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[Functional state of the posterior lobe of the neurohypophysis of rats exposed aboard the biosatellite "Cosmos-936" (according to the results of morphologic studies)].

A comparative evaluation on some morphological indices of functional state of the posterior neurohypophysis was performed in rats subjected to weightlessness and artificial gravitation for 18.5 days on board the biosatellite "Cosmos-936". The data of the investigation were compared to those obtained on the test animals used for terrestial series of the experiment where all the factors of space flight, except weightlessness were imitated. As the analysis of morphological data demonstrated, a prolonged effect of weightlessness results in a considerable decrease in the number of the neurosecretory cumulative corpuscles (Herring's bodies), in decreasing volume of nuclei and size of pituicytes. A suggestion is made on decreasing basal level of functional activity of the hypothalamo-hypophyseal neurosecretory system under the conditions of weightlessness. Administration of artificial gravitation (lg) levels partly the changes produced by weightlessness and ensure a higher level of functioning in the neurosecretory system.

Animals↗

Antipyrine pharmacokinetics in the tail-suspended rat model.

As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greater concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our study was to examine the effects of simulated weightlessness on the pharmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total of 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day-1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated weightlessness. In addition, clearance was elevated after 1 day of tail-suspension in the p.o. dosing group. Steady-state volume of distribution was not statistically different over the entire study period in either dosing group. Data from the present study suggest that brief periods of tail-suspension may markedly alter the pharmacokinetics of drugs in the rat and that more studies are required in models of weightlessness and actual space flight to understand the complex interaction between microgravity and hepatic metabolic activity.

Administration, Oral↗

Gravity as a biochemical determinant.

The existence of obvious morphological and physiological changes in living systems exposed to altered gravity immediately informs us that prior changes have taken place in the chemistry of exposed cells, tissues and organs. These changes include transients that return more or less promptly to the norm when the system is restored to the terrestrial g-field. For example, altered serum hormone and electrolyte levels in man, which appear to reflect successful adaptation to the conditions of orbital weightlessness, disappear shortly after return to Earth. Other changes--in mineral and protein constituents of the skeletal system in man, and cell wall composition in plants--are more persistent or even permanent. Hypogravitational departures from the norm include not only "weightlessness" as achieved in orbit, but also experimental modes of compensation, on the clinostat or by flotation. These techniques are useful in the study of hypogravity but cannot replace fully the weightless environment. Plant ethylene and peroxidase both increase under orbital, clinostat and/or flotation conditions whereas 3-phosphoglyceraldehyde-dehydrogenase increases under orbital but not clinostat conditions; cytochrome reductase and malic dehydrogenase levels are affected by the clinostat, but not by actual weightless conditions. How do the altered organismal biochemistries induced by the centrifuge and the clinostat relate to one another? Does gravity operate on living systems as a continuous variable from 0 to superterrestrial values, or do deviations from g(earth) generate non-uniform, discontinuous stress responses, irrespective of sign? In plants, measurements of wall lignin content and peroxidase activity yield opposite answers. Given the limited data so far available we will consider the meaning of these contradictions.

Adaptation, Physiological↗

Body fluid metabolism at actual and simulated microgravity.

Recent observations from space missions indicate that weightlessness does not induce an increase in diuresis and natriuresis in astronauts. Rather, both oral fluid and sodium intake as well as renal fluid and sodium output appear reduced compared with the preflight condition. In addition, influences of reduced energy intake may be more important for total body fluid content inflight than generally assumed. Decreases in plasma volume and observations of upper body edema formation inflight indicate, in addition, an increased extravasation as a result of the headward fluid shift in weightlessness. Current simulations models of microgravity for body fluid metabolism are valid for simulations of the central fluid shift occurring in microgravity. Since weightlessness appears to decrease central venous pressure and does not induce an increased renal fluid and sodium excretion, while simulations models have opposite effects, additional models to simulate adaptation of body fluid metabolism to weightlessness might be necessary.

Adaptation, Physiological↗

Muscle strength during bedrest with and without muscle exercise as a countermeasure.

Bedrest is known to be a useful experimental model for simulating weightlessness and studying its effects on human skeletal muscle activity. We therefore conducted a study in which 12 healthy male subjects underwent 28 days of continuous exposure to 6 degrees head-down bedrest. Our main objective was to test a set of preventive countermeasures for maintaining the stability of the human body. Of the subjects 6 performed deadlifts in the supine position for 30 to 45 min each day. The isometric actions were performed for 5-30 s at 90, 120 and 150 degrees knee angles and isokinetic training at speeds of 30 and 180 degrees.s-1. In vivo quadriceps muscle strength was measured under controlled experimental conditions with a commercial dynamometer. The hypothesis that intense daily isometric and isokinetic leg exercise and lower body negative pressure (LBNP) might serve to maintain muscle strength under conditions of weightlessness was tested. Of the subjects 6, who did not perform any exercise, served as the control population under conditions of simulated weightlessness. The results showed that a significant reduction (P < or = 0.0001) in the muscle force [-10.3 (SD 6.7%)] occurred in the control group whereas no significant changes were observed in the trained group [+3.9 (6.8%)]. From these studies we conclude that intense muscle training and LBNP constitute efficient countermeasures to compensate for the biomechanical effects of weightlessness on human lower limbs and to limit other factors such as cardiovascular deconditioning.

Adult↗

Caloric stimulation during short episodes of microgravity.

Caloric testing was performed during parabolic flight at the NASA Reduced Gravity Facility in Houston, Texas. Six test subjects were stimulated with continuous unilateral air insufflation (25 degrees R), in a manner similar to the experiments performed in the extended weightlessness of orbital flight during the SL1 and D1 Spacelab missions. Nystagmus response was recorded by electro-oculography and eye video image. It was the purpose of the experiments to re-examine the apparent discrepancy between the disappearance of caloric nystagmus during short episodes of weightlessness and the finding that caloric responses can be elicited during periods of extended weightlessness. The present results agree with those of earlier experiments in that a prompt reduction of caloric nystagmus occurs on transition from hypergravity (1.8 G) to weightlessness. The time constant of nystagmus decay was estimated to be approximately 2-3s, a value which cannot be explained by cupular mechanics. A central gating mechanism involving the labyrinthine canal and otolithic afferents is proposed for the observed modulation of caloric nystagmus.

Caloric Tests↗

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.

Aerospace Medicine↗

Future investigations onboard Soviet biosatellites of the Cosmos series.

Many rat experiments onboard Cosmos biosatellites have furnished information concerning the effects of weightlessness, artificial gravity, and ionizing radiation combined with weightlessness on structural and biochemical parameters of the animal body. The necessity to expand the scope of physiological investigations has led to the project of flight primate studies. It is planned to carry out the first primate experiments onboard the Cosmos biosatellite in 1982. At present investigations of weightlessness effects on the cardiovascular and vestibular systems, higher nervous activity, skeletal muscles and biorhythms of two rhesus monkeys are being developed and tested. It is also planned to conduct a study of weightlessness effects on embryogenesis of rats and bioenergetics of living systems onboard the same biosatellite. Further experiments onboard Cosmos biosatellites are planned.

Adaptation, Physiological↗

The first dedicated Life Sciences mission--Spacelab 4.

Spacelab is a large versatile laboratory carried in the bay of the Shuttle Orbiter. The first Spacelab mission dedicated entirely to Life Sciences is known as Spacelab 4. It is scheduled for launch in late 1985 and will remain aloft for seven days. This payload consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. An emphasis is placed on studying physiological changes that have been previously observed in manned space flight. This payload has complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. The experimental subjects include humans, squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The primary scientific objectives include study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Secondary scientific objectives include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs. The rationale behind this payload, the selection process, and details of the individual investigations are presented in this paper.

Adaptation, Physiological↗

The state of gravity sensors and peculiarities of plant growth during different gravitational loads.

In the primary roots of lettuce shoots grown under altered gravitational conditions--180 degrees inversion on the centrifuged clinostat, horizontal clinostat and in dynamic weightlessness--localization of the cellular organelles, cell morphology and peculiarities of growth have been studied. Significant changes took place in the localization of amyloplasts on the horizontal clinostat. The changes of amyloplast position in the cap cells on the horizontal clinostat and under weightlessness are similar. A change of the normal shoot position (180 degrees inversion and horizontal clinostat) causes an inhibition of growth. Weightlessness increases the length of axial organs and cells in the zone of elongation, but decreases the nitotic index in comparison to the centrifuged control. The anlysis of the formation of generative organs has been carried out for Arabidopsis plants grown on board the orbital station Salyut-6. The ability of plants to undergo vegetative growth and to pass through early phases of generative development under weightlessness was confirmed.

Arabidopsis↗

Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys.

Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

Animals↗

On the biological problems to be attacked with a series of U.S. satellites in 1966.

In the opinion of interested biologists in the U.S. the search for extraterrestrial life is by far the outstanding biological task that can be undertaken with the new technology of spacecraft. And it is their hope that the bulk of the national effort put into biology in space will be directed towards the biological exploration of Mars. There are, however, many other issues that the biologist can and should pursue in orbiting laboratories, or satellites. 1) Some of these are in the areas of the cardiovascular and neurophysiology of primates, and derive their importance from the need to put man into the weightless state for prolonged durations. 2) Other questions, similarly prompted by the prospect of prolonged space flight, concern the radiation hazard. Many experiments are planned for a single satellite in which it is hoped to discover whether the weightless state significantly affects biological responses to radiation. If, as is expected, there is no synergism between weightlessness and radiation, it will be possible to pursue all other questions about radiation effects in space by experimentation on the ground. 3) Two other classes of questions that satellite experiments may answer have deeper roots in theoretical and cellular physiology. The first of these concerns weightlessness itself. A long list of experiments involving a diversity of material from animal eggs to higher plants will seek to determine whether or not the absence of a gravitational input to the system significantly affects its general performance. Special interest in the U.S. attaches to suggestions from ground based experiments that normal morphogenesis may fail in plant systems that are exposed to less than about 10(-5) g. 4) It is also hoped that satellite experiments will help resolve the long-standing debate on the cause of persistent daily rhythmicity in organisms. One school of workers in the U.S. continues to believe that such rhythmicity is caused by organisms sensing an unidentified physical variable with a 24 hr period and hence presumably caused by the earth's rotation. It is proposed to assay the persistence and stability of such rhythms in organisms orbiting the earth with a period of about 90 min. Persistence of the rhythm in such orbital conditions would dispose of the theory of external causation; failure of such rhythms to persist would, however, constitute strong though not crucial support in its favor.

Animals↗

Acetylcholinesterase activity in soleus muscle intrafusal and extrafusal fibres in tail suspended rats.

Objective. To explore the mechanisms involved in muscle atrophy and conversion of the fiber types induced by simulated weightlessness. Method. Weightlessness was simulated by tail suspension of female rats. Intrafusal and extrafusal fibers of soleus muscles in the rat were examined histochemically for their activity of acetylcholinesterase (AChE) and succinic dehydrogenase (SDH) in 7 d, 14 d, 21 d tail-suspended groups and control groups. Result. Staining for succinic dehydrogenase showed that simulated weightlessness caused obvious atrophy and change in fiber type composition in soleus muscle, with decrease of the proportion of type I fiber and increase of type II fiber. Acetylcholinesterase activities of intrafusal and extrafusal fibers were both decreased significantly after 21 d tail suspension. Conclusion. Simulated weightlessness could induce decrease of AChE activity in neuromuscular junctions, which might be linked with decrease in motor neuron activity.

Acetylcholinesterase↗

[Detection of DNA variation after space flight in Datura innoxia by random amplified polymorphic DNA markers].

OBJECTIVE: To substantiate the effect of space environment on medicinal plants, the seeds of Datura innoxia were set up in retrievable satellites. METHODS: After returning to earth, the DNA variation of different groups was detected by random amplified polymorphic DNA (RAPD) markers. RESULTS: From a pre-screening of 65 primers with 20 oligonucleotide lengths, 15 primers that produced distinct profiles for each DNA sample were selected. In contrast with the earth controlled group, 39 polymorphic bands were produced in weightless group, and its degree of gene polymorphism was 23.1%; 45 polymophic bands were produced in hit group, and its degree of gene polymorphism was 24.4%. The polymorphic bands ranged approximately from 200 to 1990 bp. CONCLUSIONS: These results indicate that weightlessness induce DNA variation to some extents in Datura innoxia, while the compound effect of weightlessness and high energy heavy ions is more notable than the effect of single weightlessness.

Cosmic Radiation↗

[The effect of space flight conditions on the rate of multiplication, morphology of cells, DNA and protein content in the ciliate Tetrahymena pyriformis].

The conditions of a space flight and, in particular, the weightlessness promote an increased density of the ciliate culture, an enhanced reproduction rate, and an elevated ratio of dividing cells. The condition of weightlessness brings about some decrease in the bulk protein content of the cells determined by cytophotometry of Naphthol-yellow stained ciliates. The quantity of DNA in macronuclei was measured following the routine Feulgen procedure (its "cold" variant). The DNA content was found to remain unchanged. Some changes in the shape and size of the cells were noticed under flight conditions: ciliates that had developed in weightlessness appeared more spherical than control ones, due presumably to a decrease in the body length and to some extension in the body width. The conditions of space flight, including the weightlessness, induce changes in the physiological status of unicellular organisms. A decrease in the gravitation force may lead to a decrease in the energy expenditures for maintenance of the cell positional homeostasis.

Animals↗

[Interlabyrinthine asymmetry, vestibular dysfunction and space motion sickness].

The data available suggest that a disorder in the labyrinthine paired function can be regarded as a factor responsible for the initiation and development of space motion sickness. This concept is based on the assumption that in the norm the vestibular function is to a certain extent asymmetric which is made for by a compensatory center in the central nervous system. Exposure to an unusual space environment leads to a disorder of this compensation and development of a "new" vestibular asymmetry. This exposure involves: elimination of the difference in the weight of otolith membranes, disorder of the canal-otolith interaction, asymmetric blood-CSF changes, distinct interhemispheric asymmetry, general stress. Vestibular asymmetry that develops in the weightless state may become sufficient for the generalization of afferent impulsation to normal stimuli and development of a strong reaction. Adaptation to weightlessness occurs due to rearrangements of the compensatory center which are responsible for lower vestibular asymmetry. The compensatory mechanisms that have evolved in weightlessness continue to function during a certain time interval after recovery. They facilitate a re-initiation of vestibular asymmetry and motion sickness that is mainly provoked by head movements, as in the weightless state.

Ear, Inner↗

Spacelab mission 4--the first dedicated life sciences mission.

Spacelab is a large, versatile laboratory carried in the bay of the Shuttle Orbiter. The first Spacelab mission dedicated entirely to life sciences is Spacelab-4. It is scheduled for launch in late 1985 and will remain aloft for 7 d. All of the investigations are currently classified as "tentatively selected," with "final selection" and confirmation planned for late 1983. The 24 tentatively selected investigations have been combined into a comprehensive, integrated exploration of the effects of acute weightlessness as living systems. An emphasis is placed on studying physiological changes previously observed in manned space flight. This payload has complementary designs in both human and animal investigations in order to validate animal models of human physiology in weightlessness. The experimental subjects include humans, squirrel monkeys, laboratory rats, two species of plants, and frog eggs. The primary scientific objectives include study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness (including postflight reductions in orthostatic tolerance and exercise capacity), and changes in vestibular function (including space motion sickness), associated with weightlessness. Secondary scientific objectives include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and phototropism in plants, and fertilization and early development in frog eggs. The rationale behind this payload, the selection process, and details of the individual investigations are presented in this paper.

Animals↗

[Basic results of an experiment with mammals on the Kosmos-782 biosatellite].

The rat experiments carried out onboard the biosatellite Cosmos-782 contributed to our understanding of mechanisms of animal adaption to prolonged weightlessness. Postflight analysis helped to study nonspecific changes related to the stress-reaction accompanying space flight and return to the Earth gravity as well as specific changes associated with functional unloading of the musculoskeletal system in weightlessness. The flight results confirmed the previously made conclusions concerning possible adaptation of mammals to prolonged weightlessness and lack of pathological changes in vital weightlessness. They included: metabolic and hormonal changes, muscle atrophy, osteoporosis and delayed bone growth, decrease of ATPase activity of myocardial myosin, inhibition of erythropoiesis.

Adaptation, Physiological↗