Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station.

Impaired autonomic control represents a cardiovascular risk factor during long-term spaceflight. Little has been reported on blood pressure (BP), heart rate (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We tested the hypothesis that cardiovascular control remains stable during prolonged spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency (RF) were assessed in eight male cosmonauts (age 41-50 yr, body-mass index of 22-28 kg/m2) during long-term missions (flight lengths of 162-196 days). Recordings were made 60 and 30 days before the flight, every 4 wk during flight, and on days 3 and 6 postflight during spontaneous and controlled respiration. Orthostatic testing was performed pre- and postflight. RF and BP decreased during spaceflight (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change during spaceflight. However, the individual responses were different and correlated with preflight values. Pulse-wave transit time decreased during spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min) decreased in six and increased in one cosmonaut during flight. The most pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP and RF combined with stable HR and HRV during flight suggest functional adaptation rather than pathological changes. Pulse-wave transit time shortening in our study is surprising and may reflect cardiac output redistribution in space. The decrease in HRV during controlled respiration (6 breaths/min) indicates reduced parasympathetic reserve, which may contribute to postflight disturbances.     

Study of the autonomic regulation of blood circulation during a long-term space flight

The five-year experience of experimentation in the autonomic regulation of blood circulation on board the International Space Station is presented. The heart rate variability (HRV) analysis was the basic methodical approach in these investigations. The probabilistic approach to the estimation of the risk of pathology under long-term spaceflight conditions based on HRV analysis is described. The individual type of autonomic regulation was taken into account in the analysis of the results of the investigations. The type of regulation inherent in every cosmonaut under the conditions of weightlessness has been shown to be retained during subsequent flights. New scientific data on the relationship between the character of the adaptive response of the body to spaceflight factors and the individual type of autonomic response have been obtained. Staying in weightlessness has been shown to be connected with the readjustment of regulatory systems and with transition to the zone of prenosological states. Adaptation responses in weightlessness are characterized by the increased tension of the regulatory systems and the preservation of sufficient functional reserves. The mobilization of additional resources is required after returning to earth, due to which the functional reserve of the mechanisms of regulation decreases. Cosmonauts with the vagotonic and normosympathotonic types of autonomic regulation appear to be the most resistant. The knowledge of the type of autonomic regulation allows us to judge the potential response of the cosmonaut to spaceflight factors. The likelihood estimates were calculated, and the risk categories were determined by the results of HRV analysis in the last months of the flight. Three pathology risk groups were identified. In conclusion, the theoretical and applied significance of the experiments was considered.     

Biofeedback of Heart Rate Variability and Related Physiology: A Critical Review

Low heart rate variability (HRV) characterizes several medical and psychological diseases. HRV biofeedback is a newly developed approach that may have some use for treating the array of disorders in which HRV is relatively low. This review critically appraises evidence for the effectiveness of HRV and related biofeedback across 14 studies in improving (1) HRV and baroreflex outcomes and (2) clinical outcomes. Results revealed that HRV biofeedback consistently effectuates acute improvements during biofeedback practice, whereas the presence of short-term and long-term carry-over effects is less clear. Some evidence suggests HRV biofeedback may result in long-term carry-over effects on baroreflex gain, which is an area most promising for future investigations. On the other hand, concerning clinical outcomes, there is ample evidence attesting to efficacy of HRV biofeedback. However, because clinical and physiological outcomes do not improve concurrently in all cases, the mechanism by which HRV biofeedback results in salutary effects in unclear. Considerations for the field in addressing shortcomings of the reviewed studies and advancing understanding of the way in which HRV biofeedback may improve physiological and clinical outcomes are offered in light of the reviewed evidence.     

Mechanisms of human osteopenia and some peculiarities of bone metabolism in weightlessness conditions

Systematically results and new analysis data on the investigation of human bone system in space flight, the orbital station Mir and International Space Station, are presented. The bone mineral density, bone mineral content, identified as bone mass and body composition using dual energy X-ray absorptiometry were measured. Theoretically, an expected bone mass loss in trabecular tissue of lower skeletal half may by described as a quickly developing but reversible osteopenia and considered as evidence of functional adaptation of bone tissue to the changing mechanical load. A hypothesis of main mechanisms of osteopenia in microgravity is presented. High individual variability of bone mass losses and stability of individual pattern of correlation between bone mass losses in different skeletal segments were found. It is not possible to identify the relationship between bone mass losses and duration of space missions. Therefore it is not a sufficient ground to calculate the probability of reaching the critical level of bone demineralization by prolonged space flight. The same relates to the probability of prognosis of bone quality changes. There is data about dual energy X-ray absorptiometry that is insufficient for this prognosis. The main direction of investigations is presented which might optimize the interplanetary mission from the point of view of skeletal mechanical functions preservation.     

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.     

Effects of long-term fixation on histological quality of undecalcified murine bones embedded in methylmethacrylate.

While long-term fixation and storage of specimens is common and useful for many research projects, it is particularly important for space flight investigations where samples may not be returned to Earth for several months (International Space Station) or years (manned mission to Mars). We examined two critical challenges of space flight experimentation: the effect of long-term fixation on the quality of mouse bone preservation and the preservation of antigens and enzymes for both histochemical and immunohistochemical analyses, and how the animal/sample processing affects the preservation. We show that long-term fixation minimally affects standard histological staining, but that enzyme histochemistry and immunolabeling are greatly compromised. Further, we demonstrate that whole animal preservation is not as suitable as whole leg or stripped leg preservation for long-term fixation and all histological analyses. Overall, we recommend whole leg processing for long-term storage of bone specimens in fixative prior to embedding in plastic for histological examination.     

Effects of long-term fixation on histological quality of undecalcified murine bones embedded in methylmethacrylate

While long-term fixation and storage of specimens is common and useful for many research projects, it is particularly important for space flight investigations where samples may not be returned to Earth for several months (International Space Station) or years (manned mission to Mars). We examined two critical challenges of space flight experimentation: the effect of long-term fixation on the quality of mouse bone preservation and the preservation of antigens and enzymes for both histochemical and immunohistochemical analyses, and how the animal/sample processing affects the preservation. We show that long-term fixation minimally affects standard histological staining, but that enzyme histochemistry and immunolabeling are greatly compromised. Further, we demonstrate that whole animal preservation is not as suitable as whole leg or stripped leg preservation for long-term fixation and all histological analyses. Overall, we recommend whole leg processing for long-term storage of bone specimens in fixative prior to embedding in plastic for histological examination.     

Head out of water immersion as simulation study: an heart rate variability study

During head out of water immersion (HOI), the hydrostatic pressure on the tissues of the lower limbs causes an increase in thoracic blood volume and a high vascular perfusion. This blood shift results in changes in autonomic balance. The aim of this study was to evaluate the activity of the autonomic nervous system, as obtained from the analysis of heart rate variability (HRV), during HOI at 2 different temperatures and compare these results with data obtained during parabolic flight. In HOI, two different positions (sitting and standing) were compared. Results showed a shift to vagal activity as well during HOI as in microgravity during parabolic flight.     

Spectral analysis of photoplethysmographic signals: The importance of preprocessing

Heart rate variability (HRV) is an important and useful index to assess the responses of the autonomic nervous system (ANS). HRV analysis is performed using electrocardiography (ECG) or photoplethysmography (PPG) signals which are typically subject to noise and trends. Therefore, the elimination of these undesired conditions is very important to achieve reliable ANS activation results. The purpose of this study was to analyze and compare the effects of preprocessing on the spectral analysis of HRV signals obtained from PPG waveform. Preprocessing consists of two stages: filtering and detrending. The performance of linear Butterworth filter is compared with nonlinear weighted Myriad filter. After filtering, two different approaches, one based on least squares fitting and another on smoothness priors, were used to remove trends from the HRV signal. The results of two filtering and detrending methods were compared for spectral analysis accomplished using periodogram, Welch's periodogram and Burg's method. The performance of these methods is presented graphically and the importance of preprocessing clarified by comparing the results. Although both filters have almost the same performance in the results, the smoothness prior detrending approach was found more successful in removing trends that usually appear in the low frequency bands of PPG signals. In conclusion, the results showed that trends in PPG signals are altered during spectral analysis and must be removed prior to HRV analysis.     

Short-Term Heart Rate Variability—Influence of Gender and Age in Healthy Subjects

In the recent years, short-term heart rate variability (HRV) describing complex variations of beat-to-beat interval series that are mainly controlled by the autonomic nervous system (ANS) has been increasingly analyzed to assess the ANS activity in different diseases and under various conditions. In contrast to long-term HRV analysis, short-term investigations (<30 min) provide a test result almost immediately. Thus, short-term HRV analysis is suitable for ambulatory care, patient monitoring and all those applications where the result is urgently needed. In a previous study, we could show significant variations of 5-min HRV indices according to age in almost all domains (linear and nonlinear) in 1906 healthy subjects from the KORA S4 cohort. Based on the same group of subjects, general gender-related influences on HRV indices are to be determined in this study. Short-term 5-min HRV indices from linear time and frequency domain and from nonlinear methods (compression entropy, detrended fluctuation analysis, traditional and segmented Poincaré plot analysis, irreversibility analysis, symbolic dynamics, correlation and mutual information analysis) were determined from 782 females and 1124 males. First, we examined the gender differences in two age clusters (25–49 years and 50–74 years). Secondly, we investigated the gender-specific development of HRV indices in five age decade categories, namely for ages 25–34, 35–44, 45–54, 55–64 and 65–74 years. In this study, significant modifications of the indices according to gender could be obtained, especially in the frequency domain and correlation analyses. Furthermore, there were significant modifications according to age in nearly all of the domains. The gender differences disappeared within the last two age decades and the age dependencies disappeared in the last decade. To summarize gender and age influences need to be considered when performing HRV studies even if these influences only partly differ.     

Development of a whole blood staining device for use during space shuttle flights.

BACKGROUND: Exposure to microgravity during space flight results in profound physiologic changes. Numerous studies have shown changes in circulating populations of peripheral blood immune cells immediately after space flight. It is currently unknown if these changes result from exposure to microgravity or are caused by the stress of reentry and readaptation to gravity. METHODS: We have developed the whole blood staining device (WBSD) as a system for the staining of whole blood collected during space flight for subsequent flow cytometric analysis. This device contains all liquids to address safety issues concerned with space flight and also moves the cells through the staining, lyse/fixation, and dilution steps. RESULTS: Data from flow cytometric analysis of samples stained in the WBSD was found to be comparable to data from samples stained by the conventional methods. Cells stained with the WBSD remain stable in the device for up to 14 days. The necessary manipulations required to use the device were tested on the KC-135 aircraft during the reduced gravity segment of parabolic flight. CONCLUSIONS: With the WBSD immunophenotype analysis can be performed at various time points for the duration of an entire Shuttle flight. In addition, this device has significant terrestrial applications for rapid and easy immunofluorescence labeling of whole blood in remote and isolated locations where immediate access to specialized equipment and skilled laboratory personnel may not be available. The WBSD provides a simple mechanism to design specific immunophenotyping tests for use by nontechnical personnel at bedside or in field locations. Cytometry 37:74-80, 1999. Published 1999 Wiley-Liss, Inc.     

Effects of long-term space flights on the organization of the horizontal gaze fixation reaction

The results of the Russian-Austrian space experiment Monimir, which was a part of the international space program Austromir, are presented. The characteristics of the horizontal gaze fixation reaction (hGFR) to the visual targets were studied during long-term space flights. Seven crewmembers of the space station Mir participated in our experiment. The subjects were tested four times before the flight, five times during the flight, and three to four times after landing. During the flight and after accomplishing, the characteristics of gaze fixation reaction changed regularly: the reaction time and coefficient of the gain of vestibular-ocular reflex increased; the velocities of eye-head movements increased and decreased. These changes were indicative of a disturbed control of the vestibular-ocular reflex under microgravity conditions because of variability of the vestibular input activity. The cosmonauts that had flight and non-flight professional specializations differed in strategies of their adaptation to the microgravity conditions. In the former, exposure to microgravity was accompanied by gaze hypermetry and inhibition of head movements; conversely, in the latter, the velocity of head movements increased, whereas that of saccades decreased.     

Temporal contribution of body movement to very long-term heart rate variability in humans

A newly developed, very long-term ( approximately 7 days) ambulatory monitoring system for assessing beat-to-beat heart rate variability (HRV) and body movements (BM) was used to study the mechanism(s) responsible for the long-period oscillation in human HRV. Data continuously collected from five healthy subjects were analyzed by 1) standard auto- and cross-spectral techniques, 2) a cross-Wigner distribution (WD; a time-frequency analysis) between BM and HRV for 10-s averaged data, and 3) coarse-graining spectral analysis for 600 successive cardiac cycles. The results showed 1) a clear circadian rhythm in HRV and BM, 2) a 1/f (beta)-type spectrum in HRV and BM at ultradian frequencies, and 3) coherent relationships between BM and HRV only at specific ultradian as well as circadian frequencies, indicated by significant (P < 0.05) levels of the squared coherence and temporal localizations of the covariance between BM and HRV in the cross-WD. In a single subject, an instance in which the behavioral (mean BM) and autonomic [HRV power >0.15 Hz and mean heart rate (HR)] rhythmicities were dissociated occurred when the individual had an irregular daily life. It was concluded that the long-term HRV in normal humans contained persistent oscillations synchronized with those of BM at ultradian frequencies but could not be explained exclusively by activity levels of the subjects.     

低压舱模拟飞行对于脑力负荷影响的初步探讨

目的：通过低压舱模拟飞行环境下被试人员生理指标的变化,探讨飞行员脑力负荷的变化规律。方法：21名男性志愿者参加低压舱模拟飞行的实验过程,座舱内的压力高度模拟2400米高空压力,持续时间1．5h,重复两次,中间出舱休息0．5h,检测指标为心率变异性（HRV）,心理运动测验以及NASA—TLX主观评定量表。结果：研究表明,NASA－TLX量表从主观感受上很好的反映了低压舱模拟飞行后脑力负荷的变化,HRV、心理运动测验也发生了相应的变化。结论：本研究结果提示低压舱模拟飞行所导致的脑力负荷变化是具有一定规律的,生理心理测验可能是测定变化规律的一种间接方法。     

Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV) signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.     

Emphasis of biological research for space radiation]

The paper summarized issues, current status and the recent topics in biological research of space radiation. Researches to estimate a risk associated with space radiation exposure during a long-term manned space flight, such as in the International Space Station, is emphasized because of the large uncertainty of biological effects and a complexity of the radiation environment in space. The Issues addressed are; 1) biological effects and end points in low dose radiation, 2) biological effects under low dose rate and long-term radiation exposure, 3) modification of biological responses to radiation under space environments, 4) various aspects of biological end points vs. cellular and molecular mechanisms, 5) estimation of human risk associated with radiation exposure in space flight, 6) regulations for radiation exposure limits for space workers. The paper also summarized and introduced recent progress in space related radiation researches with various biological systems.     

Strategies of cell biology experimentation in space

The purpose of this article is to inform newcomers on the most important aspects of experimentation with living cells and tissues in space laboratories and platforms. There are strong arguments that justify the efforts and investments in such activity. Experimentation in space is subject to safety and technological constraints that require considerable attention to the development of the flight protocols and of the flight instrumentation. Nevertheless to fly an experiment in space is a unique opportunity to study living systems under conditions not reproducible on Earth and it is also a contribution to human exploration of space. Thereby important progress in basic and applied science can be expected. Parallel investigations on ground with devices averaging the exposure to the gravity vector but not reproducing microgravity shall always be part of a space flight project.     

Autonomic cardiac control in animal models of cardiovascular diseases. I. Methods of variability analysis.

Analysis of heart rate variability (HRV) and blood pressure variability (BPV) and baroreceptor sensitivity (BRS) has become a proven tool in clinical cardiovascular diagnostics and risk stratification. In the present work, traditional and new methodological approaches for analysis of HRV, BPV, and BRS data are summarized. HRV, BPV, and BRS parameters were obtained from animal studies designed to study pathogenetic mechanisms of distinct cardiovascular diseases. Different non-linear approaches for HRV and BPV analysis are presented here, in particular measures of complexity based on symbolic dynamics. The dual sequence method (DSM) was employed for BRS analysis. In comparison to the classical measure of BRS using the average slope [ms/mm Hg], DSM offers additional information about the time-variant coupling between BPV and HRV. Since cardiovascular regulation shares common features among different species, data on HRV and BPV, as well as BRS, in animal models might be useful for understanding the pathogenetic mechanisms of cardiovascular diseases in humans and in the development of new diagnostic approaches.     

Frequency characteristics of long-term heart rate variability during constant-routine protocol

The effects of such behavioral factors as physical activity, food intake, and circadian rhythm on long-term heart rate variability (HRV) in humans remain poorly understood. We therefore studied their effects on HRV using a constant-routine protocol that included simultaneous core body temperature (CBT) correction. Seven healthy subjects completed the constant-routine and daily-routine protocols, during which HRV and CBT were continuously monitored. During the constant routine, subjects were kept awake for 27 h in a semirecumbent posture with minimal physical activity; small isocaloric meals were provided every 2 h. During the daily routine, subjects carried on their lives normally. Data were analyzed using generic spectral analysis based on a fast Fourier transform; coarse-graining spectral analysis was also used to eliminate periodicity due to the regular meals for raw HRV and for the CBT-corrected HRV without circadian and/or low-frequency ultradian components. The results showed that 1) the power spectra of HRV in the constant routine and daily routine had similar power-law scalings at frequencies above approximately 10(-3.5) Hz, while 2) below that crossover frequency, HRV was smaller in the constant routine than in the daily routine, with the difference becoming significant (P < 0.05) at <10(-4) Hz, 3) coarse-graining spectral analysis eliminated diet-induced peaks in generic spectral analysis-based HRV spectra during the constant routine and emphasized the crossover at approximately 10(-3.5) Hz, and 4) CBT correction did not alter the results. Below a frequency of approximately 10(-3.5) Hz (a period >1 h), HRV is strongly influenced by behavioral factors; above that crossover frequency, HRV is behavior independent, possibly reflecting an intrinsic regulatory system.     

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.