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The absence of unit gravity may cause physiological changes in the cardiovascular system. For instance, in the absence of Earth's gravity, venous return to the heart may increase due, in pan, to decreased pooling of the blood in the extremities. We hypothesize that this would produce an increase in the heart's work load ultimately resulting in hypertrophy.
In our original application we proposed to investigate the effects of gravity on the formation of connections between the gravity receptors of the ear and the brain in rat pups raised in space beginning at an age before these connections are made until near the time of birth, when they are to some extent functional. We used the neuronal tracer, Dil, which could be applied to tissue obtained immediately after landing of the space shuttle, thus minimizing changes due to the earth's gravity. We hoped to determine whether the vestibular system develops in two phases, as do other sensory systems (such as the visual system). In these other systems the first phase of development is controlled genetically and the second phase is controlled by environmental stimulation. Our data collected strongly supports the idea that the vestibular system has these same two phases of development. The tissue obtained from the NIH.R1 experiment was of exceptionally high quality for our analysis. Therefore, we expanded our investigation into the ultrastructural effects of microgravity on vestibular development. For the sake of clarity we will subdivide our summary into two categories: (1) analysis of the branching pattern of axons between the vestibular nerve and the gravistatic receptors of the ear in flight and control animals, and (2) analysis of the branching pattern of axons between the vestibular nerve and the brain in flight and control animals.
The data confirm previous findings that quail embryos can, under proper circumstances, develop until hatching in microgravity. There were no gross abnormalities in the few ears of the late embryos (we received 3 ears at E14.5 and 4 ears at E16.5). Due to inadequate numbers of samples returned and their fully insufficient fixation, no conclusions could be reached that warrant any publications.
Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.
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.
No abstract available
The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.
Vitamin D deficiency has reemerged as a public health concern in the United States. It is also a concern for astronauts because spacecraft are shielded from ultraviolet light, leaving diet as the sole source of vitamin D. We report here the findings from four studies: one evaluation of astronauts before and after 4- to 6-month missions to the International Space Station, and the other three from a ground-based analog for space flight, long-term bed rest. For the space flight study, blood samples were collected before the flight and within hours of landing after it. Crewmembers (n = 11) were provided vitamin D supplements (as cholecalciferol (10 g/d) throughout the mission. The average number of vitamin D supplements reported to be consumed per week was 5.7 plus or minus 4.0. The vitamin D status indicator serum 25-hydroxycholecalciferol was 25% less after landing (48 plus or minus 20) than before flight (63 plus or minus 16) (P less than 0.01). A series of three studies was undertaken to evaluate nutritional changes during and after 60 or 90 days of -6 deg. head-down-tilt bed rest. A total of 11 subjects (8 M, 3 F; age 26-55 y) participated in the studies. Blood and urine were collected twice before bed rest and once per month during bed rest. During bed rest the average dietary intake of vitamin D for the three studies was 4.84 plus or minus 0.16 (study 1), 6.24 plus or minus 0.81 (study 2), and 7.16 plus or minus 1.40 (study 3) micrograms/day. In study 1 only, subjects were given a daily supplement of 10 g vitamin D (as ergocalciferol). Data were analyzed using repeated-measures ANOVA. In the first study, 7 days after the end of the bed rest, serum 25-hydroxycholecalciferol was 30% less than it was before bed rest (p less than 0.05). In the second and third studies, during or after bed rest the serum 25-hydroxycholecalciferol concentration was not significantly different from its concentration before bed rest. These data demonstrate that vitamin D intake is critical for individuals not exposed to the sun. Although we studied astronauts and healthy subjects in bed rest, the implications of our results also apply to people living in northern latitudes and others who receive little exposure to sunlight, such as elderly people who seldom go outdoors. The inability of supplements to maintain vitamin D status is also an important finding, and highlights the need for careful food selection to ensure adequate vitamin D intake.
Historically, less than 20 percent of crew time related to extravehicular activity (EVA) is spent on productive external work.1 A single-person spacecraft with 90 percent efficiency provides productive new capabilities for maintaining the International Space Station (ISS), exploring asteroids, and servicing telescopes or satellites. With suits, going outside to inspect, service or repair a spacecraft is time-consuming, requiring pre-breathe time, donning a fitted space suit, and pumping down an airlock. For ISS, this is between 12.5 and 16 hours for each EVA, not including translation and work-site set up. The work is physically demanding requiring a day of rest between EVAs and often results in suit-induced trauma with frequent injury to astronauts fingers2. For maximum mobility, suits use a low pressure, pure oxygen atmosphere. This represents a fire hazard and requires pre-breathing to reduce the risk of decompression sickness (bends). With virtually no gravity, humans exploring asteroids cannot use legs for walking. The Manned Maneuvering Unit offers a propulsive alternative however it is no longer in NASA s flight inventory. FlexCraft is a single person spacecraft operating at the same cabin atmosphere as its host so there is no risk of the bends and no pre-breathing. This allows rapid, any-time access to space for repeated short or long EVAs by different astronauts. Integrated propulsion eliminates hand-over-hand translation or having another crew member operate the robotic arm. The one-size-fits-all FlexCraft interior eliminates the suit part inventory and crew time required to fit all astronauts. With a shirtsleeve cockpit, conventional displays and controls are used and because the work is not strenuous no rest days are required. Furthermore, there is no need for hand tools because manipulators are equipped with force multiplying end-effectors that can deliver the precise torque for the job.
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INTRODUCTION Exposure to weightlessness induces a headward fluid shift and redistribution of fluids, resulting in increased internal jugular vein (IJV) cross-sectional area and altered IJV blood flow dynamics, including stasis and retrograde flow. These findings may contribute to various risks of spaceflight, including thrombosis or other risks affected by cerebral venous blood flow. To date, our understanding of the cerebral venous outflow dynamics in weightlessness is limited to the left IJV assessed ~45 and ~150 days into spaceflight. Therefore, it is unknown how quickly the alterations in venous blood flow dynamics change as a result of weightlessness. The purpose of this study is to determine 1) if venous stasis is an immediate effect of weightlessness and therefore a risk for short-duration missions and 2) the effect of weightlessness on brachiocephalic venous flow. METHODS In this study, we investigated the effects of acute weightlessness during parabolic flight on the right and left IJV in 12 healthy subjects. Baseline ultrasound images were obtained on the ground (1g) in the seated and supine postures and during 0g parabolic flight. Each data collection session included 2D ultrasonography to quantify IJV cross-sectional area and Doppler ultrasonography to characterize venous blood flow patterns in the bilateral IJVs. RESULTS There was a similar pattern of response in the left and right IJV area across postures and g-levels. IJV area increased from seated to supine by 0.74 mm2 (95% CI: 0.56 to 0.91 mm2, p<.001) and increased further during weightlessness by 0.29 mm2 (95% CI: 0.11 to 0.47 mm2, p=.0015). IJV Doppler images revealed stagnant flow in the left IJV in one subject during 0g exposure that was not present during any imaging on the ground; the right IJV continued to show pulsatile, nominal flow patterns in both 0g and 1g. CONCLUSIONS This study characterized the immediate effect of the weightlessness-induced headward fluid shift on venous parameters in the left and right IJV. The left IJV appears to be more susceptible to flow alterations, including stagnant flow, during both short and long-duration exposure to weightlessness that may contribute to the risk of thrombosis inflight.
INTRODUCTION Exposure to weightlessness induces a headward fluid shift and redistribution of fluids, resulting in increased internal jugular vein (IJV) cross-sectional area and altered IJV blood flow dynamics including stasis and retrograde flow. These findings may contribute to various risks of spaceflight, including thrombosis or other risks affected by cerebral venous blood flow. To date, our understanding of the cerebral venous outflow dynamics is limited to the left IJV assessed ~45and ~150days into spaceflight. Therefore, it is unknown how quickly the alterations in venous blood flow dynamics change as a result of weightlessness. The purpose of this study is to determine 1) if venous stasis is an immediate effect of weightlessness, and therefore a risk for short-duration missions, and 2) the effect of weightlessness on brachiocephalic venous flow. METHODS In this study, we will determine the effects of acute weightlessness during parabolic flight on right and left IJV cross-sectional area, as well as blood flow dynamics through the IJV and brachiocephalic veins in 12 healthy subjects. Baseline ultrasound images will be obtained on the ground prior to the parabolic flight in the seated and supine postures to determine normal changes in blood flow with posture-induced fluid shifts in a 1genvironment. Subjects will then undergo parabolic flight withrepeated,~20 second exposure to 0g. Each data collection session will include 2D ultrasonography to quantify IJV cross-sectional area and Doppler ultrasonography to characterize venous blood flow patterns in the IJV and brachiocephalic veins. RESULTS Data collection for this study is planned to take place in October, 2021.CONCLUSIONS This study will characterize the immediate venous response in the left and right IJV and brachiocephalic veins upon entry into weightlessness. The results from this parabolic flight study will be compared with previous data from International Space Station crewmembers collectedafter~45 and ~150 days into spaceflight to provide a more complete understanding of the temporal profile of changes in venous blood flow dynamics during weightlessness and whether these findings develop in veins other than the left IJV. Supported by the NASA Human Research Program.
Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins may contribute to the disorders of Ca2+ metabolism induced by space flight.
Despite a number of difficulties in performing experiments during weightlessness, a great deal of information has been obtained concerning the effects of spaceflight on the regulation of body fluid and electrolytes. Many paradoxes and questions remain, however. Although body mass, extracellular fluid volume, and plasma volume are reduced during spaceflight and remain so at landing, the changes in total body water are comparatively small. Serum or plasma sodium and osmolality have generally been unchanged or reduced during the spaceflight, and fluid intake is substantially reduced, especially during the first of flight. The diuresis that was predicted to be caused by weightlessness, has only rarely been observed as an increased urine volume. What has been well established by now, is the occurrence of a relative diuresis, where fluid intake decreases more than urine volume does. Urinary excretion of electrolytes has been variable during spaceflight, but retention of fluid and electrolytes at landing has been consistently observed. The glomerular filtration rate was significantly elevated during the SLS missions, and water and electrolyte loading tests have indicated that renal function is altered during readaptation to Earth's gravity. Endocrine control of fluid volumes and electrolyte concentrations may be altered during weightlessness, but levels of hormones in body fluids do not conform to predictions based on early hypotheses. Antidiuretic hormone is not suppressed, though its level is highly variable and its secretion may be affected by space motion sickness and environmental factors. Plasma renin activity and aldosterone are generally elevated at landing, consistent with sodium retention, but inflight levels have been variable. Salt intake may be an important factor influencing the levels of these hormones. The circadian rhythm of cortisol has undoubtedly contributed to its variability, and little is known yet about the influence of spaceflight on circadian rhythms. Atrial natriuretic peptide does not seem to play an important role in the control of natriuresis during spaceflight. Inflight activity of the sympathetic nervous system, assessed by measuring catecholamines and their metabolites and precursors in body fluids, generally seems to be no greater than on Earth, but this system is usually activated at landing. Collaborative experiments on the Mir and the International Space Station should provide more of the data needed from long-term flights, and perhaps help to resolve some of the discrepancies between U.S. and Russian data. The use of alternative methods that are easier to execute during spaceflight, such as collection of saliva instead of blood and urine, should permit more thorough study of circadian rhythms and rapid hormone changes in weightlessness. More investigations of dietary intake of fluid and electrolytes must be performed to understand regulatory processes. Additional hormones that may participate in these processes, such as other natriuretic hormones, should be determined during and after spaceflight. Alterations in body fluid volume and blood electrolyte concentrations during spaceflight have important consequences for readaptation to the 1-G environment. The current assessment of fluid and electrolyte status during weightlessness and at landing and our still incomplete understanding of the processes of adaptation to weightlessness and readaptation to Earth's gravity have resulted in the development of countermeasures that are only partly successful in reducing the postflight orthostatic intolerance experienced by astronauts and cosmonauts. More complete knowledge of these processes can be expected to produce countermeasures that are even more successful, as well as expand our comprehension of the range of adaptability of human physiologic processes.
Exercise prescriptions completed by International Space Station (ISS) crewmembers are typically based upon evidence obtained during ground-based investigations, with the assumption that the results of long-term training in weightlessness will be similar to that attained in normal gravity. Coupled with this supposition are the assumptions that exercise motions and external loading are also similar between gravitational environments. Normal control of locomotion is dependent upon learning patterns of muscular activation and requires continual monitoring of internal and external sensory input [1]. Internal sensory input includes signals that may be dependent on or independent of gravity. Bernstein hypothesized that movement strategy planning and execution must include the consideration of segmental weights and inertia [2]. Studies of arm movements in microgravity showed that individuals tend to make errors but that compensation strategies result in adaptations, suggesting that control mechanisms must include peripheral information [3-5]. To date, however, there have been no studies examining a gross motor activity such as running in weightlessness other than using microgravity analogs [6-8]. The objective of this evaluation was to collect biomechanical data from crewmembers during treadmill exercise before and during flight. The goal was to determine locomotive biomechanics similarities and differences between normal and weightless environments. The data will be used to optimize future exercise prescriptions. This project addresses the Critical Path Roadmap risks 1 (Accelerated Bone Loss and Fracture Risk) and 11 (Reduced Muscle Mass, Strength, and Endurance). Data were collected from 7 crewmembers before flight and during their ISS missions. Before launch, crewmembers performed a single data collection session at the NASA Johnson Space Center. Three-dimensional motion capture data were collected for 30 s at speeds ranging from 1.5 to 9.5 mph in 0.5 mph increments with a 12-camera system. During flight, each crewmember completed up to 6 data collection sessions spread across their missions, performing their normal exercise prescription for the test day, resulting in varying data collection protocols between sessions. Motion data were collected by a single HD video camera positioned to view the crewmembers' left side, and tape markers were placed on their feet, legs, and neck on specific landmarks. Before data collection, the crewmembers calibrated the video camera. Video data were collected during the entire exercise session at 30 Hz. Kinematic data were used to determine left leg hip, knee, and ankle range of motion and contact time, flight time, and stride time for each stride. 129 trials in weightlessness were analyzed. Mean time-normalized strides were found for each trial, and cross-correlation procedures were used to examine the strength and direction of relationships between segment movement pattern timing in each gravitational condition. Cross-correlation analyses between gravitational conditions revealed highly consistent movement patterns at each joint. Peak correlation coefficients occurred at 0% phase, indicating there were no lags in movement timing. Joint ranges of motion were similar between gravitational conditions, with some slight differences between subjects. Motion patterns in weightlessness were highly consistent at a given speed with those occurring in 1G, indicating that despite differing sensory input, subjects maintain running kinematics. The data suggest that individuals are capable of compensating for loss of limb weight when creating movement strategies. These results have important implications for creating training programs for use in weightlessness as practitioners can have greater confidence in running motions transferring across gravitational environments. Furthermore, these results have implications for use by researchers investigating motor control mechanisms and investigating hypotheses related to movement strategies when using sensory input that is dependent upon gravity.