Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.     

Understanding metabolic alterations in space flight using quantitative models: fluid and energy balance

This report summarizes many of the results obtained during the Skylab program, on metabolic changes during weightlessness. The examination of the data was conducted following an integrated multi-disciplinary and multi-experimental approach. Emphasis is given on several major aspects of metabolic adaptation to space flight: fluid-electrolyte regulation, mechanisms of hormone disturbances, energy balance and etiology of weight loss. The aim is to obtain a composite picture of the fluid, electrolyte and energy response to weightlessness.     

Effect of geomagnetic field disturbances on the adaptive stress reaction of cosmonauts

Investigations of the effect of geomagnetic activity factors on the cardiac rhythm regulation and arterial pressure of cosmonauts during the expeditions onboard the Soyuz spacecraft, and the MIR and ISS orbital space stations was carried out for various durations of flight in weightlessness and, under control. Groups of cosmonauts were inspected under flight conditions outside the geomagnetic disturbances and in ground preflight conditions, during disturbances without them. The presence of specific effect of geomagnetic disturbances on the system of vegetative regulation of blood circulation of cosmonauts during the flight was demonstrated for the first time. The response of cosmonauts’ cardiac rhythm on the magnetic storm is definitely revealed; however, it depends on the initial functional background and, in particular, on the state of mechanisms of vegetative regulation (the duration of flight and adaptation to it).     

Autonomic function testing aboard the ISS using “PNEUMOCARD”

Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the “ISS” have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device “Pneumocard” was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex “Pneumocard” was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates.HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight.Our results demonstrate that autonomic function testing aboard the ISS using “Pneumocard” is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut.Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant and compelling.     

Bright light as a chronobiological countermeasure for shiftwork in space

Work-rest schedules during long duration space missions involve several factors which could disrupt sleep and circadian temporal organisation: (1) displacement of sleep due to two-shift operations; (2) planned or unplanned schedule changes due to operational requirements; (3) social and light Zeitgebers different from those on earth; (4) changes in the gravitational exposure. Timed bright light treatment has the potential to accelerating adaptation to schedule changes. Four male subjects were exposed to two sessions of 11 d of simulated microgravity (6 ° head down tilt bedrest) with 6-h extensions of the wake period on 2 days (12-h phase delay). In a blind crossover design, subjects were exposed to bright light (> 3500 lux) for 5 h on each of the 2 shift days and the following day, at times either expected to accelerate the adjustment to the phase delay (experimental condition) or to have no phase shifting effect (control condition). Sleep was recorded polygraphically, the circadian system was monitored by recordings of heart rate and body temperature, and by collection of urine (electrolyte and hormone excretion). Only the rhythms of 6-hydroxymelatoninsulphate and potassium excretions showed significantly enhanced adjustment under the experimental condition. Different rhythms Actapted to the 12-h delay at different rates, comparable to those observed after time zone shifts. Sleep was shorter in simulated weightlessness than in normal ambulatory age-matched subjects, consistent with the shorter sleep durations characteristic of space flight. These results confirm the disruptive effects of wake-rest schedule shifts on sleep and circadian rhythms. Contrary to our initial hypothesis, 5-h exposures to bright light finishing at the time of the circadian temperature minimum were not more effective at accelerating adjustment to a 12-h schedule delay than exposures coinciding with the temperature maximum. We conclude that, while bright light may accelerate adjustment to work-rest schedule delays, any such effect seems to be largely independent from the timing of the light exposure.     

Effect of weightlessness on sympathetic-adrenomedullary activity of rats.

Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)--as well as CA-degrading enzymes-monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.     

Catecholamines and their enzymes in discrete brain areas of rats after space flight on biosatellites Cosmos

The activity of the catecholaminergic system was measured in the hypothalamus of rats which had experienced an 18.5-19.5-day-long stay in the state of weightlessness during space flights on board Soviet biosatellites of the type Cosmos. In the first two experiments, Cosmos 782 and 936, the concentration of norepinephrine and the activities of synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase and of the degrading enzyme monoamine oxidase were measured in the total hypothalamus. None of the given parameters was changed after space flight. In the light of the changes of these parameters recorded after exposure to acute stress on Earth, this finding indicates that long-term state of weightlessness does not represent an intensive stressogenic stimulus for the system studied. In the space experiment Cosmos 1129, the concentration of norepinephrine, epinephrine, and dopamine was studied in isolated nuclei of the hypothalamus of rats within 6-10 hr following return from space. Norepinephrine was found to be significantly reduced in the arcuate nucleus, median eminence and periventricular nucleus, epinephrine in the median eminence, periventricular and suprachiasmatic nuclei, whereas dopamine was not significantly changed after space flight. The decreased catecholamine levels found in some hypothalamic nuclei of rats which had undergone space flight indicate that no chronic intensive stressor could have acted during the flight, otherwise the catecholamine concentration would have been increased in the nuclei. The decreased levels must have been induced by the effect of a stressogenic factor acting for a short time only, and that either during the landing maneuver or immediately after landing. Thus long-term exposure of the organism to the state of weightlessness does not represent a stressogenic stimulus for the catecholaminergic system in the hypothalamus, which is one of the regulators of the activation of neuroendocrine reactions under stress.     

DARA vestibular equipment onboard MIR

In space, the weightless environment provides a different stimulus to the otolith organs of the vestibular system, and the resulting signals no longer correspond with the visual and other sensory signals sent to the brain. This signal conflict causes disorientation. To study this and also to understand the vestibular adaptation to weightlessness, DARA has developed scientific equipment for vestibular and visuo-oculomotoric investigations. Especially, two video-oculography systems (monocular--VOG--and binocular--BIVOG, respectively) as well as stimuli such as an optokinetic stimulation device have successfully been employed onboard MIR in the frame of national and European missions since 1992. The monocular VOG was used by Klaus Flade during the MIR '92 mission, by Victor Polyakov during his record 15 months stay onboard MIR in 1993/94 as well as by Ulf Merbold during EUROMIR '94. The binocular version was used by Thomas Reiter and Sergej Avdeyev during the 6 months EUROMIR '95 mission. PIs of the various experiments include H. Scherer and A. Clarke (FU Berlin), M. Dieterichs and S. Krafczyk (LMU Munchen) from Germany as well as C.H. Markham and S.G. Diamond from the United States. Video-Oculography (VOG) is a technique for examining the function of the human balance system located in the inner ear (vestibular system) and the visio-oculomotor interactions of the vestibular organ. The human eye movements are measured, recorded and evaluated by state-of-the-art video techniques. The method was first conceived and designed at the Vestibular Research Laboratory of the ENT Clinic in Steglitz, FU Berlin (A. Clarke, H. Scherer). Kayser-Threde developed, manufactured and tested the facilities for space application under contract to DARA. Evaluation software was first provided by the ENT Clinic, Berlin, later by our subcontractor Sensomotoric Instruments (SMI), Teltow. Optokinetic hardware to support visuo-oculomotoric investigations, has been shipped to MIR for EUROMIR '95 and has successfully been used in conjunction with VOG by ESA astronaut Thomas Reiter. Most recently, BIVOG aboard MIR will be reused in the frame of German/Russian joint experiment sessions employing two Russian cosmonauts from August 1997 to January 1998.     

Summary of medical investigations in the U.S.S.R. manned space missions.

The results of biomedical investigations carried out in the U.S.S.R. manned space missions are discussed. Their basic result is well-documented evidence that man can perform space flights of long duration. The investigations have demonstrated no direct correlation between inflight or postflight physiological reactions of crewmembers and flight duration. In all likelihood, this can be attributed to the fact that special exercises done inflight efficiently prevented adverse effects of weightlessness. However, human reactions to weightlessness need further study. They include negative calcium balance and anemia as well as vestibulo-autonomic disorders shown by crewmembers at early stages of weightlessness. Attention should be given to psychological, social-psychological and ethical problems that may also limit further increase in flight duration.     

Endocrine responses in long-duration manned space flight

The bioassay of body fluids experiment is designed to evaluate the biochemical adaptation resulting from extended exposure to space flight environment by identifying changes in hormonal and associated fluid and electrolyte parameters reflected in the blood and urine of the participating crewmen. The combined stresses of space flight include weightlessness, acceleration, confinement, restraint, long-term maintenance of high levels of performance, and possible desynchronosis. Endocrine measurements to assess the physiological cost of these stresses have been considered from two aspects. Fluid and electrolyte balance have been correlated with weight loss, changes in the excretion of aldosterone and vasopressin and fluid compartments. The second area involves the estimation of the physiological cost of maintaining a given level of performance during space flight by analysis of urinary catecholamines and cortisol. Inter-individual variability was demonstrated in most experimental indices measured; however, constant patterns have emerged which include: body weight change; increases in plasma renin activity; elevations in urinary catecholamines, ADH, aldosterone and cortisol concentrations. Plasma cortisol decreases in immediate postflight samples with subsequent increase in 24-hour urines. The measured changes are consistent with the prediction that a relative increase in thoracic blood volume upon transition to the zero-gravity environment is interpreted as a true volume expansion resulting in an osmotic diuresis. This diuresis in association with other factors ultimately results in a reduction in intravascular volume, leading to an increase in renin and a secondary aldosteronism. Once these compensatory mechanisms are effective in reestablishing positive water balance, the crewmen are considered to be essentially adapted to the null-gravity environment. Although the physiological cost of this adaptation must reflect the electrolyte deficit and perhaps other factors, it is assumed that the compensated state is adequate for the demands of the environment; however, this new homeostatic set is not believed to be without physiological cost and could, except with proper precautions, reduce the functional reserve of exposed individuals.     

Space motion sickness

Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3-5 days, and as revealed by the Skylab M131 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.     

Pathophysiology of motor functions in prolonged manned space flights.

The influence of weightlessness on different parts of the motor system have been studied in crew members of 140 and 175 days space flights. It has been shown that weightlessness affects all parts of the motor system including (i) the leg and trunk muscles, in which severe atonia, a decrease of strength and an increase of electromyographic cost of contraction have been observed, (ii) the proprioceptive elements and the spinal reflex mechanisms in which decreased thresholds accompanied by decreases of maximal amplitude of reflexes and disturbances in cross reflex mechanisms have been found. and (iii) the central mechanisms that control characteristics of postural and locomotor activities. The intensities and durations of disturbances of different parts of the motor system did not correlate to each other, but did correlate with prophylactic activity during space flight. The data suggest a different nature of disturbances caused by weightlessness in different parts of the motor system.     

ELITE-S2: the multifactorial movement analysis facility for the International Space Station

Experimental observations of adaptation processes of the motor control system to altered gravity conditions can provide useful elements to the investigations on the mechanisms underlying motor control of human subject. The microgravity environment obtained on orbital flights represents a unique experimental condition for the monitoring of motor adaptation. The research in motor control exploits the changes caused by microgravity on the overall sensorimotor process, due to the impairment of the sensory systems whose function depends upon the presence of the gravity vector. Motor control in microgravity has been investigated during parabolic flights and short-term space missions, in particular for analysis of movement-posture co-ordination when equilibrium is no longer a constraint. Analysis of long-term adaptation would also be very interesting, calling for long-term body motion observations during the process of complete motor adaptation to the weightlessness environment. ELITE-S2 is an innovative facility for quantitative human movement analysis in weightless conditions onboard the International Space Station (ISS). ELITE-S2 is being developed by the Italian Space Agency, ASI is to be delivering the flight models to NASA to be included in an expressed rack in US Lab Module in February 2004. First mission is currently planned for summer 2004 (increment 10 ULF 2 ISS).     

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones.     

Changes in the vestibular function during space flight

An analysis of observations and investigations carried out in space flight has shown that some cosmonauts and astronauts have experienced vestibular disorders during the transition to weightlessness. Vestibular-sensory disorders include: Spatial illusions (the feelings of falling down, being in an upside-down position, the sensations of rotation of the craft or the body) and vertigo occurring during the onset of the orbital flight and head movements; Feelings, similar to those experienced in response to Coriolis accelerations on the Earth, which occasionally develop in weightlessness during the spacecraft rotation upon abrupt head and body movements and restrained feet; Feelings "of the load on the vestibular analyser which is unlike any Earth-bound effects" upon abrupt head movements during the first hours of an orbital flight and "a prolonged movement" during the switch-off of thrusters in weightlessness. Vestibular-vegetative disorders comprise a complex of symptoms similar to those of motion sickness: loss of appetite, stomach awareness (12%), hypersalination, nausea (9.6%) and vomiting (4.8%). Soviet studies suggest that the vestibular tolerance to the flight effects depends on the natural stability and training to the cumulative effect of adequate vestibular stimuli. This has been used in the development of the system of vestibular selection. Changes in the vestibular function seem to play the major role in the development of motion sickness in weightlessness, extra-labyrinthine factors being contributory. The current hypotheses have not yet been adequately confirmed in experiments. A detailed physiological analysis allows the conclusion that the decisive factor in the development of motion sickness may be the disturbance of the function of analysers responsible for spatial orientation which take the form of sensory conflicts as well as an altered reactivity of the organism due to the hemodynamic rearrangement.     

Animals in biomedical space research

The use of experimental animals has been a major component of biomedical research progress. Using animals in space presents special problems, but also provides special opportunities. Rat and squirrel monkeys experiments have been planned in concert with human experiments to help answer fundamental questions concerning the effect of weightlessness on mammalian function. For the most part, these experiments focus on identified changes noted in humans during space flight. Utilizing space laboratory facilities, manipulative experiments can be completed while animals are still in orbit. Other experiments are designed to study changes in gravity receptor structure and function and the effect of weightlessness on early vertebrate development. Following these preliminary animals experiments on Spacelab Shuttle flights, longer term programs of animal investigation will be conducted on Space Station.     

Prolonged weightlessness and calcium loss in man

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.     

Otorhinolaryngological problems in medical support of space flights

At present the main trends among the most important problems of otorhinolaryngology in space medicine have become defined as vestibulology, audiology and clinical aspects (prophylaxis, diagnosis and treatment of ENT diseases in flight). The principal result of recent vestibular studies has probably been the establishment of an apparent relationship between the resistance of the vestibular system to adequate ground-based stimulation and tolerance to space flight. The findings of the studies formed the basis for the development of a new system of vestibular selection, as well as demonstrated the usefulness of special vestibular training of astronauts by active and passive methods. In audiology certain urgency is acquired by the problem of noise limitation in space cabins and auditory system reliability prediction for preserving a high work capability in crew members. The hemodynamic changes in weightlessness, as well as the possibility for allergic lesions, create conditions for distorted course of the ENT diseases and vaso-motor disorders. The prophylaxis of aspirations also deserves close attention since the possibilities of their onset increase in weightlessness. The rendering of immediate, timely aid will depend not only on the presence of the necessary medical equipment but also on the ability of the crew members to render the appropriate otorhinolaryngological aid.