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Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre

When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

Non-NASA Center

Space flight affects magnocellular supraoptic neurons of young prepuberal rats: transient and permanent effects

Effects of microgravity on postural control and volume of extracellular fluids as well as stress associated with space flight may affect the function of hypothalamic neurosecretory neurons. Since environmental modifications in young animals may result in permanent alterations in neuroendocrine function, the present study was designed to determine the effect of a space flight on oxytocinergic and vasopressinergic magnocellular hypothalamic neurons of prepuberal rats. Fifteen-day-old Sprague-Dawley female rats were flown aboard the Space Shuttle Columbia (STS-90, Neurolab mission, experiment 150) for 16 days. Age-matched litters remained on the ground in cages similar to those of the flight animals. Six animals from each group were killed on the day of landing and eight animals from each group were maintained under standard vivarium conditions and killed 18 weeks after landing. Several signs of enhanced transcriptional and biosynthetic activity were observed in magnocellular supraoptic neurons of flight animals on the day of landing compared to control animals. These include increased c-Fos expression, larger nucleoli and cytoplasm, and higher volume occupied in the neuronal perikaryon by mitochondriae, endoplasmic reticulum, Golgi apparatus, lysosomes and cytoplasmic inclusions known as nematosomes. In contrast, the volume occupied by neurosecretory vesicles in the supraoptic neuronal perikarya was significantly decreased in flight rats. This decrease was associated with a significant decrease in oxytocin and vasopressin immunoreactive levels, suggestive of an increased hormonal release. Vasopressin levels, cytoplasmic volume and c-Fos expression returned to control levels by 18 weeks after landing. These reversible effects were probably associated to osmotic stimuli resulting from modifications in the volume and distribution of extracellular fluids and plasma during flight and landing. However, oxytocin levels were still reduced at 18 weeks after landing in flight animals compared to controls. This indicates that space flight during prepuberal age may induce irreversible modifications in the regulation of oxytocinergic neurons, which in turn may result in permanent endocrine and behavioral impairments.

NASA Experiment Number 9301150

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Non-NASA Center

Neural readaptation to Earth's gravity following return from space

The consequence of exposure to microgravity on the otolith organs was studied by recording the responses of vestibular nerve afferents supplying the utricular otolith organ to inertial accelerations in four toadfish, Opsanus tau, sequentially for 5 days following two National Aeronautics and Space Administration shuttle orbital flights. Within the first day postflight, the magnitude of response to an applied translation was on average three times greater than for controls. The reduced gravitational acceleration in orbit apparently resulted in an upregulation of the sensitivity of utricular afferents. By 30 h postflight, responses were statistically similar to control. The time course of return to normal afferent sensitivity parallels the reported decrease in vestibular disorientation in astronauts following return from space.

manned

Sleep and respiration in microgravity

Sleep studies conducted during the STS-90 Neurolab mission are explored. The relationship between sleep, melatonin, and circadian phase is reviewed. The study contained both sleep and awake components. The objectives of the sleep component were to test five hypotheses: that circadian rhythms of core body temperature and urinary melatonin are synchronized to required sleep-wake schedules, that spaceflight results in substantial disruption of sleep, that the pattern of chest and abdominal wall motion alters during the different sleep stages in microgravity, that arterial oxygen saturation is reduced during some stages of sleep in microgravity, and that pre-sleep administration of melatonin during microgravity results in improved sleep quality. The awake component tested three hypotheses: that ventilatory response to carbon dioxide is increased during exposure to microgravity and that this exacerbates sleep disruption, that ventilatory response to hypoxia is increased by exposure to microgravity, and that the improved sleep resulting from the pre-sleep administration of melatonin enhances next day cognition when compared to placebo.

Non-NASA Center

Overview of the Neurolab Spacelab mission

Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.

manned

EDEN: a payload dedicated to neurovestibular research for Neurolab

The European Space Agency contributes to the Neurolab mission through the delivery of the ESA Developed Elements for Neurolab (EDEN). Those elements include one set supporting the Autonomic Nervous System experiment and one set supporting the Neurovestibular (so-called ATLAS) experiment. This second set is called the Visual and Vestibular Investigation System (VVIS). This paper describes the main characteristics of the VVIS and its various subsystems. The scientific objectives and operational constraints of the ATLAS experiment to be carried out with this equipment during Neurolab are presented to underline the correspondence between the VVIS design and the scientific requirements. Further scientific and technical perspectives for the VVIS, particularly within the scope of the International Space station, are also proposed.

Non-NASA Center

Perception of tilt (somatogravic illusion) in response to sustained linear acceleration during space flight

During the 1998 Neurolab mission (STS-90), four astronauts were exposed to interaural and head vertical (dorsoventral) linear accelerations of 0.5 g and 1 g during constant velocity rotation on a centrifuge, both on Earth and during orbital space flight. Subjects were oriented either left-ear-out or right-ear-out (Gy centrifugation), or lay supine along the centrifuge arm with their head off-axis (Gz centrifugation). Pre-flight centrifugation, producing linear accelerations of 0.5 g and 1 g along the Gy (interaural) axis, induced illusions of roll-tilt of 20 degrees and 34 degrees for gravito-inertial acceleration (GIA) vector tilts of 27 degrees and 45 degrees , respectively. Pre-flight 0.5 g and 1 g Gz (head dorsoventral) centrifugation generated perceptions of backward pitch of 5 degrees and 15 degrees , respectively. In the absence of gravity during space flight, the same centrifugation generated a GIA that was equivalent to the centripetal acceleration and aligned with the Gy or Gz axes. Perception of tilt was underestimated relative to this new GIA orientation during early in-flight Gy centrifugation, but was close to the GIA after 16 days in orbit, when subjects reported that they felt as if they were 'lying on side'. During the course of the mission, inflight roll-tilt perception during Gy centrifugation increased from 45 degrees to 83 degrees at 1 g and from 42 degrees to 48 degrees at 0.5 g. Subjects felt 'upside-down' during in-flight Gz centrifugation from the first in-flight test session, which reflected the new GIA orientation along the head dorsoventral axis. The different levels of in-flight tilt perception during 0.5 g and 1 g Gy centrifugation suggests that other non-vestibular inputs, including an internal estimate of the body vertical and somatic sensation, were utilized in generating tilt perception. Interpretation of data by a weighted sum of body vertical and somatic vectors, with an estimate of the GIA from the otoliths, suggests that perception weights the sense of the body vertical more heavily early in-flight, that this weighting falls during adaptation to microgravity, and that the decreased reliance on the body vertical persists early post-flight, generating an exaggerated sense of tilt. Since graviceptors respond to linear acceleration and not to head tilt in orbit, it has been proposed that adaptation to weightlessness entails reinterpretation of otolith activity, causing tilt to be perceived as translation. Since linear acceleration during in-flight centrifugation was always perceived as tilt, not translation, the findings do not support this hypothesis.

STS-90 Shuttle Project

Ocular counterrolling induced by centrifugation during orbital space flight

During the 1998 Neurolab mission (STS-90), four astronauts were exposed to interaural centripetal accelerations (Gy centrifugation) of 0.5 g and 1 g during rotation on a centrifuge, both on Earth and during orbital space flight. Subjects were oriented either left-ear out or right-ear out, facing or back to motion. Binocular eye movements were measured in three dimensions using a video technique. On Earth, tangential centrifugation that produces 1 g of interaural linear acceleration combines with gravity to tilt the gravitoinertial acceleration (GIA) vector 45 degrees in the roll plane relative to the head vertical, generating a summed vector of 1.4 g. Before flight, this elicited mean ocular counterrolling (OCR) of 5.7 degrees. Due to the relative absence of gravity during flight, there was no linear acceleration along the dorsoventral axis of the head. As a result, during in-flight centrifugation, gravitoinertial acceleration was strictly aligned with the centripetal acceleration along the interaural axis. There was a small but significant decrease (mean 10%) in the magnitude of OCR in space (5.1 degrees). The magnitude of OCR during postflight 1 g centrifugation was not significantly different from preflight OCR (5.9 degrees). Findings were similar for 0.5 g centrifugation, but the OCR magnitude was approximately 60% of that induced by centrifugation at 1 g. OCR during pre- and postflight static tilt was not significantly different and was always less than OCR elicited by centrifugation of Earth for an equivalent interaural linear acceleration. In contrast, there was no difference between the OCR generated by in-flight centrifugation and by static tilt on Earth at equivalent interaural linear accelerations. These data support the following conclusions: (1) OCR is generated predominantly in response to interaural linear acceleration; (2) the increased OCR during centrifugation on Earth is a response to the head dorsoventral 1 g linear acceleration component, which was absent in microgravity. The dorsoventral linear acceleration could have activated either the otoliths or body-tilt receptors that responded to the larger GIA magnitude (1.4 g), to generate the increased OCR during centrifugation on Earth. A striking finding was that magnitude of OCR was maintained throughout and after flight. This is in contrast to most previous postflight OCR studies, which have generally registered decreases in OCR. We postulate that intermittent exposure to artificial gravity, in the form of the centripetal acceleration experienced during centrifugation, acted as a countermeasure to deconditioning of this otolith-ocular orienting reflex during the 16-day mission.

Non-NASA Center

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

manned

Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team

Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.

short duration

Experience-dependent development of spinal motor neurons

Locomotor activity in many species undergoes pronounced alterations in early postnatal life, and environmental cues may be responsible for modifying this process. To determine how these events are reflected in the nervous system, we studied rats reared under two different conditions-the presence or absence of gravity-in which the performance of motor operations differed. We found a significant effect of rearing environment on the size and complexity of dendritic architecture of spinal motor neurons, particularly those that are likely to participate in postural control. These results provide evidence that neurons subserving motor function undergo activity-dependent maturation in early postnatal life in a manner analogous to sensory systems.

STS-90 Shuttle Project

Preparing for Mars: the physiologic and medical challenges

As the twentieth century closes, retrospectives cite the Apollo moon missions as one of the important events of the past 100 years. A trip to Mars, however, would be even more challenging and significant. A round-trip Mars journey would require nearly three years away from Earth, a significant leap in complexity compared to the two week long Moon trips or the record-breaking fourteen-month flight on Mir. What would be the physiologic and medical challenges of a Mars flight? Two key areas of physiology present the greatest potential problems--calcium metabolism and radiation exposure. Data from Mir missions show that bone loss continues in space despite an aggressive countermeasure program. Average losses were 0.35% per month, but some load bearing areas lost >1% per month. A 1% loss rate, if it continued unabated for 30 months, could produce osteoporosis. Smaller losses could still increase fracture risk. Some bone loss can be well tolerated, particularly if the bone can be regained after the mission. But the effectiveness of post-flight rehabilitation to restore the density and quality of bone after spaceflight is not well known. Bone loss estimates are based on continuous weightlessness exposure, but this is not a requirement for a Mars trip. Most of the time on a Mars trip will be spent in the 1/3 Earth's gravity environment on Mars, and either intermittent or continuous artificial gravity can be provided for the transit between planets (although at an engineering cost). The dosing of the gravity exposure (e.g. the level and duration), however, has not been established. Radiation protection also requires a balance between engineering cost and human health. Excessive shielding could add billions of dollars to the cost of a mission. Trips in interplanetary space, however, expose the crew to heavy high-energy particles from cosmic rays (HZE particles), which have a high linear energy transfer. This high energy leads to significant biological damage (e.g. chromosomal aberrations, cancer induction). A recent report from the Committee on Space Biology and Medicine notes that only one systematic study of cancer induction from high-energy particles has been conducted (using the mouse Harderian gland). Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data. Other areas of physiology also present problems, such as muscle loss, cardiovascular deconditioning, and vestibular adaptation. Despite all the issues, however, a focussed, aggressive research program that uses the resources of the International Space Station should pave the way for mankind's greatest adventure--a trip to Mars.

STS-90 Shuttle Project

Spatial orientation of optokinetic nystagmus and ocular pursuit during orbital space flight

On Earth, eye velocity of horizontal optokinetic nystagmus (OKN) orients to gravito-inertial acceleration (GIA), the sum of linear accelerations acting on the head and body. We determined whether adaptation to micro-gravity altered this orientation and whether ocular pursuit exhibited similar properties. Eye movements of four astronauts were recorded with three-dimensional video-oculography. Optokinetic stimuli were stripes moving horizontally, vertically, and obliquely at 30 degrees/s. Ocular pursuit was produced by a spot moving horizontally or vertically at 20 degrees/s. Subjects were either stationary or were centrifuged during OKN with 1 or 0.5 g of interaural or dorsoventral centripetal linear acceleration. Average eye position during OKN (the beating field) moved into the quick-phase direction by 10 degrees during lateral and upward field movement in all conditions. The beating field did not shift up during downward OKN on Earth, but there was a strong upward movement of the beating field (9 degrees) during downward OKN in the absence of gravity; this likely represents an adaptation to the lack of a vertical 1-g bias in-flight. The horizontal OKN velocity axis tilted 9 degrees in the roll plane toward the GIA during interaural centrifugation, both on Earth and in space. During oblique OKN, the velocity vector tilted towards the GIA in the roll plane when there was a disparity between the direction of stripe motion and the GIA, but not when the two were aligned. In contrast, dorsoventral acceleration tilted the horizontal OKN velocity vector 6 degrees in pitch away from the GIA. Roll tilts of the horizontal OKN velocity vector toward the GIA during interaural centrifugation are consistent with the orientation properties of velocity storage, but pitch tilts away from the GIA when centrifuged while supine are not. We speculate that visual suppression during OKN may have caused the velocity vector to tilt away from the GIA during dorsoventral centrifugation. Vertical OKN and ocular pursuit did not exhibit orientation toward the GIA in any condition. Static full-body roll tilts and centrifugation generating an equivalent interaural acceleration produced the same tilts in the horizontal OKN velocity before and after flight. Thus, the magnitude of tilt in OKN velocity was dependent on the magnitude of interaural linear acceleration, rather than the tilt of the GIA with regard to the head. These results favor a 'filter' model of spatial orientation in which orienting eye movements are proportional to the magnitude of low frequency interaural linear acceleration, rather than models that postulate an internal representation of gravity as the basis for spatial orientation.

Flight Experiment

Microgravity Workstation and Restraint Evaluations

Confined workstations, where the operator has limited visibility and physical access to the work area, may cause prolonged periods of unnatural posture. Impacts on performance, in terms of fatigue and posture, may occur especially if the task is tedious and repetitive or requires static muscle loading. The glovebox design is a good example of the confined workstation concept. Within the scope of the 'Microgravity Workstation and Restraint Evaluation' project, funded by the NASA Headquarters Life Sciences Division, it was proposed to conduct a series of evaluations in ground, KC-135 and Shuttle environments to investigate the human factors issues concerning confined/unique workstations, such as gloveboxes, and also including crew restraint requirements. As part of the proposed integrated evaluations, two Shuttle Detailed Supplementary Objectives (DSOs) were manifested; one on Space Transportation System (STS)-90 and one on STS-88. The DSO on STS-90 evaluated use of the General Purpose Workstation (GPWS). The STS-88 mission was planned to evaluate a restraint system at the Remote Manipulator System (RMS). In addition, KC- 1 35 flights were conducted to investigate user/workstation/restraint integration for long-duration microgravity use. The scope of these evaluations included workstations and restraints to be utilized in the ISS environment, but also incorporated other workstations/ restraints in an attempt to provide findings/requirements with broader applications across multiple programs (e.g., Shuttle, ISS, and future Lunar-Mars programs). In addition, a comprehensive electronic questionnaire has been prepared and is under review by the Astronaut Office which will compile crewmembers' lessons learned information concerning glovebox and restraint use following their missions. These evaluations were intended to be complementary and were coordinated with hardware developers, users (crewmembers), and researchers. This report is intended to provide a summary of the findings from each of the evaluations.

Chmielewski, C.