors.

NASA Discipline Regulatory Physiology

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.

Effect of bed rest and exercise on body balance

A battery of 11 body balance tests was administered to 7 men before and after 14 days of bedrest. Seven men who had not undergone bed rest served as controls. During bed rest, each subject underwent daily either isotonic, isometric, or no leg exercise. The results showed that, for the bed-rested no exercise, isotonic exercise, and isometric exercise groups, 2 weeks of bed rest produces significant body balance decrements on 3, 4, and 5 of the 11 tests, respectively. Daily leg exercise did not prevent the debilitating effects of bed rest on body balance. After bed rest, balance skill was relearned rapidly so that in most tests, performance had reached prebed-rest levels by the third recovery day. These data suggest that balance impairment is not due to loss of muscular strength in the legs but, perhaps, to a bed-rest-related change in the neurally coded information to postural control centers.

Haines, R. F.

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.

NASA Discipline Cardiopulmonary

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

NASA Discipline Number 26-10

Simulated microgravity [bed rest] has little influence on taste, odor or trigeminal sensitivity

Anecdotal evidence suggests that astronauts' perceptions of foods in space flight may differ from their perceptions of the same foods on Earth. Fluid shifts toward the head experienced in space may alter the astronauts' sensitivity to odors and tastes, producing altered perceptions. Our objective was to determine whether head-down bed rest, which produces similar fluid shifts, would produce changes in sensitivity to taste, odor or trigeminal sensations. Six subjects were rested three times prior to bed rest, three times during bed rest and two times after bed rest to determine their threshold sensitivity to the odors isoamylbutyrate and menthone, the tastants sucrose, sodium chloride, citric acid, quinine and monosodium glutamate, and to capsaicin. Thresholds were measured using a modified staircase procedure. Self-reported congestion was also recorded at each test time. Thresholds for monosodium glutamate where slightly higher during bed rest. None of the other thresholds were altered by bed rest.

NASA Center JSC

Focal Gray Matter Plasticity as a Function of Long Duration Head-down Tilt Bed Rest

Long duration spaceflight (i.e., > or = 22 days) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes may be related to structural and functional brain changes is yet unknown. However, experimental studies revealed changes in the gray matter (GM) of the brain after simulated microgravity. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning and motor behavior. Long duration head-down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on the brain. VBM analysis revealed a progressive decrease from pre- to in- bed rest in GM volume in bilateral areas including the frontal medial cortex, the insular cortex and the caudate. Over the same time period, there was a progressive increase in GM volume in the cerebellum, occipital-, and parietal cortex, including the precuneus. The majority of these changes did not fully recover during the post-bed rest period. Analysis of lobular GM volumes obtained with BRAINS showed significantly increased volume from pre-bed rest to in-bed rest in GM of the parietal lobe and the third ventricle. Temporal GM volume at 70 days in bed rest was smaller than that at the first pre-bed rest measurement. Trend analysis showed significant positive linear and negative quadratic relationships between parietal GM and time, a positive linear relationship between third ventricle volume and time, and a negative linear relationship between cerebellar GM volume and time. FM performance improved from pre-bed rest session 1 to session 2. From the second pre-bed rest measure to the last-day-in-bed rest, there was a significant decrease in performance that only partially recovered post-bed rest. No significant association was observed between changes in brain volume and changes in functional mobility. Extended bed rest, which is an analog for microgravity, can result in local volumetric GM increase and decrease and adversely affect functional mobility. These changes in brain structure and performance were not related in this sample. Whether the effects of bed rest dissipate at longer times post-bed rest, and if they are associated with behavior are important questions that warrant further research including more subjects and longer follow-up times.

Koppelmans, V.

Bed rest suppresses bioassayable growth hormone release in response to muscle activity

Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P < 0.05) BGH by 66% at -13 or -12 days (2,146 +/- 192 to 3,565 +/- 197 microg/l) and by 92% at -8 or -7 days (2,162 +/- 159 to 4,161 +/- 204 microg/l). After 2 or 3 days of bed rest, there was no response of BGH to the muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

Non-NASA Center

Effects of Bed Rest on Conduction Velocity of the Triceps Surae Stretch Reflex and Postural Control

Despite rigorous exercise and nutritional management during space missions, astronauts returning from microgravity exhibit neuromuscular deficits and a significant loss in muscle mass in the postural muscles of the lower leg. Similar changes in the postural muscles occur in subjects participating in long-duration bed rest studies. These adaptive muscle changes manifest as a reduction in reflex conduction velocity during head-down bed rest. Because the stretch reflex encompasses both the peripheral (muscle spindle and nerve axon) and central (spinal synapse) components involved in adaptation to calf muscle unloading, it may be used to provide feedback on the general condition of neuromuscular function, and might be used to evaluate the effectiveness of countermeasures aimed at preserving muscle mass and function during periods of unloading. Stretch reflexes were measured on 18 control subjects who spent 60 to 90 days in continuous 6 deg head-down bed rest. Using a motorized system capable of rotating the foot around the ankle joint (dorsiflexion) through an angle of 10 degrees at a peak velocity of about 250 deg/sec, a stretch reflex was recorded from the subject's left triceps surae muscle group. Using surface electromyography, about 300 reflex responses were obtained and ensemble-averaged on 3 separate days before bed rest, 3 to 4 times in bed, and 3 times after bed rest. The averaged responses for each test day were examined for reflex latency and conduction velocity (CV) across gender. Computerized posturography was also conducted on these same subjects before and after bed rest as part of the standard measures. Peak-to-peak sway was measured during Sensory Organization Tests (SOTs) to evaluate changes in the ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Although no gender differences were found, a significant increase in reflex latency and a significant decrease in CV were observed during the bed rest period, with a return to baseline 3 to 5 days after bed rest, depending on the duration of bed rest. In addition, a relationship between CV and loss of muscle strength in the lower leg was observed post bed rest for most subjects. Immediately post-bed rest, most subjects showed decreased performance on SOTs, with the greater decrements on sway-referenced support and head movement conditions. Post-bed rest decrements were less than typically observed following spaceflight. Decrements in postural control and the stretch reflex can be primarily attributed to the unloading mechanisms this ground-based analog provides. The stretch reflex is a concise test measurement that can be obtained during the head-down phase of bed rest, as it does not interfere with the bed rest paradigm. This makes it an ideal tool that can detect, early on, whether a countermeasure is successful in preserving muscle function.

Reschke, M. F.

Effects of acute exercise on attenuated vagal baroreflex function during bed rest

We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 deg head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4 percent (p less than 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p less than 0.05) by 10.7 +/- 3.7 percent above pre-bed rest levels and 34.3 +/- 7.9 percent above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.

Convertino, Victor A.

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.

Cognitive Functioning in Long Duration Head-down Bed Rest

The Space Flight Cognitive Assessment Tool for Windows (WinSCAT) is a self-administered battery of tests used on the International Space Station for evaluating cognitive functioning. Here, WinSCAT was used to assess cognitive functioning during extended head-down bed rest. Thirteen subjects who participated in 60 or 90 days of 6 deg head-down bed rest took WinSCAT during the pre-bed rest phase, the in-bed rest phase, and the post-bed rest (reconditioning) phase of study participation. After adjusting for individual baseline performance, 12 off-nominal scores were observed out of 351 total observations during bed rest and 7 of 180 during reconditioning. No evidence was found for systematic changes in off-nominal incidence as time in bed rest progressed, or during the reconditioning period. Cognitive functioning does not appear to be adversely affected by long duration head-down bed rest. Individual differences in underlying cognitive ability and motivation level are likely explanations for the current findings.

Seaton, Kimberly A.

A Comparison of Tandem Walk Performance Between Bed Rest Subjects and Astronauts

Astronauts experience a microgravity environment during spaceflight, which results in a central reinterpretation of both vestibular and body axial-loading information by the sensorimotor system. Subjects in bed rest studies lie at 6deg head-down in strict bed rest to simulate the fluid shift and gravity-unloading of the microgravity environment. However, bed rest subjects still sense gravity in the vestibular organs. Therefore, bed rest isolates the axial-unloading component, thus allowing for the direct study of its effects. The Tandem Walk is a standard sensorimotor test of dynamic postural stability. In a previous abstract, we compared performance on a Tandem Walk test between bed rest control subjects, and short- and long-duration astronauts both before and after flight/bed rest using a composite index of performance, called the Tandem Walk Parameter (TWP), that takes into account speed, accuracy, and balance control. This new study extends the previous data set to include bed rest subjects who performed exercise countermeasures. The purpose of this study was to compare performance during the Tandem Walk test between bed rest subjects (with and without exercise), short-duration (Space Shuttle) crewmembers, and long-duration International Space Station (ISS) crewmembers at various time points during their recovery from bed rest or spaceflight.

Miller, Chris

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Non-NASA Center

Joint US/USSR study: Comparison of effects of horizontal and head-down bed rest

An account is given of the results of the first joint U.S./U.S.S.R. bed rest study. The study was accomplished in two parts: A soviet part (May to June 1979) and an American part (July to August 1979). Both studies were conducted under identical conditions and provided a basis for comparison of physiologic reactions and standardizing procedures and methods. Each experiment consisted of three periods: 14 days of pre-bed rest control, 7 days of bed rest, and a 10 to 14 day recovery period. Ten males participated in each study, with five subjects experiencing horizontal bed rest and five subjects a -6 deg head-down body position. Biochemical and hormonal measurements were made of blood and urine, with particular attention to electrolyte metabolism and kidney function; cardio-pulmonary changes at rest and exercise; influence of Lower Body Negative Pressure (LBNP); and incremental exercise using a bicyle ergometer while supine and sitting. Expected moderate changes were noted to occur for various physiologic parameters. Clinical evidence pointed to the fact that head-down bed rest when compared to horizontal conditions more closely matched the conditions seen after manned spaceflight. For the most part, statistically significant differences between the two body positions were not observed.

Sandler, Harold

Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin associated with decreased serum PTH and elevated bone resorption markers in otherwise healthy men subjected to long-term immobilization.

Spatz, J. M.

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Mean IOP significantly increased while at 6deg HDT and returned towards pre-bed rest values upon leaving bed rest. While mean IOP increased during bed rest, it remained within the normal limits for subject safety. A diuretic shift and cardiovascular deconditioning occurs during in-bed rest, as expected. There was no demonstrable correlation between the largest change in IOP (pre/post) and cardiovascular measure changes (pre/post). Additional mixed effects linear regression modeling may reveal some subclinical physiological changes that might assist in describing the VIIP syndrome pathophysiology.

Cromwell, R. L.

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

Pace, N.