The paper presents the main results of experiments devoted to studying the influence of simulated microgravity and lunar gravity on the function of external respiration in humans. It has been shown that influence of human exposure to head-down bed rest (a model of the physiological effects of microgravity) and head-up bed rest (a model of the physiological effects of lunar gravity), similar to the influence of a horizontal position (bed rest), leads to a clinically insignificant decrease in the main respiratory parameters in the first hours of these analog ground-based investigations. Subsequently, during hypokinesia, the marked changes gradually level out. After cessation of experimental exposures, parameters of external respiration function are at the level of background values.

The paper reports the major results of an IBMP bedrest study with the emphasis on its preparation and implementation. The study involved 12 healthy males (29.8 ± 4.6 years of age, M ± SD) volunteered for a 21-d head-down bed rest at –6° (HDBR). Body length, mass and water balance were measured daily (2 days prior, during and in 2 days after HDBR). Routine checkups were performed twice a day. They included heart rate (HR), blood pressure(BP) and temperature measurements, and recording complaints, if any. Data analysis pointed to a tendency for body elongation and mass loss in the period of acute adaptation; these changes retained till the end of HDBR. Water balance was noted to be negative during HDBR but became positive on completion. HR, BP and body temperature were decreased in the early HDBR period and increased significantly on the first day after its completion. The most common complaints were about back discomfort, generally inthe lumbar region.

Ratio of blood pressure (BP) and heart rate (HR) has been used as a quantitative indicator of the human orthostatic tolerance. The indicator was conventionally designated as an efficiency coefficient (EC) of the mechanisms involved in systemic BP control during the passive orthostatic test (POT). The coefficient is measured in conventional units and calculated by formula EC (conv.unit) = BP (mm Hg) / HR (beats/min). Informativity of this indicator was verified by means of a retrospective analysis of 118 POTs performed by 30 essentially healthy male subjects (aged 19 to 40 yrs) before and after bed rest of varying duration. Prior to POT, EC in supine position made up 1.88 ± 0.04 conv. units. The EC decrease to 1.3 – 0.95 conv. units during POT evidenced clearly the extent of changes in the cardiovascular functioning and POT endurance. After bed rest, all subjects demonstrated an increased cardiovascular strain and reduced POT endurance; however, EC values were reliably higher for the subjects who had shown a higher POT endurance before bed rest. Based on analysis of individual reactions, the EC reduction to 1 conv.unit corresponded to the first pre-collapse signs and called for immediate POT termination. These results of the investigation make us believe that EC is an informative objective criterion for orthostatic tolerance evaluation that can be proposed for aerospace medicine applications.

Interrelation between blood redistribution toward the upper part of the body in microgravity and changes in sensitivity of the central respiratory mechanism was studied with participation of 16 Russian members of the International space station crews (40-57 year-old males). Time of maximal voluntary breath-holding during inspiration (MVHins) and expiration (MVHexp) was measured prior to and following the 15-min low-body negative pressure test (LBNP, -25 mm Hg). Before launch, the baseline MVHins and MVHexp durations in the vertical position made up 61.9 ± 3.9 s and 24.5 ± 1.5 s, respectively. In the supine position, the parameters increased to 81.1 ± 5.6 s and 31.2 ± 1.9 s (p < 0.01), respectively. More significant increases of breath-holding were observed in space microgravity. On flight months 1-5, MVHins and MVHexp rose by 25–45.5 % and by 17.5–54.2 %, respectively. After return from space the initial values of the parameters were recovered. Comparison of the measurements made prior to and within 5-10 minutes after LBNP revealed a further gain in both MVHins and MVHexp. Breath-holding extension in the supine position (at 1 G) and in microgravity suggests attenuation of the respiratory center sensitivity to the physiological chemoreceptor stimuli, namely, increased РаСО2 and lowered РаО2. This attenuation is driven by the blood shift toward the upper part of the body that causes increase of the vascular pressure in the sinus carotid region and activation of baroreceptors. The conclusion results from the significantly greater time of breath-holding during LBNP in microgravity and supine position, as well as time reduction to the initial values on return from space mission.

The paper presents the main results of our study on the influence of the physiological effects of simulated lunar gravity on cardiorespiratory responses to exercise in humans. Twelve healthy male volunteers aged 19–31 years (M ± SD: 22.5 ± 4.0 years) took part in the study. They were under 14-day head-up bed rest (HUBR) at +9.6° angle relative to the horizon as a model of the physiological effects of lunar gravity. Cardiopulmonary exercise testing (CPET) was performed 7 days before the onset of HUBR and on the next day after the end of the experimental exposure. A three-stage cycle ergometer test with 5-min steps at 125, 150, and 175 W was used as a CPET protocol. Exposure of the subjects to simulated lunar gravity reduced their tolerance to physical load. This was indicated by more pronounced changes for such parameters of the cardiorespiratory system as heart rate, minute ventilation of the lungs, ventilatory equivalents for oxygen and carbon dioxide, as well as a less pronounced increase in oxygen consumption and oxygen pulse during CPET after 14 days of exposure to HUBR.

Effect of 14-day head up bedrest (HUBR) on the human orthostatic tolerance studied with participation of 23 essentially healthy male subjects at the age of 18 to 35 years. HUBR with the head-end tilted up at +9.6º was to imitate physiological effects of the lunar gravity. Orthostatic tolerance was tested on the day prior to and immediately after HUBR completion with subjects tilted up to +70° for 20 min maximum. The parameters registered before, during and after the tilt test included blood pressure, ECG and heart rate. In comparison with the baseline testing, HUBR reduced the number of completed tests and increased the number (10 vs. 4) of tests terminated for the reason of precollapse (p < 0.05). The group mean time of OS test tolerance decreased by 3.8 minutes (p < 0.01) and time interval between the test onset and precollapse decreased by 4.7 minutes (p = 0.055). For the most part, orthostatic disorders following HUBR were described as a vasodepressor type hypotension collapse with high activity of the chronotropic function of the heart. Several cases of vagus-mediated HR slowing pointed to a sharp decline of the sympathetic nervous activity which is an important mechanism of hemodynamics regulation in changed postural conditions.

This study involving ten apparently healthy male volunteers aged 19 to 31 years was aimed at establishing possible effects of a three-week course of normobaric intermittent hypoxic trainings (IHTs) on the state of endothelial function (EF). IHTs were performed on a daily basis with each training session lasting 60 min and the FIO2 operating level equal to 9% in the 5-min hypoxia/5-min normoxia cyclic mode. The EF state and the pulse wave velocity (PWV, ΔPWV) were evaluated using a Tonocard device by a noninvasive method based on the capacity of the endothelium to release nitric oxide (NO) during reactive hyperemia. The adaptation to intermittent hypoxia was accompanied by a significant (p < 0.05) 34.3% increase in the erythropoietin (Epo) concentration, a larger than twofold increase in the reticulocyte count, a 6.4% increase in the erythrocyte count, and a 4.1% increase in the hemoglobin content. After the course of IHTs, the value of EF used to increase significantly by 38.9% (p < 0.05), which could be caused by a higher level of endothelium-dependent relaxation in muscular arteries. At the same time, the PWV and ΔPWV values reflecting the elastic–viscous characteristics of vascular wall remained at the prior-to-the study level. The data obtained in the study are discussed in this article from the position of possible trigger effects of the hypoxia-inducible transcription factors (HIF-1 and HIF-2), which create a broad molecular basis for the activation of endothelial cells and the increase in the NO production. Apart from increasing the erythrocyte production, which is greatly important for maintaining oxygen homeostasis under reduced PO2, Epo can participate in the complicated mechanisms of ventilatory response, activation of NO production by endothelial cells, and angiogenesis during the adaptation of the body to hypoxia.

Предложен метод изучения нестационарной ритмограммы сердца, основанный на вейвлет-анализе частотно-модулированного сигнала. Пики кардиограммы в точности совпадают с моментами истинных сокращений сердца. В качестве примера рассмотрена проба с управляемым дыханием, которая состояла из трех этапов: этапа покоя (A), этапа ритмизированного дыхания с заданной частотой (B) и этапа релаксации (С). Продолжительности этапов A, B и С равнялись 15, 5 и 20 минут. Этап ритмизированного дыхания B представлял собой последовательность вдохов и выдохов, каждый из которых имел длительность 5 секунд. Дыхательные пробы были выполнены для 27 практически здоровых испытуемых в возрасте 18–22 лет. Количественные параметры, разрабатываемые в статье, представляют собой отношения спектральных интегралов частотно модулированного сигнала ритмограммы сердца. Спектральные интегралы вычислены для диапазонов сверхнизких, низких и высоких частот на этапах A, B, C. Произведена классификация испытуемых по степени воздействия дыхательной пробы на организм. Предлагаемый метод может найти применение при анализе переходных этапов ритмограммы для всех функциональных проб.

The authors proposes a method to study the non-stationary heart rhythmogram based on the wavelet analysis of a frequency-modulated signal. The peaks of the cardiogram coincide with heart contractions. The study included a test with controlled breathing, which consisted of three stages: a resting stage (A), a rhythmic breathing stage with a given frequency (B), and a relaxation stage (C). The duration of stages A, B and C were 15, 5 and 20 minutes, respectively. The rhythmic breathing stage B consisted of an inhalation/exhalation sequence, each lasting 5 seconds. Breathing tests were performed on 27 apparently healthy subjects aged 18–22. The quantitative parameters discussed in the article are the ratios of the spectral integrals of the frequency modulated signal of the heart rhythm. Spectral integrals were calculated for the ultra-low, low and high frequency ranges at stages A, B, and C. The subjects were classified according to their response to the breathing test. The proposed method can be used in the analysis of transient responses of the rhythmogram in all functional tests.

Введение. Снижение работоспособности и ортоустойчивости, наблюдаемых у космонавтов на разных этапах космического полета, диктует необходимость поиска новых методов, способствующих улучшению переносимости экстремальных факторов и восстановлению нарушенных функций организма, в реабилитационном периоде. Одним из перспективных направлений, повышающих общую неспецифическую резистентность организма являются гипоксические тренировки. Вместе с тем сведения о применении гипоксического воздействия непосредственно в условиях космического полета для нивелирования неблагоприятных эффектов невесомости отсутствует. Цель исследования - изучение влияния нормобарической периодической гипоксии на кардиореспираторные показатели и резервные возможности организма крыс при свободном двигательном режиме и в условиях антиортостатической гипокинезии (антиортостатическое вывешивание с углом наклона -30°), моделирующей физиологические эффекты невесомости. Методика. Проведено 4 серии экспериментов на 48 крысах Вистар, массой 280-300 г. Животные в течение 7 сут находились: в 1-й серии в свободном двигательном режиме с ежедневной 5-часовой нормобарической гипоксией (12% О2); во 2-й - в условиях антиортостатической гипокинезии после предварительного курса гипоксии; в 3-й - в антиортостатической гипокинезии без предварительной гипоксии (нормоксия 20,9% О2); в 4-й - в антиортостатической гипокинезии с ежедневной 5-часовой гипоксией. После завершения эксперимента у всех животных регистрировали кардиореспираторные показатели методом пневмотахографии, электрокардиографии, пульсоксиметрии, для оценки физической выносливости крыс использовали тест вынужденного плавания (по Порсолту). Результаты. Установлено, что эффективность НПГ в целях повышения функциональных резервов кардиореспираторной системы после длительного пребывания в условиях антиортостатической гипокинезии достигается только в результате предварительной адаптации (прекондиционирования) к периодической гипоксии в свободном двигательном режиме. Заключение. Воздействие нормобарической периодической гипоксии в условиях моделирования невесомости приводит к ухудшению функционального состояния организма и снижению физической выносливости крыс.Introduction. Restoring the physical condition of cosmonauts following a prolonged spaceflight requires new methods for improvement of resistance to extreme factors and recovery during the rehabilitation period. A promising approach to enhancing the general, nonspecific resistance to adverse environmental factors is hypoxic training. However, information about the use of hypoxia effects on the scene of a space flight to neutralize adverse effects of weightlessness is absent. Aim. To study the effect of intermittent normobaric hypoxia (INH) on cardiorespiratory parameters and reserve capacity of rats in free locomotion and in head-down tilt of -30°(HDT-30° ), a model of spaceflight. Methods. Experiments were performed on 48 Wistar rats weighing 280-300 g. For 7 days the animals were 1) in free locomotion with INH daily for 5-hours (12% O2); 2) in HDT-30o under normoxia following prior INH; 3) in HDT-30° under normoxia; 4) in HDT-30° in combination with INH. Cardiorespiratory parameters were recorded by pneumotachography, electrocardiography and pulse oximetry. Exercise tolerance was evaluated using the forced swimming test (Porsolt). Results. The effect of INH in increasing the cardiorespiratory functional reserve after long-term simulated microgravity is achieved only with prior adaptation (preconditioning) to INH in free locomotion. Conclusions. Intermittent normobaric hypoxia used in simulated microgravity leads to impairment of the functional state and decreases physical endurance of rats.

Adaptation to hypoxia is an important object of medical research. The aim of this study was to investigate the dynamics of blood oxygen saturation (SpO2), arterial blood pressure (BP), red blood cells, reticulocytes, hemoglobin and erythropoietin (EPO) concentrations during intermittent hypoxic training (IHT). The study was conducted in 11 healthy male volunteers; 2 regimens were tested: 11 and 14 days of IHT at FIO2 = 9%. Exposure to the hypoxic gas mixture caused a reduction in SpO2 by an average of 20.4% (p < 0.05), a 22% increase in the heart rate (p < 0.05) and a 4.5% decrease in diastolic BP (p < 0.05) relative to the initial levels. After 11 days of IHT training, the reticulocyte count was increased by 16.6% (p < 0.05), and there was a distinct tendency to elevated red blood cells (p > 0.05) and hemoglobin (p > 0.05). EPO concentrations declined by 44.2% (p < 0.05) relative to the initial level. Extending the regimen to 14 days resulted in a 3.9% increase in red blood cell count (p < 0.05) and a 4.7% elevation of hemoglobin concentrations (p < 0.05), accompanied by the recovery of the initial reticulocyte count. The applied 2-week IHT regimen resulted in the increased red blood cell count and elevated hemoglobin, suggesting an improvement in the oxygen-carrying capacity of the blood. The proposed regimen can be used to improve physical performance of individuals working in extreme environmental conditions.

Reduced orthostatic tolerance (OT) is a serious concern facing space medicine. This work sought to evaluate the effects of intermittent hypoxic training (IHT) on OT in humans before and after 3 days of head-down bed rest (HDBR) used to model microgravity. The study was carried out in 16 male volunteers aged 18 to 40 years and included 2 series of experiments with 11-day and 21-day IHT administered on a daily basis. During the first IHT session, the concentration of oxygen in the inspired gas mixture was 10%; for other sessions it was adjusted to 9%. OT was assessed by a 20-minute-long orthostatic tilt test (OTT) conducted before and after HDBR. Before HDBR, orthostatic intolerance was observed in 3 participants, while after HDBR, it was observed in 9 of 16 volunteers (p < 0.05). During OTT conducted after HDBR, the heart rate (HR) exceeded control values by 26.8% (p < 0.01). Preexposure to any of the applied IHT regimens led to a reduction in the number of volunteers with orthostatic intolerance. After the 11-day IHT program, there was a less pronounced increase in HR during OTT before HDBR; with the extended IHT regimen, less pronounced changes were observed for HR, systolic, diastolic and mean blood pressure (BP). The increase in HR during OTT after HDBR was significantly lower in the group that had completed the 11-day IHT program, while BP remained stable. The changes in HR and systolic BP were less pronounced in the group that had completed the 21-day IHT program than in the control group (p < 0.05). Thus, IHT reduced the risk of orthostatic disorders and mitigated changes in cardiovascular parameters during the orthostatic test.

The short- and long-term postural effects on the forced expiratory tracheal noise time were studied in a sample of 12 subjects. In contrast to the spirometric parameters, the tracheal forced expiratory noise time does not respond to a short-term change in the body posture from sitting and standing positions to the lying position, as well as to 14-day-long orthostatic hypokinesia in a lying position with a body angle of +9.6°. However, significant multidirectional individual dynamics of the tracheal forced expiratory noise time was observed in all subjects during long-term orthostatic hypokinesia, whereas the spirometric parameters had a dominant growth response. It is assumed that the estimation of the forced expiratory tracheal noise time during long-term orthostatic hypokinesia in lunar gravity simulation may provide useful data in addition to spirometry when assessing the individual lung function dynamics. The dynamics of acoustic parameters, as well as spirometric parameters, during long-term postural effects can be considered as adaptive changes.

Estimating the effect of microgravity/hypogravity on pulmonary ventilation function remains topical. Recently developed acoustic techniques based on the evaluation of the forced expiratory noise time (FETa) were hypothesized to be a promising tool for this aim. The aim of the protocol is to study the effect of two different modalities of bed rest space simulations (microgravity and lunar gravity) on FETa and spirometric indices. The FETa in the frequency band of 200-2000 Hz, recorded above human trachea, was evaluated. The 21st-day exposure to 6 degree head-down tilt (HDT) bed rest, simulating microgravity, and 9.6 degree head-up tilt (HUT) bed rest with head-zero tilt (HZT) rest intervals (HUT + HZT), simulating lunar gravity, in statistically identical subgroups of five and six healthy male volunteers, was studied. In the course of HDT bed rest, a significant elongation of FETa was found in relation to background measurements in "sitting" position (p = 0.016). The effect corresponded to a significant decrease of basic spirometric indices (p < 0.02). Moreover, FETa provided reliable discrimination of HDT and HUT + HZT bed rest tests (p = 0.018), while spirometric indices did not (p > 0.05). Based on previously found correlations (Korenbaum and Pochekutova, 2008; Malaeva et al., 2017), a FETa elongation in response to HDT bed rest was attributed to an increase of aerodynamic resistance of the respiratory tract. The technique seems promising to monitor human pulmonary ventilation dynamics in long-term space missions; however, new studies are welcome to verify it in real spaceflight.

The effects of adaptation to periodic normobaric hypoxia (PNH) on the intensity of orthostatic reactions were studied after long-term simulated microgravity in Wistar rats. It was established that exposure of animals to PNH prior to the simulated microgravity attenuates the orthostatic hypotension and increases orthostatic tolerance after simulated microgravity. It was assumed that the decrease in the intensity of hemodynamic orthostatic responses is a result of the positive cross-adaptation that occurs due to stabilization of the central intersystem reflex mechanisms, mediated both chemo- and baroreceptor regulation implemented on the new functional level.

A novel method of ground simulation in humans of physiological effects induced by the stay on the surface of celestial bodies with hypogravity was developed and successfully tested. This method is based on the change of gravity force angle, which decreases the gravitational component of the blood hydrostatic pressure characteristic of human vertical posture on the Earth and the load-weight onto the locomotor apparatus to the lower values expected at celestial bodies with hypogravity. The methodological requirements for ground simulation of the physiological effects of lunar gravity on human body are specified and substantiated by theoretical calculations. The experimental study revealed redistribution of liquid media in the human organism, functional changes in the cardiorespiratory system, and a decrease in the load-weight applied to the locomotor apparatus.