Vestibular function and space motion sickness

The vestibular system plays an important role in intersensory interactions and gravitation is a natural stimulus for its receptors. Weightlessness alters the input signals of the otoliths and their effect on the pattern and dynamics of changes in the vestibular function (VF), which is accompanied by development of space adaptation syndrome (SAS) and space motion sickness (SMS). These changes occur both during the spaceflight (SF) and after returning to Earth, but the mechanisms of their development are still poorly understood and require special studies. In total, 47 Russian cosmonauts (crewmembers of long-term International Space Station (ISS) missions) have participated in the studies into VF before and after SF and nine of them, in onboard studies during SF (129–215 days) as a part of the Virtual space experiment (stage 1). Electro- and video-oculography are used to record spontaneous eye movements (SpEM), static vestibular–ocular responses during head tilts to the right or left shoulder (static otolith–cervical–ocular reflex, OCOR), and dynamic vestibular-ocular response during the head rotation around the longitudinal axis of the body. The examination is accompanied by personal and questionnaire survey on subjective responses and complaints of cosmonauts about SAS and SMS. Significant changes in SpEM (drifts of eyes, spontaneous and gaze-evoked nystagmus, and arbitrary saccades) and a decrease in OCOR (statistically significant decrease in the amplitude of ocular counter-rolling in response to head tilts up to its absence or inversion, an atypical OCOR) are observed during SF. An atypical OCOR is observed at the beginning of adaptation to weightlessness in seven of the nine cosmonauts (the first one to two weeks of SF) and repeatedly throughout the flight in all cosmonauts regardless of whether it is their first flight or not. Atypical vestibular responses after SF, similar to the responses during SF, are observed in several cosmonauts by day 9 after flight. It has been shown that atypical OCOR variants are more frequently observed in the subjects lacking any previous space experience, as well as a more pronounced decrease in this response with a concurrent increase in the response of the semicircular canals. It is also demonstrated that repeated SFs lead to a considerable shortening in the after-flight readaptation to terrestrial conditions and a considerable decrease in the degree of vestibular disorders. In the initial period of SF, the changes in VF are correlated with the complaints and manifestations of SAS and SMS; however, the complaints and the corresponding symptoms are unobservable during the further flight despite significant changes in the VF state. The patterns of the VF disorders associated with the impact of weightlessness and observed during and after SF are very similar, allowing these disorders to be regarded as SAS and SMS of different severities (intensities).     

Alterations of characteristics of horizontal gaze fixation reaction in long-term space flights

The study was performed to explore effects of long-duration SF on the characteristics of horizontal gaze fixation reaction (hGFR). Changes in GFR observed in long-duration space flight (SF) point out to serious disturbances of the VOR system due to, apparently, altered vestibular activity. Two strategies of reaction adaptation to the microgravity conditions were discovered in cosmonauts of civic occupations and pilots.     

Calcium metabolism characteristics in microgravity]

The results of research of calcium exchange parameters at cosmonauts taken part in long space flights (SF) onboard of orbital stations "SALUT" and "MIR" within 1978-1998 were generalized. The analysis of data received during observation of 44 cosmonauts (18 of them have taken part in long SF twice) was done. The observation was carried out before and after SF by duration 30-438 days. The content of a total calcium in blood serum was increased basically by the increase of its ionized fraction after flights of moderate (3-6 months) and large duration (6-14 months) along with the significant increase of PTH and decrease of calcitonin levels. The content of osteocalcin after SF was increased. Three cosmonauts participated in research of calcium kinetics using stable isotopes before, in time and after a 115-day SF. Reduction of intestinal absorption, excretion through a gastrointestinal tract, and increase of calcium excretion with urine were marked in time of SF. In early postflight period a level of intestinal absorption, on the average, was much lower than in SF, and the calcium removal through intestine was increased. Both renal and intestinal excretion of calcium were not normalized in 3.5-4.5 months after end of SF. Increase of resorbtive processes in bone tissues which induced negative bone balance during flight was observed in all test subjects, proceeding from estimations of speed of the basic calcium flows made on the basis of mathematical modeling. The conclusion about decrease in speed of bone tissue remodeling and strengthening of its resorption proves to be true by data of research of biochemical and endocrine markers.     

Circadian rhythms of salivary cortisol content during long-term space flight

Adaptation mechanisms of adrenal function related to secretion of cortisol were studied under conditions of microgravity. Parameters of diurnal rhythms of salivary cortisol were studied by Russian cosmonauts on board orbital station Mir during long-term space flights (SF). The preflight circadian rhythms of salivary cortisol in cosmonauts were characterized by the morning maximum occurring at 9∶43 a.m., the fluctuation amplitude 6.05 nmol/1, and the daily average concentration 8.79 nmol/l. The characteristics of cortisol diurnal rhythm changed under conditions of long-term space flight. On average, the rhythm measure and amplitude decreased after two months of flight. The postflight maximum concentration of free cortisol tended to occur later in the day. Evidently, the motor activity during SF, i.e., prophylactic exercises along with other factors, significantly influenced the parameters of cortisol circadian rhythm that was revealed by the individual variability of findings during the flight. After the long-term SF, individual ratios of salivary and plasma cortisol levels increased against the background of increased plasma content of the hormone, i.e., the fraction of free, physiologically active hormone in the total pool of circulating molecules decreased.     

Vestibular Function after Repeated Space Flights

This paper presents the results from testing the vestibular function on return from repeated space flights (SF) in 32 cosmonauts of the International Space Station that were in long SFs of 125–215 days. The cosmonauts were tested twice before the flight (baseline data collection) and on days 1–2, 4–5, and 8–9 after landing. The testing was made using two methods for recording eye movements (with simultaneous recording of head movements): electro-oculography and video-oculography. It is shown that the repeated stay in the long SF leads to a considerable statistically significant reduction in the de-adaptation period. Atypical vestibular disorders and changed patterns of the otolith-semicircular canal interaction are observed mostly in the cosmonauts who have made their maiden flights to microgravity.     

Prediction of alterations in cardiac functions (ECG data) in the course of the permanent monitoring of cosmonauts starting from selection until return to earth after short space flights

Analysis of alterations in the cardiac activity on the basis of electrocardiographic (ECG) findings in 29 cosmonauts of flight and ground professions aged from 29 to 61 years after 34 short (8–30 days) space flights (SFs) between 1982 and 2006 has been carried out. The ECG data at the stage of clinical selection, clinical-physiological examination (CPE) before a SF, at the stage of the launch of a spacecraft (SC) into orbit and its landing on Earth and at the stage of postflight CPE have been analyzed. The analysis of cardiac activity parameters on the basis of ECG data at different stages of observations has led to the identification of three groups of cosmonauts. There were no significant changes or negative tendencies in the alteration of ECG data in the first group (55.2% of the total number of cosmonauts) during the observation period from selection to the end of the SF. The changes that later became more pronounced during the landing on Earth and were retained during postflight CPE have been found in the second group of cosmonauts (in 34.5% cases) at the time of selection and preflight CPE. Considerable disturbances in cardiac activity that are dangerous for human health have been found in ECGs in the third group (10.3%) during the descent from orbit. The data from the study are the first step in the investigation of possible medical risks for the development and improvement of requirements for the medical selection of crews and the admission of subjects with partial health insufficiency on SFs.     

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.     

Osteoclast-activating system in cosmonauts after long-term international space station missions

The results of studying the system of the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) in 22 Russian cosmonauts after long-term (124–199 days) International Space Station missions are presented. It was found that early readaptation period is associated with changes in the serum concentrations of OPG and RANKL and the production rate of OPG and RANKL in phytohemagglutinin (PHA)-stimulated and non-stimulated mononuclear cells of peripheral blood in vitro. The extent of these changes varied in different subjects. Our data suggest that the OPG/RANKL cytokine system takes part in the processes of bone remodeling in cosmonauts after long-term missions.     

24-hr blood pressure in HDT-bed rest and short-lasting space flight

In 2 ESA-cosmonauts we compared the 24-hr profiles in blood pressure (BP) and heart rate (HR) to those that we had observed in an earlier head-down tilted (HDT) bed rest study. In view of the lack of gravitational stress, an attenuated profile was expected, as in HDT. To obtain a full profile we measured automatic upper-arm cuff measurements in 2 cosmonauts, combined with PortapresTM recordings in one. Unlike HDT, actual microgravity did not result in attenuated circadian profiles. The levels of systolic and diastolic pressures tended to be slightly lower in flight. Only nighttime heart rate was significantly lower in Space.     

Antibodies to muscle fiber antigens in the cosmonauts after a space flight]

The study of serum samples, obtained from 15 cosmonauts before and after space flights, with the use of the indirect fluorescent method showed that in 7 cosmonauts antibodies to different elements of the human heart muscle appeared after flights. Strong and very strong luminescence of the elements of heart muscle tissue was detected in the cosmonauts after the third space flight. When studying the sera on sections of bovine heart muscle tissue, the reactions of the sera taken before and after flights were found to have no essential differences.     

Cytogenetic studies of blood lymphocytes of cosmonauts after long-ter, space flights

An analysis was performed of unstable chromosomal aberrations in peripheral blood of 36 cosmonauts after long-term space missions on "Mir" orbital station. 25 cosmonauts were examined before their flights to score spontaneous yields of cytogenetical damage. In all cases the doses absorbed by crews during space flights did not exceed permissible levels of irradiation, adopted for cosmonauts. The frequencies of chromosomal-type aberrations after space missions were found to increase significantly compared to the pre-flight levels. The yields of dicentrics and centric rings on the average were as high as 0.12 +/- 0.02 and 0.47 +/- 0.06% before and after the 1st flight, 0.18 +/- 0.05 and 0.71 +/- 0.11% before and after the 2nd flight respectively. During the inter-flight periods, usually lasted 1.5-2 years, the yields of chromosome damage lowered, but did not reach their spontaneous values. After each next flight the yields of chromosome aberrations increased again. The cytogenetical damage detected in cosmonauts' peripheral blood lymphocytes after chronic action of low doses of space radiation points out a possible increase in risks of stochastic effects in distant future for crews after long-term space missions.     

Dynamics of the body liquids and composition in long-duration space flight (Bioimpedance Analysis)

Bioimpedance measurement was used to study dynamics of human hydration status and body composition on board the International space station (ISS). At different stages of 100- to 200-day flights of 12 cosmonauts, the volume of their body liquid was reduced: the overall, intra-, and extracellular volumes became on average 5.2 to 10.4% less per group as compared to the baseline level. The in-flight changes in the body composition of the cosmonauts were also consistent: while the lean mass loss determined by impedance measurement was insignificant (on average, from 1.9 to 4.0%), the gain of the fatty mass ranged from 4.6 to 8.2% during the first three months of the flight. Thus, hydration of a human body decreased during the long-term space flight, which was accompanied by reduction of the muscular mass and the gain in fatty mass.     

Parameters of the innate and adaptive immunity in cosmonauts after long-term space flight on board the international space station

The results of the study of the innate and adaptive immunity indicators in 12 cosmonauts who took part in long-term (128–215 days) expeditions on board the International Space Station (ISS) are presented. It was shown that the space flight may lead to deviations in the human immune system. A decrease in the functional activity of phagocytes, NK and T-cells, as well as in the ability of immunocompetent cells to synthesize cytokines were observed. Significant individual changes were observed in the immune system’s response to a long-term space flight, which indicated an individual’s predisposition to the development of immune reactivity disorders under varying gravitation conditions.     

The volume of extracellular fluid under conditions of long-term space flights

The volume of extracellular fluid (the bromine space) was determined in 18 cosmonauts 30 days before the start of a space flight and on the first day after landing. The duration of space flights on the Mir orbital station was from 126 to 438 days. Moreover, the volume of extracellular fluid was determined in seven cosmonauts directly during long-term space flights approximately two weeks before landing. After long-term space flights, the volume of extracellular fluid was decreased in all cosmonauts studied. The bromine space volume was significantly decreased compared to its initial preflight value. A decrease in the volume of extracellular fluid was caused not only by the reduction in the dense mass of the body but also by its dehydration. These processes developed independently of the duration of weightlessness but are mainly determined by the individual features of human beings.     

Some changes of the heart bioelectric activity at the cosmonauts under the influence of LBNP in the long duration flights

There was selected the group of the cosmonauts, who carry out long duration flights on the orbital complex "Mir", in which the tolerance of LBNP test was evaluated as poor (by hemodynamic indices--heart rate, arterial pressure, rheoencephalographic indices). The in-depth analysis of the electrocardiogram (in DS leads) indices was carry oiled on possible disturbances of conductivity and dynamics of temporary or amplitude characteristics. Furthermore is carry oiled the comparative estimation of these indices with the results of ECG analysis at the cosmonauts, who tolerance test good. Studies showed that the most informative ECG indices are the R, T-amplitudes and QT-interval. Under the influence of LBNP, especially during rarefactions on 45 and 50 mm Hg was noted reduction in the R, T-amplitude and the relative extension of QT-interval. The directivity of changes in these indices are identical for the cosmonauts with good and poor tolerance of the test; however in flight manifestation of the changes is more significant for the cosmonauts with poor tolerance of LBNP test. Thus, in the formation of orthostatic stability together with the hemodynamic influences take part the bioelectric processes, which are formed in the myocardium.     

Cluster analysis in the fitness evaluation of cosmonauts during long-term missions on board the International Space Station

Cluster analysis of the following parameters was performed in 13 cosmonauts: the duration (min), amount (m), and speed (km/h) of physical locomotor exercise (PLE) including running, and total locomotion (running + walking). These activities were the part of the program of long-term missions on board the International Space Station. The cosmonauts were divided into three groups, which included two, five, and six subjects, respectively. The parameters of the PLE amount and speed significantly increased (p < 0.03) when going from the first to the third group. There was no significant difference in the duration of PLE between the groups (p < 0.125). It is concluded that cluster analysis is an appropriate method for fitness evaluation of cosmonauts during long-term space flights.     

Some aspects of the comparative analysis of hemodynamic responses to LBNP tests in cosmonauts of different age groups

The age-specific indicators of the functions of the cardiovascular system and its responses to the lower body negative pressure (LBNP) test were studied in career cosmonauts for the first time. The results of 174 LBNP tests implemented within the standard medical monitoring program on board the ??Mir?? orbital station (OS ??Mir??), using a Gamma-01 device, and aboard the International Space Station (ISS), using the Gamma-1M complex, were subjected to comparative analysis. In total, 38 cosmonauts from 25 long-duration space missions on board the ??Mir?? OS and ISS, who were examined in their pre-flight state and during in-flight periods, beginning, typically, on flight day (FD) 120, were subdivided into two age groups: 30- to 39-year-olds (their mean age was 36 ± 0.7 years; 39% of the total number of subjects) and 40- to 55-year olds (their mean age was 46 ± 0.8 years; 61% of the total number of subjects). We have revealed age-specific indicators for the hemodynamic status recorded at each stage of the investigation: at rest in a preflight state; responses of the indicators to the effects of microgravity; the relative dynamics of the indicators due to a simulated orthostatic posture, which was unidirectional but substantially different at the pre-and in-flight stages. For purposes of medical control, our results have shown that we need to establish age-specific references in our methodical approaches to the analysis and interpretation of the data received from monitoring cosmonauts?? health in their preflight state and during the entire mission and, which is particularly important in practical terms, when evaluating the LBNP test intolerance at different flight stages.     

Fitness facilitates sleep

Eight army recruits were studied at the start, middle, and end of their initial 18-week training programme. At each point the subjects were studied for four consecutive nights in the sleep laboratory. Their sleep was characterized by the means of the recordings on the last two nights. Within 2 days of the sleep recordings (but never on the same day) each subject spent 2 non-consecutive days in the exercise laboratory. On the 1st day a maximum oxygen consumption (VO2 max) measurement was performed on a treadmill and on the 2nd day a 24-min progressive exercise bicycle ergometer test was carried out with simultaneous venous sampling (for lactic acid measurements) and oxygen consumption recordings from which the lactate turn point (LTP) was calculated. LTP was used as a measure of fitness. Approximately 1 week after the above measures lean muscle mass as calculated by total body potassium estimation was obtained for each subject. Slow wave sleep (SWS) as a percentage of total sleep time increased significantly between the start and the measurements at 9 and 18 weeks, being 21.9%, 29.9%, and 28.5% respectively. Anaerobic threshold increased significantly (P less than 0.05) over the first 9 weeks and continued to increase to the end of the training period (P less than 0.001) using VO2 when lactate level was 2 mmol/l as a percentage of VO2 max. With increase in fitness, sleep onset latency and wake time during sleep decreased and sleep efficiency improved. The results suggest that as fitness increases sleep quality improves.     

Effect of space flight factors on health of cosmonauts in the near and late term after space flights

Cytogenetical studies of cosmonauts' peripheral blood lymphocytes after space flights on MIR orbital station showed a statistically significant increase in the yields of radiation-induced chromosomal aberrations. However, similar studies with in vitro irradiation of biological objects with accelerated charged particles are of great importance for elucidation of the nature of cytogenetical damage induced in vivo. It is also important to investigate the structure of cosmonatus' diseases over their life, in particular, lens opacities and oncological diseases. Thus, the purpose of the investigations planned is to study cytogenetical damage in blood lymphocytes from cosmonauts after space flights on the ISS in vivo, as well as in donor blood lymphocytes after in vitro exposure to accelerated charged particles. The tasks of the project are as follows: determination of the yields and types of chromosomal aberrations in cosmonauts' blood lymphocytes before and after space flights, comparative studies of biological effects induced in vitro by different types of ionizing radiation in human blood lymphocytes in ground experiments, assessment of cytogenetical risks, analysis of the structure of cosmonatus' diseases comparing with that of whole population, study of the mortality and frequency of cataracts and oncological diseases in cosmonauts. The results to be obtained will be used for setting of health norms applied to the influence of radiations of different types, and for elaboration of measures to reduce health risks from space flight factors.