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.     

Serotonin in individual hypothalamic nuclei of rats after space flight on biosatellite Cosmos 1129.

The experiment on Cosmos 1129 was based on our results obtained in rats exposed to single or repeated restrain stress in the laboratory. These results have convincingly demonstrated a significant increase of serotonin concentration (5-HT) in the hypothalamus in acutely stressed rats. This response, which was found also in the isolated hypothalamic nuclei, was diminished in repeatedly (40 times) immobilized rats. While the concentration of 5-HT was unchanged in the majority of the hypothalamic nuclei of animals subjected to cosmic flight, an increase was recorded only in the supraoptic nucleus (NSO) and a decrease in the periventricular nucleus. These findings demonstrate that only few areas of the hypothalamus respond to cosmic flight with changes of 5-HT concentration and suggest either that long-term cosmic flight cannot be an intensive stressor or that during the flight the rats became already adapted to its long-term effect. However, the exposure of flight rats to repeated immobilization stress resulted in a significant increase of 5-HT in the NSO, para-ventricular and dorsomedial (NDM) nuclei. It should be noted that we have never seen any changes of 5-HT concentration, tryptophan hydroxylase and monoamineoxidase activities in repeatedly (40 times) immobilized rats. On the other hand, the increase of 5-HT concentration in the NDM is a typical finding after seven exposures of rats to immobilization on Earth, daily for 150 min. In the experiment COSMOS 1129 such an increase of 5-HT concentration in the NDM was found not only in the flight group but also in the control group of rats subjected to five daily exposures of immobilization stress. With respect to these findings, the increased 5-HT concentrations observed in some isolated hypothalamic nuclei in the flight group of rats exposed after landing to repeated immobilization stress suggest that long-term space flight and the state of weightlessness do not represent a stressogenic factor with respect to the serotoninergic system in the hypothalamus.     

Biomedical aspects of artificial gravity.

Artificial gravitv generated by spacecraft rotation may prove a universal countermeasure against adverse effects of weightlessness in the future. The paper summarizes the results of ground-based biomedical investigations of artificial gravity and flight experiments aboard Soviet biosatellites Cosmos-782 and Cosmos-936. It is believed that at the present stage the major goal of such investigations is to determine the minimum efficient value of artificial gravity in long-term flights which may eliminate adverse effects of prolonged weightlessness. In ground-bound studies the highest priority should be given to the development of methods on increasing human tolerance to the rotating environment.     

Metabolic changes in the animals subjected to space flight

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.     

Plasma and urine catecholamine levels in cosmonauts during long-term stay on Space Station Salyut-7.

The activity of the sympathetic adrenal system in cosmonauts exposed to a stay in space lasting for about half a year has so far been studied only by measuring catecholamine levels in plasma and urine samples taken before space flight and after landing. The device "Plasma 01", specially designed for collecting and processing venous blood from subjects during space flight on board the station Salyut-7 rendered it possible for the first time to collect and freeze samples of blood from cosmonauts in the course of a long-term 237-day space flight. A physician-cosmonaut collected samples of blood and urine from two cosmonauts over the period of days 217-219 of their stay in space. The samples were transported to Earth frozen. As indicators of the sympathetic adrenal system activity, plasma and urine concentrations of epinephrine and norepinephrine as well as urine levels of the catecholamine metabolites metanephrine, normetanephrine, and vanillylmandelic acid were determined before, during and after space flight. On days 217-219 of space flight plasma epinephrine and norepinephrine levels were slightly increased, yet not substantially different from normal. During stress situations plasma norepinephrine and epinephrine levels usually exhibit a manifold increase. On days 217-219 of space flight norepinephrine and epinephrine levels in urine were comparable with pre-flight values and the levels of their metabolites were even significantly decreased. All the parameters studied, particularly plasma norepinephrine as well as urine norepinephrine, normetanephrine, and vanillylmandelic acid, reached the highest values 8 days after landing. The results obtained suggest that, in the period of days 217-219 of the cosmonauts stay in space in the state of weightlessness, the sympathetic adrenal system is either not activated at all or there is but a slight activation induced by specific activities of the cosmonauts, whereas in the process of re-adaptation after space flight on Earth this system is considerably more markedly activated.     

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.     

Study of physiological effects of weightlessness and artificial gravity in the flight of the biosatellite Cosmos-936.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.     

The role of HZE particles in space flight: results from spaceflight and ground-based experiments.

Selected results from experiments investigating the potentially specific radiobiological importance of the cosmic HZE (= high Z, energetic) particles are discussed. Results from the Biostack space flight experiments, which were designed to meet the experimental requirements imposed by the microdosimetric nature of this radiation field, clearly indicate the existence of radiation mechanisms which become effective only at higher values of LET (linear energy transfer). Accelerator irradiation studies are reviewed which conform with this conjecture. The recently discovered production of "micro-lesions" in mammalian tissues by single HZE particles is possibly the most direct evidence. Open questions concerning the establishment of radiation standards for manned spaceflight, such as late effects, interaction with flight dynamic parameters, and weightlessness, are indicated.     

Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus

In long term space flight, the mechanical forces applied to the skeleton are substantially reduced and are altered in character. This reduced skeletal loading results in a reduction in bone mass. Exercise techniques currently used in space can maintain muscle mass but the mechanical stimulus provided by this exercise does not prevent bone loss. By applying an external impulsive load for a short period each day, which is intended to mimic the heel strike transient, to the lower limb of an astronaut during a long term space flight (5 months), this study tests the hypothesis that the bone cells can be activated by an appropriate external mechanical stimulus to maintain bone mass throughout prolonged periods of weightlessness. A mechanical loading device was developed to produce a loading of the os-calcis similar to that observed during the heel strike transient. The device is activated by the astronaut to provide a transient load to the heel of one leg whilst providing an equivalent exercising load to the other leg. During the EUROMIR95 mission on the MIR space station, an astronaut used this device for a short period daily throughout the duration of the mission. Pre- and post-flight measurements of bone mineral density (BMD) of the os-calcis and femoral neck of the astronaut were made to determine the efficacy of the device in preventing loss of bone mineral during the mission. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical stimulation does not produce a positive effect.     

Biochemical and morphological stress-reactions in humans and animals in microgravity

This article is a literary review focused on the problem of the stress-effect of microgravity. Based on the all-round analysis of data from manned missions and space experiments with rats it is concluded that microgravity as a permanent factor of space flight does not produce an intense chronic stress in either humans or animals. On the other hand, microgravity is responsible for deconditioning of a number of vital systems and of the organism as a whole. On return to Earth, the deconditioned bodies of humans and animals exaggerate the usual terrestrial loads due to gravity forces and respond by acute gravitational stress.     

Summary of experiments onboard Soviet biosatellites.

Physiological, morphological and biochemical studies of mammals flown onboard biosatellites of the series Cosmos revealed changes in their cardiovascular, musculoskeletal, endocrine and vestibular systems. Space flight resulted in moderate stress reactions, intralabyrinthine conflict information during movements and changes in fluid-electrolyte metabolism. Exposure to artificial gravity (1 g) decreased the level of myocardial, musculoskeletal and excretory changes, but disturbed the function of equilibrium. Studies with combined weightlessness and ionizing radiation demonstrated that weightlessness did not produce a significant modifying effect on radiation damage and postradiation recovery. Consistent changes in certain systems of animals and humans in weightlessness confirm the practical importance of biosatellite studies, which also contribute to the solution of general biology, problems associated with gravity effects on life processes.     

Biomedical problems of EVA support during manned space flight to Mars

Current projects of manned missions to Mars are aimed to their realization in the second-third decades of this century. The purpose of this paper is to determine and review the main biomedical problems, that require a first and foremost decision for safety support of extravehicular activity (EVA) carried out by crewmembers of the Mars expedition. To a number of such problems the authors of the paper attribute a creation of adequate EVA equipment intended, first, for assembly of interplanetary spacecraft on the Earth orbit, performance of maintenance operations and scientific researches on the external surface of spacecraft during interplanetary flight and, secondly, for work on the Mars surface. New generation of space suits with low weight, high mobility and acceptable risk of decompression sickness must be as a central component of EVA equipment. The program for preparation to a Mars expedition also has to include special investigations in order to design the means and methods for a reliable protection of crew against space radiation, to elaborate the approach to medical monitoring and primary medical care during autonomous space mission, to maintain good health condition of crewmembers during EVA under the Mars gravity (0.38 g) after super long-term flight in weightlessness.     

Autonomic regulation of circulation and cardiac contractility during a 14-month space flight

The space flight of physician cosmonaut V.V. Polyakov, the longest to date (438 days), has yielded new data about human adaptation to long-term weightlessness. Autonomic regulation of circulation and cardiac contractility were evaluated in three experiments entitled Pulstrans, Night, and Holter. In the Pulstrans experiment electrocardiographic (ECG), ballistocardiographic (BCG), seismocardiographic (SCG), and some other parameters were recorded. In the Night experiment, only the ballistocardiogram was recorded, but a special feature of this experiment is that the BCG records were obtained with a contactless method. This method has several advantages, the most important of which are the possibility of studying slow-wave variations in physiologic parameters (ultradian rhythms) on the basis of recordings made under standard conditions over a prolonged period. The Holter experiment (24-hour electrocardiographic monitoring) used a portable cardiorecorder (Spacelab, USA). The obtained electrocardiographic data were used to analyze heart rate variability. In the first 6 months of the 14-month flight, the dynamics of cardiovascular parameters in V.V. Polyakov was virtually the same as in the other cosmonauts. The data obtained after the first 6 months of Polyakov's sojourn in space are unique and mention should be made of at least three important aspects: (1) activation of a new, additional adaptive mechanism in the 8th-9th months of flight, as is evidenced by alterations in the periodicity and power of superslow wave oscillations (ultradian rhythms) reflecting the activity of the subcortical cardiovascular centers and of the higher levels of autonomic regulation; (2) growth of cardiac contractility accompanied by a decrease in heart rate during the last few months of flight; (3) a considerable increase in the daily average values of absolute power of heart rate's variability MF component, which reflects the activity of the vasomotor center. Specific mechanisms of adaptation to weightless conditions appear to be associated with activation of higher autonomic centers. The hypothesis that central levels of circulation regulation are activated in a long-term space flight was investigated by analyzing of ultradian rhythms in nighttime. The data, received during the flight of V. V. Polyakov, show, that the process of human adaptation to long influence of weightlessness consists of a number of consecutive stages, during which the activation of more and more high levels of control system of physiological functions occurs.     

A review of muscle atrophy in microgravity and during prolonged bed rest

With the prospect of long duration space missions in Earth orbit or to Mars, there is a need for adequate information on the physiological adaptations that will occur. One consequence of prolonged exposure to microgravity is muscle atrophy (loss of muscle mass). After a long duration space flight, muscle atrophy along with skeletal calcium loss would affect the capacity of astronauts to re-adapt to gravity on return to Earth. Of importance are any countermeasures which can attenuate the adaptive responses to microgravity. Experimentation is difficult in space with small subject numbers and mission constraints. Prolonged bed rest using healthy volunteers is used as an Earth-based model to simulate the muscle atrophy which occurs in the microgravity environment.     

Adaptation of neuromuscular activation patterns during treadmill walking after long-duration space flight

The precise neuromuscular control needed for optimal locomotion, particularly around heel strike and toe off, is known to he compromised after short duration (8- to 15-day) space flight. We hypothesized here that longer exposure to weightlessness would result in maladaptive neuromuscular activation during postflight treadmill walking. We also hypothesized that space flight would affect the ability of the sensory-motor control system to generate adaptive neuromuscular activation patterns in response to changes in visual target distance during postflight treadmill walking. Seven crewmembers, who completed 3- to 6-month missions, walked on a motorized treadmill while visually fixating on a target placed 30 cm (NEAR) or 2 m (FAR) from the subject's eyes. Electronic foot switch data and surface electromyography were collected from selected muscles of the right lower limb. Results indicate that the phasic features of neuromuscular activation were moderately affected and the relative amplitude of activity in the tibialis anterior and rectus femoris around toe off changed after space flight. Changes also were evident after space flight in how these muscles adapted to the shift in visual target distance.     

The endocrine system in space flight

Hormones are important effectors of the body's response to microgravity in the areas of fluid and electrolyte metabolism, erythropoiesis, and calcium metabolism. For many years antidiuretic hormone, cortisol and aldosterone have been considered the hormones most important for regulation of body fluid volume and blood levels of electrolytes, but they cannot account totally for losses of fluid and electrolytes during space flight. We have now measured atrial natriuretic factor (ANF), a hormone recently shown to regulate sodium and water excretion, in blood specimens obtained during flight. After 30 or 42 h of weightlessness, mean ANF was elevated. After 175 or 180 h, ANF had decreased by 59%, and it changed little between that time and soon after landing. There is probably an increase in ANF early inflight associated with the fluid shift, followed by a compensatory decrease in blood volume. Increased renal blood flow may cause the later ANF decrease. Erythropoietin (Ep), a hormone involved in the control of red blood cell production, was measured in blood samples taken during the first Spacelab mission and was significantly decreased on the second day of flight, suggesting also an increase in renal blood flow. Spacelab-2 investigators report that the active vitamin D metabolite 1 alpha, 25-dihydroxyvitamin D3 increased early in the flight, indicating that a stimulus for increased bone resorption occurs by 30 h after launch.     

Vestibular factors influencing the biomedical support of humans in space

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.     

On the contribution of space medicine in the public health care

With the beginning of space era, a new branch of medicine has arisen and has been developing along with human exploration of outer space. And even though space medicine mainly faces the same problems as traditional medicine--cosmonauts health care and their high efficiency--this branch, has its own features, associated with the unusual factors of space flight, of which weightlessness is the major one. During the development of manned cosmonautics (duration of a human stay in space has reached already 438 days), methods of cosmonauts medical support and monitoring of their condition have been developed, knowledge of human possibilities and methods of process of organism adaptation to various and frequently severe conditions of external environment have increased. All this led to the fact that nowadays space medicine can become useful for improvement of human health care not only in space but also on the Earth. Moreover, the problem of implementation of cosmonautics achievements, and in particular of space medicine, in practice of public health care presents one of the most important issues concerning human health care. It is also connected with public opinion which is more and more concerned about the efficiency of significant expenses on space activities, especially lately. People often are set by the questions: what has space given, what fruits has space research provided to mankind, which results of this research can be used on the Earth already today for improvement of their life, for discussion of many difficult earthly problems? In terms of using cosmonautics possibilities, its achievements for health care and treatment, it is possible to define a few branches, in which purposeful studies are carried out.     

Reflection Model as Applied for the Analysis of Enhancements of Solar Cosmic Rays at Different Heliocentric Distances: An Example of the Event Observed in June 1991 onboard GRANAT and ULYSSES Spacecraft

In this paper we consider a large-scale enhancement of the intensity of solar protons (E = 1–20 MeV) observed in June 1991 for 26 days at different points of interplanetary space, onboard ULYSSES (in the time period under consideration it was located at a heliocentric distance of 3 AU, at an angular distance of 70° to the East of the Sun–Earth line and 3° to the South of the ecliptic plane) and GRANAT (which was orbiting around the Earth spending most of its flight time outside the Earth's magnetosphere). An approximation is made of the complex time profile of the enhancement of the solar cosmic ray (SCR) intensity on the basis of the reflection model of their propagation in the heliosphere. It has been established that, in this event, the transport of SCR particles in the interplanetary space was mainly carried out in the traps made up by the fronts of radially moving flare disturbances. The parameters of these fronts obtained when modeling this enhancement of SCR allow one to estimate the characteristic dimensions of the regions of effective capture of SCR. Comparison of the results of approximations obtained for the data from GRANAT and ULYSSES spacecraft demonstrated an increase in the regions of capture of SCR when the radial distance from the Sun increases.     

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.