Analysis and Evaluation of the Functional State of the Cardiovascular System in Cosmonauts during Long-term Spaceflights

Forty-four cosmonauts participating in 28 main long-term (73–438 days) missions on the Mirorbital station performed functional tests with graded physical exercise using a bicycle ergometer. There were two types of this functional load. The cosmonauts that participated in the first eight main missions performed a two-step exercise with a total load power of 1150 W. In the remaining cosmonauts, the exercise was three-step, with a total power of 1350 W. The results obtained during the flight were compared with the results of the same tests performed before the flight, which served as control values for each cosmonaut. To estimate the load tolerance, the heart rate (HR), systolic blood pressure, stroke volume (SV), cardiac output (CO), and cardiac index were analyzed. The data were grouped according to the load, taking into account the type of blood circulation for each group before and during the flight. The ratio between different types of blood circulation was found to change during the flight. The responses to both types of exercises before the flight were less favorable in the cases of the hyperkinetic type of circulation. In these cases, the dominance of the chronotropic function of the heart determined the increase in CO. In the cases of the hypo- and eukinetic types of circulation, the response to the exercise was close to normotonic. In microgravity, irrespective of the circulation type and the exercise, the mechanism of the CO formation changed: the effect of HR was dominant, and there was no increase in SV. Insufficient venous return to the chambers of the heart is the main cause of the decreased response of SV to exercises during spaceflight.     

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.     

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.     

Changes in hemodynamic and post-flights orthostatic tolerance of cosmonauts under application of the preventive device--thigh cuffs bracelets in short-term flights

Specific aims: to evaluate the influence of the use thigh cuffs "Bracelet" on the hemodynamic adaptation to microgravity during short-term (up to a month) space flights, in-flight tolerance to LBNP-tests and post-flight orthostatic tolerance. 6 cosmonauts applied and 7 others did not apply the occlusive cuffs when on flight. The "Bracelet" device notably relieved the cosmonauts from the subjective discomfort following by the blood redistribution at initial period of exposure to microgravity. It was established that "Bracelet" lessened shifts in central and peripheral hemodynamics typical for exposure to microgravity, venous stasis in the cervical-cephalic region in particular. There were no differences between the hemodynamic reaction on LBNP-test in cosmonauts who applied and not applied "Bracelet" during short-term flights. The objective data are received, that the application of the device during short-term space flight does not make negative effects on post-flight orthostatic tolerance.     

Mechanisms of changes in human hemodynamics under the conditions of microgravity and prognosis of postflight orthostatic stability

The mechanisms of hemodynamic responses to orthostatic stresses and orthostatic stability (OS) of cosmonauts were studied before and after short-and long-term spaceflights (SFs) using orthostatic tests, as well as before, during, and after SFs using ultrasonic methods in tests with exposure to lower body negative pressure (LBNP). The capacitance and distensibility of the veins of the lower extremities were studied using occlusive air plethysmography before, during, and after SFs of different durations. A stay in microgravity has been proved to result in detraining of, mainly, the vascular mechanisms of compensating orthostatic perturbations. It has been established that the decrease in OS under the influence of microgravity is determined by a reduction of the vasoconstrictive ability of large blood vessels of the lower extremities; an increase in venous distensibility and capacitance of the legs; and an impairment of blood flow regulation, which leads to a cerebral blood flow deficit in orthostatic stresses, and of the initial individual OS before the flight. The results of preflight studies of hemodynamics by ultrasonic methods at LBNP and the data of orthostatic tests before SFs make it possible to predict the degree of decrease of OS after an SF proceeding in the normal mode. At the same time, the data of ultrasonic blood flow examination provide more a accurate estimation of OS and make it possible to assess the physiological reserves of hemodynamic regulation and to reveal the loss of regulation capacity even in cases where integrated indices (heart rate and blood pressure) are within the normal ranges.     

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.     

Metabolic features of cosmonauts after ballistic descent from the Earth orbit

The features of metabolic reactions in five cosmonauts after long-term flights on the International Space Station (ISS) and landing along a ballistic trajectory and in the cosmonauts returning to Earth in the mode of automatic controlled descent were studied. Venous blood samples were collected, and 50 biochemical parameter values that reflect the functional state of organs and tissues and characterize the main metabolic pathways were determined. On the first day of the recovery period after ballistic descent, the activity of the myocardial, liver, and gastrointestinal enzymes in the blood serum of cosmonauts was increased 1.3- to 2.1-fold; a number of the parameter values exceeded the upper normal limit. The level of C-reactive protein increased fivefold as compared with the preflight values. Marked signs of glycolysis, glycogenolysis and lipolysis activation as well as disorders of acid–base balance were observed. Changes in the biochemical parameter values in cosmonauts after landing along a ballistic trajectory differed significantly from those revealed in the same cosmonauts after long-term missions followed by automatic controlled descent to Earth. Negative metabolic changes tendency after landing along a ballistic trajectory remained for at least 14 days of the recovery period. It was concluded that changes in the metabolic reactions of cosmonauts after long-term missions to the ISS depend on the flights final stage conditions. After landing on Soyuz spaceships in the ballistic descent mode, the cosmonauts had adverse prognosis changes in the biochemical values characterizing the state of the cardiovascular system and marked shifts in the activity of the liver and gastrointestinal constellation enzymes. The dynamics of carbohydrate, lipid, and protein metabolism as well as acid–base balance indicates a significant tension of all body systems and exhaustion of its functional reserves.     

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.     

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.     

Changes in beta-adrenergic regulation of the cardiovascular system during aging

Changes in beta-adrenergic regulation of the cardiovascular system in aging involved 40 healthy subjects aged 20-34, 60-74 and 75-89 have been studied. Single drug loads with propranolol (0.6 mg/kg, per os) and isadrin (10 mg, sublingually) were used. With aging, the beta-adrenergic regulation of heart at various levels (in the central and autonomic vegetative nervous system, the ACTH-cortisol system) changes. The negative effect of beta-adrenergic blockade on the cardiovascular system enhances, that is a result of a more significant suppression of the sympathetic effects on the heart and peculiarities of the propranolol pharmacokinetics in old age. The reactivity of beta-adrenergic mechanisms in response to their stimulation decreases as well. Blockade of the beta-adrenoreceptors produces a distinct saving effect on the performance of the cardio-respiratory system under conditions of physical loading, that is due to a suppression of sympathetic hyperactivity and elimination of excess strain in the ACTH-cortisol system at the peak submaximal physical loading.     

Effect of environment on the functional state of adolescents

Adolescents of both sexes 14–15 years of age residing under different environmental conditions have been examined. The group exposed to atmospheric pollution with sulfur-containing substances from a pulp-and-paper mill, as compared with the control (residing in a relatively “clean” area), is characterized by lower tolerance to hypoxemia, reserves of the cardiorespiratory system, core body temperature, level of physical health, concentrations of nitrogen oxide metabolites in the blood, and antioxidant vitamin supply. In addition, this group shows a tendency towards hypertension and worsening of hemodynamic regulation.     

Prognostic Values of Some Cardiovascular Risk Factors in Cosmonauts

A ten-year follow-up study was focused on comparison of risk factors of atherosclerosis and damage to target organs in a group of 40- to 65-year-old cosmonauts and volunteers in the same age range. It was shown that the incidence of supraventricular extrasystoles in the groups increased with aging by 85 and 80%, respectively, inferring the risk of supraventricular tachyarrhythmias. The primary predictors of atherosclerosis and coronary artery disease (CAD) in cosmonauts are decreased endothelium-dependent vasodilation in the right brachial artery, C-reactive protein (hsCRP) level > 2 mg/L, and high atherogenic index. These CAD predictors should be of particular concern during medical screening of candidates for cosmonauts.     

Cell-mediated retraction versus hemodynamic loading – A delicate balance in tissue-engineered heart valves

Preclinical studies of tissue-engineered heart valves (TEHVs) showed retraction of the heart valve leaflets as major failure of function mechanism. This retraction is caused by both passive and active cell stress and passive matrix stress. Cell-mediated retraction induces leaflet shortening that may be counteracted by the hemodynamic loading of the leaflets during diastole. To get insight into this stress balance, the amount and duration of stress generation in engineered heart valve tissue and the stress imposed by physiological hemodynamic loading are quantified via an experimental and a computational approach, respectively.     

Characteristics of adaptation and maladaptation of human cardiovascular system under space flight conditions

The goal of this study was to analyze and generalize hemodynamic data collected over 20 years from 26 cosmonauts, who had flown from 8 to 438 days aboard orbital stations Salut-7 and Mir. This paper describes the results of ultrasonographic studies of the heart and arterial and venous peripheral vessels in different parts of human body as well as the study of venous capacity by occlusion aeroplethysmography. It was established that, at rest, the key hemodynamic parameters (the pumping function of the heart and blood supply of the brain) and integral parameters (blood pressure and heart rate) were best “protected” and remained stable throughout long exposure in microgravity. In the absence of gravitational stimulation, arterial resistance decreased in almost all vascular regions below the heart level; i.e., the antigravity distribution of the vascular tone was gradually lost as unneeded in microgravity. Venous hemodynamics was found to be most sensitive to microgravity: changes in it were expressed earlier and were more pronounced than in the arterial part of the vasculature. The changes included deceleration of venous return, a decrease in the vascular resistance in the lower body, and an increase in the leg’s venous network capacity. The functional test with the lower body’s negative pressure revealed a deterioration of gravity-dependent responses, which increased with an increase in the duration of the space flight. Cardiovascular deconditioning clearly manifested itself after the return to the Earth’s gravity as a decreased g-tolerance during reentry and orthostatic instability in the post-flight period. The results of this study confirmed the multifactorial genesis of orthostatic instability during space flights including blood redistribution, changes in the regulation of vascular tone of arterial and venous vessels in legs, and hypovolemia.     

The effect of a long stay under microgravity on the vestibular function and tracking eye movements

Pre-and postflight examinations of cosmonauts participating in missions ISS-3 to ISS-9 on the International Space Station were performed using a computer-aided method of integrated assessment of the oculomotor system. The role and significance of the vestibular system in the eye tracking were determined; the individual and general characteristics of spontaneous oculomotor reactions and oculomotor reactions induced by visual and vestibular stimuli after a long-term stay at zero gravity (126–195 days) were determined; and the changes in the indices of oculomotor reactions were monitored. Studies of the vestibular function, intersensory interactions, and the tracking function of the eyes in the crew members were performed on the second, fifth (sixth), and ninth (tenth) days of the readaptation period. The results of the postflight examinations showed a significant change in the accuracy, velocity, and temporal characteristics of eye tracking and an increase in the vestibular reactivity. It was shown that the structure of visual tracking (the accuracy of fixational eye rotations and smooth tracking) was disturbed (the appearance of correcting saccades, the transition of smooth tracking to saccadic tracking) only in those cosmonauts who, in parallel to an increased reactivity of the vestibular input, also had central changes in the oculomotor system (spontaneous nystagmus, gaze nystagmus). With one exception, recovery of the indices of the accuracy of tracking eye movements in cosmonauts to the background level in the selected period of examination was not observed, although a positive trend was recorded.     

The effect of body mass on physiological indicators in the performance of forestry workers

The paper presents the results of research into the effects of body mass (BM) on basic physiological indicators of work capability among forestry workers. The indicators included the maximum theoretical heart rate, the maximum heart rate in exertion tests, and the basal energy expenditure. The effects of the deviation of the actual from the ideal BM values were analysed on a sample of 8 workers. The variables included age, body height and mass. These were used to determine the maximum theoretical heart rate. The maximum heart rate was determined in an ergonomic laboratory in a programmed exertion test on a treadmill. Using standard formulae in work physiology, values of work capability indicators were calculated for the actual and ideal BM of each worker. The results, embracing individual and summary values and their absolute and relative ratios, showed that workers exceeded their ideal BM by an average of 9.9 kg. In all workers, the maximum theoretical heart rate was higher than that achieved in the exertion test. It was also found that even significant deviations of the ideal from the actual BM (the actual BM was more than 20% higher than the ideal BM) did not have any considerable effects on the maximum theoretical heart rate. The analysis of oxygen consumption showed that in relation to physical capability of the ideal BM and the maximal theoretical heart rate, physical capability of each worker was lower by an average of 11.5%. The highest reduction of physical capability was found in those workers with the least favourable ratio between the theoretical and the maximal tested heart rate. It was concluded that on average, the basal energy expenditure in each worker was higher by 7.45% due to the deviation of the actual from the ideal BM. At constant values of other factors, this means an equivalently lower capacity for daily physical performance.     

Reference values of the hemostasis system indices in cosmonauts

The values of 11 diagnostically significant hemostasis system indices were determined during the preflight (30–45 days before start) clinical and physiological examination of 39 cosmonauts aged 35 to 54 years, who were the members of the main and backup crews of missions to the International Space Station (ISS) during the period from 2007 to 2014. Since most of the cosmonauts performed several flights over this period and were repeatedly included in backup crews, each of them underwent examinations one to five times. The reference values were calculated for each of the studied indices. It was found that the reference ranges for the parameters indicative of the integral pro- and anticoagulant and fibrinolytic blood plasma potential were somewhat narrowed and close to the boundaries of general population ranges, which indicates that the cosmonauts had a relatively decreased procoagulant potential and increased regulative potential of the hemostasis system. This was probably due to the criteria of selection, physical training status, and emotional status of crew members during the preflight professional activity, when adaptive changes against stressinducing effects occur in the body. The cosmonauts who underwent strict medical examination may also have some genetic features in which they differ from the general population and which provide higher body resistance and more rapid adaptation processes.     

The Effect of Long-term Space Flights on Human Urine Proteins Functionally Related to Endothelium

It is known that long-term space flights lead to dysregulation of the cardiovascular system, and the endothelium is the most important functional element of such dysregulation. In order to find the signs of endothelial dysfunction in cosmonauts who have been in long-term space flights, we collected urine samples from 21 cosmonauts before the flight and on the first and seventh days after landing. The urine samples were investigated by chromatography–mass spectrometry analysis. Proteins were identified using the MaxQuant software and the SwissProt database. The software package Perseus was used for semi-quantitative analysis. The reconstruction of associative molecular networks was performed using the ANDSystem software. We identified 200 different proteins in urine samples of 21 Russian cosmonauts. The ANDSystem software made it possible to determine seven processes related to endothelium functioning. These processes had direct relations to 17 urine proteins, which were functionally associated with the endothelium. At the same time, eight proteins (such as serotransferrin, prostate-specific antigen, fibrinogen gamma chain, UFO tyrosine kinase receptor, aminopeptidase N, vascular cell adhesion molecule 1, osteopontin, and syndecan-4) were significantly changed (p < 0.01) at different points of the recovery period (the first and seventh days). Thus, we performed the first study of the urine protein composition in cosmonauts for the evaluation of signs of endothelial dysfunction after space flight using proteomics methods.     

Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method.

Reduction in plasma volume is a major contributor to orthostatic tachycardia and hypotension after spaceflight. We set out to determine time- and frequency-domain baroreflex (BRS) function during preflight baseline and venous occlusion and postflight orthostatic stress, testing the hypothesis that a reduction in central blood volume could mimic the postflight orthostatic response. In five cosmonauts, we measured finger arterial pressure noninvasively in supine and upright positions. Preflight measurements were repeated using venous occlusion thigh cuffs to impede venous return and "trap" an increased blood volume in the lower extremities; postflight sessions were between 1 and 3 days after return from 10- to 11-day spaceflight. BRS was determined by spectral analysis and by PRVXBRS, a time-domain BRS computation method. Although all completed the stand tests, two of five cosmonauts had drastically reduced pulse pressures and an increase in heart rate of approximately 30 beats/min or more during standing after spaceflight. Averaged for all five subjects in standing position, high-frequency interbeat interval spectral power or transfer gain did not decrease postflight. Low-frequency gain decreased from 8.1 (SD 4.0) preflight baseline to 6.8 (SD 3.4) postflight (P = 0.033); preflight with thigh cuffs inflated, low-frequency gain was 9.4 (SD 4.3) ms/mmHg. There was a shift in time-domain-determined pulse interval-to-pressure lag, Tau, toward higher values (P < 0.001). None of the postflight results were mimicked during preflight venous occlusion. In conclusion, two of five cosmonauts showed abnormal orthostatic response 1 and 2 days after spaceflight. Overall, there were indications of increased sympathetic response to standing, even though we can expect (partial) restoration of plasma volume to have taken place. Preflight venous occlusion did not mimic the postflight orthostatic response.