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Mouse infection models for space flight immunology.

Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

Animals↗

[Radiation risk for astronauts during space flights on board the space station "MIR"].

Described is the algorithm for calculating the radiation risk to cosmonauts on orbital missions during different solar phases. The algorithm and the Fortran calculation program lie in the basis of presented radiation risk estimations for orbital manned missions of varying duration. The dependence of in-flight radiation risk on mission length, solar phase, and cosmonaut's age was analyzed. Magnitudes of radiation risk to cosmonauts were compared with the national demographic risk of male lethality over a similar period of time.

Algorithms↗

Fecundity and longevity of houseflies after space flight.

After 7 days of space flight house flies, Musca domestica, exhibited similar longevity, but a reduction in reproductive output as compared to earthbound controls. This reduction was not observed in later generations. These data suggest that space flight directly alters the rate of ovarian development, but that this effect is not genetically transmitted.

Animals↗

Planning strategies for development of effective exercise and nutrition countermeasures for long-duration space flight.

Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.

Cardiovascular Physiological Phenomena↗

Medical baseline data collection on bone and muscle change with space flight.

It has been documented that astronauts suffer from a progressive and continuous negative calcium balance in space flight. The National Space Development Agency of Japan (NASDA) discussed the experimental protocols with the National Aeronautics and Space Agency's (NASA's) Johnson Space Center (JSC) and has started a medical baseline collection on bone and calcium metabolism, and muscle changes with space flight. The subjects were two astronauts, a 42-year-old female and a 32-year-old male, who experienced real space flights. Fractional excretion of calcium (FECa) increased in both subjects just after the space flight. There was a negative calcium balance with urinary calcium leak even after a short flight. We also noticed a decrease (-3.0%) of bone mineral density (BMD) of the lumbar spine (L2-4), a weight bearing bone. These bone changes may be due to a negative calcium balance. However, the BMD of the skull, a nonweight bearing bone, increased after the flight. This indicates that the effect of weightlessness on bone is different in respective bones, depending on the weight loading. Our data of the bone metabolic marker clearly indicate that bone resorption is stimulated, shown by an elevation of urinary pyridinolinks and plasma tartrate-resistant acid phosphate (TRACP) activity. Bone specific alkaline phosphatase, a bone formation marker, was elevated in both subjects, but not intact osteocalcin. Whether this pathophysiological phenomenon is due to an accelerated bone resorption or suppressed bone formation is still obscure. In addition, the physiological cross-sectional area (PCSA) of muscle in the legs greatly decreased (from - 10% to -15%) after the flight, and it took over a month to be recovered in both subjects. However, the muscle volume loss in the legs seemed to be reversible. To examine bone and muscle metabolism with space flight, further investigations and international standardization of experimental protocols are necessary.

Adult↗

[Growth of wheat from seed-to-seed in space flight].

In our earlier space experiment with super dwarf wheat we found the spikes developed in space to be barren. The cause of the full crop sterility was sensitivity of this wheat species to the ethylene concentration of 0.3-0.8 mg/m3 during the experiment. The follow-up ground experiments were made to identify species of dwarf wheat that could be raised in space greenhouse Svet and are distinguished by partial tolerance of their reproductive organs to elevated ethylene in air. The choice fell on the USU-Apogee cultivar specially developed for planting in growth chambers as an integral part of various bioregenerative life support systems, including the space ones. An experiment with wheat Apogee was performed in greenhouse Svet on board MIR. The period of the full crop vegetation cycle was not significantly altered under the spaceflight conditions. The experiment yielded 508 seeds from 12 plants, i.e. by 38% less than in laboratory experiments and by 69% more as compared with results of growing crops in ethylene-contaminated atmosphere (1 mg/m3). Mass of the space seeds was low if compared with the laboratory crops. This was the first time when the feasibility of gathering seeds from wheat that had passed the whole vegetation cycle in space flight was demonstrated. The experiment will give mightly impetus to the advancement of research on space biological LSS and gravitational biology.

Air Pollutants↗

Comparing the effects of two in-flight aerobic exercise protocols on standing heart rates and VO(2peak) before and after space flight.

The effects of regular aerobic exercise on orthostatic tolerance have been the subject of a long-standing controversy that will influence the use of exercise during space flight. To examine these effects, astronauts performed continuous (CE) aerobic exercise (n = 8), interval (IE) aerobic exercise (n = 4), or no (NE) exercise (n = 5) during flights of 7 to 11 days. Heart rate (HR) responses to an orthostatic challenge (stand test) were measured 10 days before flight and on landing day. VO(2peak) (graded treadmill exercise) was measured 7 to 21 days before and 2 days after flight. No significant differences across the groups were observed in standing HRs before or after flight. However, the within-group mean HRs significantly increased in the NE (71-89 beats/min) and CE (60-85 beats/min) groups after space flight. The HRs for the IE group did not significantly increase (75-86 beats/min) after space flight. VO(2peak) decreased (P < .05) in the NE (-9.5%) group, but did not change in the CE (-2.4%) and IE (1%) groups. The relationship (r = 0.237) between the delta HR and delta VO(2peak) was not significant. These preliminary results indicate that: (1) continuous exercise does not affect the orthostatic HR response after space flight; (2) interval exercise may minimize an increase in the postflight orthostatic HR; and (3) both exercise protocols can maintain VO(2peak).

Adult↗

Space flight, microgravity, stress, and immune responses.

Exposure of animals and humans to space flight conditions has resulted in numerous alterations in immunological parameters. Decreases in lymphocyte blastogenesis, cytokine production, and natural killer cell activity have all been reported after space flight. Alterations in leukocyte subset distribution have also been reported after flight of humans and animals in space. The relative contribution of microgravity conditions and stress to the observed results has not been established. Antiorthostatic, hypokinetic, hypodynamic, suspension of rodents and chronic head-down tilt bed-rest of humans have been used to model effects of microgravity on immune responses. After use of these models, some effects of space flight on immune responses, such as decreases in cytokine function, were observed, but others, such as alterations in leukocyte subset distribution, were not observed. These results suggest that stresses that occur during space flight could combine with microgravity conditions in inducing the changes seen in immune responses after space flight. The biological/biomedical significance of space flight induced changes in immune parameters remains to be established. Grant Numbers: NCC2-859, NAG2-933.

Aerospace Medicine↗

Research on humans during space flights: ethical problems.

Experiments on humans during space flights call for ethical reflection, which is more than a mere assessment of the risks and a concurrent ethical evaluation of manned space flight as such. Although it may be desirable to harmonize ethical standards for international space flights especially against the background of the construction of an International Space Station (ISS) the application of ethical standards for human experiments on earth to the situation in space is not (at all) straight forward. The analysis shows that an ethical evaluation of experiments in space involving humans cannot be made solely on grounds of those principles which apply in comparable cases of terrestrial experiments. The very special conditions in space necessitate further ethical considerations. From this it may of course not be inferred that the current practice of strict ethical evaluation of experiments on humans becomes obsolete once we leave the planet earth. On the contrary, it means that widely accepted principles--like free and informed consent, or data protection and privacy--may need to be amended in order to take proper account of the special conditions in space and the need to achieve a consensus among the different persons involved.

Aerospace Medicine↗

Effects of space flight on endocrine system function in experimental animals.

The effects exposing rats to space flights of various lengths in a series of COSMOS satellites are reported based on an evaluation of plasma hormone levels and several enzyme activities in the tissues. The results after space flights are compared with those obtained from rats exposed to acute or repeated stress. Space flight induced selective morphological responses in the corticotrophs and gonadotrophs of the pituitary. Plasma levels of ACTH did not change, but plasma growth hormone and TSH levels decreased after longer space flights (>14 days), while prolactin in the plasma increased after short flights (5-7 days). Plasma corticosterone was higher after all flights. Catecholamine levels in plasma increased only after long space flights. These changes in plasma hormone levels affected the activities of enzymes involved in the amino acid metabolism of the liver and lipolysis in the adipose tissues. Norepinephrine level and catecholamine synthesizing enzyme activity in the hypothalamus did not change in flight rats. The norepinephrine content, however, decreased in several nuclei selected from the hypothalamus of flight rats. Increases in plasma insulin and glucose were noted in rats after space flight. Glucagone values in plasma remained unchanged. Comparing these results from flight rats against rats exposed to acute or repeated stress indicate that long stays in microgravity do not represent intensive stressogenic stimulus of the adrenocortical and sympathetic adrenomedullar systems, and hormone alterations observed after space flight may be due primarily to acute stressor activity resulting from a return to Earth's gravity (gravitational stress).

Adaptation, Physiological↗

Effect of space flight on the development of endocrine functions in rats.

The effects of the exposure to space flights on plasma hormone levels were studied in adult male rats, in pregnant females and in their progeny. An increase of plasma corticosterone (CS) and insulin (I) levels was found in male rats after space flights for a period of 7, 15, 18 and 20 days. Plasma levels of growth hormone (GH) were decreased and those of epinephrine (E) and norepinephrine (NE) were elevated in rats exposed to longer space flights (18 or 20 days). In pregnant female rats no significant changes of plasma concentrations of CS, GH, I, E and NE were noted after short term space flight (5 days). However, the plasma prolactin levels were elevated. In young animals exposed to space flight during fetal development no changes of plasma I and prolactin levels were noted during the period of postnatal growth. However, the plasma CS levels were elevated in these rats and no gradual increase of CS plasma concentration was observed during the postnatal period. The plasma GH levels were reduced in rats exposed to space flight and the levels of catecholamines in plasma and in adrenal glands were elevated in 30 and 100 day old rats exposed to microgravity during the fetal development. These results demonstrated: 1. that exposure of rats to space flight is followed by changes in I and CS plasma levels, but the sympathetic-adrenomedullary system is only slightly activated by longer space flights; 2. that a short term space flight is only a mild stressor for pregnant rats and slightly affects the activity of adrenocortical and sympathetic-adrenomedullary systems during the development of their offsprings.

Animals↗

Calcium utilization by quail embryos during activities preceding space flight and during embryogenesis in microgravity aboard the orbital space station MIR.

A series of studies were conducted to determine the effect of activities preceding spaceflight and during space-flight on calcium utilization during quail embryonic development. In the pre-space trials, fertile quail eggs were subjected to pre-flight dynamics including forces of centrifugation, vibration, or a combination of vibration and centrifugation prior to incubation for 6 or 16 days. Quail eggs were also tested for survivability in a refrigerator stowage kit for eggs (RSKE) which was subsequently used to transport the eggs to space. Eggs in the RSKE were subjected to shuttle launch dynamics including G force and random vibration profiles. The space-flight trial involved 48 quail eggs launched on space shuttle Flight STS-76 which were subsequently incubated in a Slovakian incubator onboard space station, MIR. Two ground control trials, each with 48 eggs with and without exposure to shuttle launch dynamics were initiated 5 days post-launch. Eggshells from all study trials were retrieved and analyzed for calcium content. Results showed that neither pre-flight activities nor shuttle launch dynamics had an effect on calcium utilization by developing embryos. However, calcium utilization by developing embryos incubated in microgravity was impaired by 12.6% when compared to embryos incubated on earth under laboratory control environment. This impairment was believed to be due to unidentified factors of the microgravity environment.

Animals↗

Space flight and neurovestibular adaptation.

Space flight represents a form of sensory stimulus rearrangement requiring modification of established terrestrial response patterns through central reinterpretation. Evidence of sensory reinterpretation is manifested as postflight modifications of eye/head coordination, locomotor patterns, postural control strategies, and illusory perceptions of self or surround motion in conjunction with head movements. Under normal preflight conditions, the head is stabilized during locomotion, but immediately postflight reduced head stability, coupled with inappropriate eye/head coordination, results in modifications of gait. Postflight postural control exhibits increased dependence on vision which compensates for inappropriate interpretation of otolith and proprioceptive inputs. Eye movements compensatory for perceived self motion, rather than actual head movements have been observed postflight. Overall, the in-flight adaptive modification of head stabilization strategies, changes in head/eye coordination, illusionary motion, and postural control are maladaptive for a return to the terrestrial environment.

Adaptation, Physiological↗

[Changes in the body weight of cosmonauts during a 140-day space flight].

During 140-day space flight body mass changes of the Commander and Flight-Engineer were measured. No correlation between body mass losses and flight duration was found. Greatest body mass losses occurred on MD 44--59 in Commander (2.3--2.4 kg), and on MD 86 in Flight-Engineer (5.4 kg). Later the losses decreased. The results suggest that body mass changes varied on an individual basis and depended on many spaceflight factors.

Body Weight↗

Graviperception in the flagellate Euglena gracilis during a shuttle space flight.

During a recent space flight, gravitaxis of the unicellular photosynthetic flagellate, Euglena gracilis, was studied on board of the American shuttle Columbia. Accelerations were varied between 0 and 1.5 x g using a slow rotating centrifuge microscope (NIZEMI). The cells showed a sigmoidal response curve for the dependence of the precision of gravitaxis on acceleration which is indicative of the involvement of an active, physiological gravireceptor with a threshold at g-values < or = 0.16 x g and a saturation at g-values > or = 1 x g. No adaptation to microgravity was found during the prolonged space mission. After return the cells showed a normal gravitactic behavior at 1 x g. Since the cells are heavier than water, their swimming velocity is affected by sedimentation. The velocity distribution at different accelerations closely follows Stokes' law for sedimentation indicating that, in contrast to the ciliate Paramecium, E. gracilis, does not show any gravikinesis.

Acceleration↗

[Characteristics of Triticum vulgare in the early phases of development (ontogenesis) in space flight].

The effect of space flight factors on the growth and development of wheat grown in a Svetoblock-M unit on the orbital station Mir was investigated. The data obtained allow the conclusion that wheat plants develop flight-induced changes. When compared to control plants, experimental plants show a delayed growth in terms of biometric parameters, different distribution of biogenic elements, lower phytoncidal activity, increased bacterial and fungal contamination, and a changed pigment and lipid composition.

Space Flight↗

Cardiovascular changes in prolonged space flights.

In prolonged manned space flights, the cardiovascular function was examined at rest and during provocative tests. As compared to the preflight data the following changes were seen: higher heart rate at rest and during LBNP tests, decrease of stroke volume at rest and during LBNP test and a less marked increase (or decrease) during exercise tests, symptoms of a greater heart load which transformed to the syndrome of myocardial hypodynamics (preload) during LBNP tests or to the syndrome of myocardial hyperdynamics (afterload) during exercise tests (with other than preflight ratios of systolic and diastolic time intervals). The above cardiovascular changes did not, as a rule, aggravate with flight time and can be viewed as adaptive reactions to microgravity. The above cardiovascular changes were primarily produced by fluid redistribution in the cranial direction, diminished participation of the muscle system in circulation, and involvement of unloading reflexes from the cardiopulmonary receptor zones.

Blood Pressure↗

[Variability of mycelial microorganisms in space flight].

The effect of space flight factors on the mycelial procaryotic (Streptomyces roseoflavus var. roseofungini) and eucaryotic (Fusarium bulbigenum var blasticola) microorganisms has been studied. Phenotypical changes were observed in all the strains studied. The ability to form secondary colonies decreased with reduction of the time interval between inoculation and spacecraft launch. The antimicrobial spectrum of Str. roseoflavus, a producer of an antifungal antibiotic, changed too.

Antifungal Agents↗