Microhemodynamic Adjustments and the Type of Autinomic Regulation Under Analog Long-term Isolation Conditions

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Heart rate variability analysis and laser Doppler flowmetry were used to assess cardiovascular system responses before, during, and after isolation. Volunteers demonstrated distinct autonomic regulation patterns, dividing into two groups based on vagal tone and vascular center activity. Group 2 showed consistently higher autonomic function throughout the experiment. Microcirculation parameters revealed decreased perfusion in the forehead area for Group 1 and fluctuating dynamics for Group 2. Both groups exhibited endothelial tone reduction and altered blood flow distribution in the toe area with increased shunt flow. Prolonged isolation significantly affects microhemodynamics and autonomic regulation. Individuals with higher vagal tone demonstrated better adaptation. These findings contribute to understanding physiological responses to long-term confinement and have implications for space mission medical support. Isolation conditions Cardiovascular system Autonomic regulation HRV analysis Microhemodynamics Laser Doppler flowmetry Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Leaving the Earth's surface, members of space crews experience not only the effects of physical factors: microgravity, radiation, noise from the equipment on the orbital station, and others (Shelhamer et al. 2020), but also face isolation, compounded by a limitation in the range of external conditions (Mircea et al. 2024). This isolation is unlike any that can be experienced on Earth. In earthly conditions, almost every one of us can break solitude by expanding our interaction with the surrounding world. Beyond the planet's orbit, even excursions into open space do not expand the confines of isolation. Yuri Alekseyevich Gagarin, the first human to make an orbital flight, was in such isolation for 108 minutes. Nowadays space crew members stay in it for about 180 days. For future space travelers, this time will significantly increase and be limited by the duration of the journey into deep space. Moreover, in the natural conditions of everyday life, each of us experiences the influence of a sufficiently broad spectrum of exogenous ecological conditions that determine adjustments (not so much homeostatic as allostatic) in the functioning of a living organism by seeking a constant equilibrium between its internal environment and the external surroundings (Sterling 2012; Goldstein 2019). In a confined orbital object, however, the range of changes in living conditions is limited to quite narrow boundaries. Social isolation, combined with the extremely limited area of orbital stations and living conditions, provokes a stressful state, while some familiar options for coping with it, such as the ability to take spontaneous walks, are absent among space crews. At the same time, their workload is extremely intense (Jacubowski et al. 2015), and their lifestyle and diet are very monotonous (Axpe et al. 2020). Prolonged stay of a person in a hermetic environment is accompanied by the effects of factors of a closed living volume, including: an artificial gas environment with relatively elevated levels of carbon dioxide compared to terrestrial conditions, the presence of artificial lighting, a regulated diet, a regime of physical activity, the occurrence of emergency situations, sleep deprivation, etc. Therefore, the study and analysis of the influence of multi-component conditions in an isolated volume on various systems of the human body holds significant scientific and practical importance (Orlov et al. 2023). Staying in a sealed atmosphere under controlled microclimate conditions, dietary conditions, and regulated physical activity has a pronounced effect on all physiological systems. Combined with other factors, such as elevated CO2 levels recorded aboard the International Space Station (ISS) (Fu et. al. 2019; Zhang et al. 2021) it can cause specific changes in the bodies of those performing their duties on board orbital stations, intensifying the effects of microgravity and the functional changes it causes (Goswami et al. 2021; Mircea et al. 2024). In recent years, a project called SIRIUS (Scientific International Research in Unique Terrestrial Station) (http://sirius.imbp.ru/ https://www.nasa.gov/humans-in-space/a-sirius-international-isolation-study/) has been implemented in Russia, consisting of a series of isolation experiments (4, 8, and 12 months) – an analog project for a lunar mission. In the United States, the CHAPEA (Crew Health and Performance Exploration Analog) project serves as an analog for a Mars mission (https://www.nasa.gov/humans-in-space/chapea/). The global research objectives of these isolation projects are related to studying the constraints experienced during long space flights, including limitations on communication and resources available to the crew, as well as equipment failures and other emergencies, the likelihood of which increases with greater distance from low Earth orbit (LEO) (Belakovskiy et al. 2011; Orlov et al. 2015; Gushchin et al. 2019). The effectiveness of various resource management strategies such as food systems, waste disposal, and water purification in isolated environments is experimentally evaluated (Baranov et al. 2021; Xu et al. 2024). In addition, the possibilities of potential conflicts and strategies for effective cooperation are assessed. Researchers are studying the psychological impact of isolation on small groups and the individual included in them, assessing the emotional state, cognitive functions and mechanisms of overcoming psychosocial deprivation (Plomariti et al. 2022; Ushakov et al. 2012). Undoubtedly, an important aspect of isolation projects is research on how isolation affects physical health, including basic physiological processes and their control mechanisms, as well as the development of crew selection and counter-measures, including medical ones, to help reduce the negative effects of isolation during future real-world space missions (Fedyay et al. 2023). Hermetic facilities are used for insulation projects, which make it possible to isolate volunteers for various periods of time in controlled environmental conditions: NEK (Ground-based Experimental Complex, IMBP, Russia) and HERA (Human Exploration Research Analog, NASA, USA), Yuegong-1 (Moon Palace, 月宫一号China). The NEK, where the SIRIUS project was conducted, is located on the territory of the IMBP RAS. It is a complex engineering facility (Fig. 1), consisting of interconnected multifunctional experimental modules: - small landing module (volume 50 m 3 ) - medical module (volume 100 m 3 ) - habitable module: command cabin, private cabins, dining room, wardroom (volume 150 m 3 ) - warehouse module: storage, greenhouse, gym (volume 250 m 3 ) - virtual simulator of the planet’s surface. The NEK life support system is equipped with autonomous ventilation and air conditioning systems, water supply, sewerage, electricity, and many others. Complex engineering communications form and maintain a habitat with preset parameters, isolating the crew from the environment and simulating the main factors of real space flight, with the exception of weightlessness and radiation exposure (Agaptseva et al. 2024). Our research scope in the SIRIUS project was related to the study of autonomic regulation and the functional state of the microcirculatory bed of the skin in healthy subjects during stay in a hermetic facility according to the scenario of an orbital flight to the Moon. In any extreme conditions, the body needs stability of the functions of the cardiovascular system (CVS) as one of the most important physiological systems that implements the possibility of adaptive changes (Goswami et al.2021). And, as has been shown, including in space flights, this is ensured by regulatory mechanisms (Baevsky et al. 2011; Otsuka et al. 2022). Adaptive changes in the blood flow regulation system affect all structural and functional components of the CVS. The microcirculatory bloodstream (MCB), at the level of which the gas transportation and exchange function is realized, is the final link of these processes. The human body's CVS performs a number of life-supporting functions, including transporting nutrients and oxygen to cells. In this regard, the MCB of the cardiovascular system, including arterioles, capillaries, arteriovenular anastomoses and venules, is of particular diagnostic interest. MCB directly provides transcapillary diffusion of oxygen and carbon dioxide, the general trophism of peripheral tissue structures of the body, as well as their adaptive stability under changing endogenous or exogenous conditions (Cracowski and Roustit 2020). A diagnostically significant feature of the MCB is its dynamic nature, as well as temporal and spatial functional heterogeneity. This makes the MCB the first link reflecting disturbances in the system of protective and adaptive reactions aimed at restoring impaired self-regulation both at the level of individual organs and the body as a whole (Corstian et al. 2008; Donati et al. 2013; Gutterman et al. 2016). At the same time, it is necessary to take into account the regional heterogeneity of the MCB due to the anatomical and topographic features of specific organs and tissues. Such morphological differences directly determine the functional characteristics of microcirculation, which is why different areas of the MCB show different sensitivity to the effects of external and internal pathogenic factors. Thus, the change in MCB reflects the formation of local foci of maladaptation and a violation of homeostasis (Braverman 1997; Segal 2005; De Backer et al. 2013; Moore et al. 2015; Dremin et al. 2017; Mizeva et al. 2017; Zherebtsov et al. 2023) having diagnostic potential in extreme physiology (Frolov et al. 2025) and stress physiology (Dunaev et al. 2014). In the field of space physiology and medicine, the diagnosis of the functional state of the MCB opens up new diagnostic possibilities for assessing the individual body's response to space flight factors, both in their modeling and in real space (Segal 2005; Dunaev et al. 2024). MATERIALS AND METHODS Research design The research was conducted at the NEK in the Scientific Research Center of the Russian Federation – IMBP RAS, which is designed to conduct scientific experiments involving humans in an artificially regulated environment, in the SIRIUS-23 isolation experiment. In isolated conditions of a hermetic facility for 366 days (2023–2024). There were 6 healthy volunteers (2 men and 4 women). Their age at the time of the start of the background studies ranged from 25 to 37 years. All the subjects received admission from the medical expert commission of the SSC RF - IMBP RAS. The conducted studies were approved by the SSC RF – IMBP RAS Bioethics Commission (Protocol No. 643 dated 07.07.2023). The cyclogram of the study (Fig. 2 ) included sessions on registration of CVS parameters at three stages: 1 session was performed before the start of isolation (the "Background" stage), 5 sessions were held inside the containment facility directly during isolation every 2–3 months, as well as 1 session after the end of isolation (the "After" stage). All studies of parameter registration took place directly in the hermetic object (Fig. 3 ) and in laboratory conditions after the end of isolation. The recording of physiological signals was carried out in a supine position. Before registration, the subjects were lying for 15 minutes to adapt to the horizontal position and environmental conditions. Next, a 10-minute recording of physiological signals was performed without volitional breathing control, followed by a 3-minute controlled breathing test at a rate of 6 breaths/min (duration of one respiratory cycle of 10 seconds, slow breathing). Research methods Analysis of heart rate variability (HRV) HRV analysis is a classic method of assessing the regulatory autonomous reactions of the body, mainly by balancing sympathetic and parasympathetic control actions, which are mainly controlled by the nervous system. We used standard HRV measurement and analysis protocols in accordance with the recommendations developed by the European Cardiological and North American Electrophysiological Societies and taking into account some methodological aspects of HRV study planning, analysis and presentation of data updated in the following decades after the publication of this document (Laborde et al. 2017 ). Study of skin blood flow An optical noninvasive diagnostic method, laser Doppler flowmetry (LDF), was used to register peripheral blood flow. The LDF method is based on probing tissues with near-infrared laser radiation and detecting light reflected back from moving red blood cells and stationary tissue structures. The recorded signal is called tissue perfusion or an indicator of blood microcirculation and is directly proportional to the rate and concentration of red blood cells in the diagnostic volume. The advantage of LDF is that it can be used to evaluate the work of local and generalized mechanisms of regulation of microcirculation. Different scientific schools distinguish from 5 to 7 frequency ranges that correspond to the following regulatory mechanisms: endothelial (0.005–0.02 Hz), due to the activity of endothelial cells, including NO-dependent endothelial regulation; neurogenic (0.02—0.046 Hz), due to neurogenic sympathetic adrenergic regulation; sensory peptidergic (0.047–0.069 Hz), reflecting the activity of sensory peptidergic fibers secreting neuropeptides and being the main component of nervous trophic tissues; myogenic or vasomotor (0.07–0.145 Hz), reflecting the oscillatory component of muscle tone of precapillaries regulating blood flow to the nutritional channel; cholinergic parasympathetic (0.16–0.18 Hz), indicating on the work of central trophotropic mechanisms and parasympathetic centers; respiratory (0.2–0.4 Hz) and cardiac (0.8–1.6 Hz) are passive mechanisms reflecting the generalized effect of respiration and heartbeat on the oscillatory activity of the microvessels, respectively (Krupatkin 2018 ). Changes in blood flow play an important role in hemodynamics. An increase in the oscillation amplitudes in the ranges responsible for vascular tone leads to a decrease in the overall resistance to blood movement. For example, increased sympathetic vasomotor activity causes vasoconstriction and increased resistance, but with a simultaneous increase in the amplitudes of blood flow fluctuations caused by the sympathetic nervous system, the oscillatory contribution to resistance decreases. Probably, such processes serve an adaptive function, smoothing out sudden changes in vascular resistance. Equipment and means of technical analysis of physiological signals To register the parameters of the autonomous regulation of the cardiovascular system, the complex for recording electrocardiograms (ECG), processing cardiointervalograms and analyzing heart rate variability "Varikard 2.8" (RAMENA LLC, Ryazan, Russia) was used. Peripheral blood flow parameters were recorded using portable laser blood microcirculation analyzers LAZMA PF (SPE LAZMA Ltd, Moscow, Russia). The devices and the layout of the sensors that register physiological signals are shown in Fig. 4 . ECG signal processing and assessment of neurovegetative regulation with HRV analysis were performed using the ISKIM-6 software (Ramena LLC, Ryazan, Russia). The received signal was edited using visual verification and manual correction of individual RR intervals and classification of QRS complexes. Abnormal complexes not caused by depolarization of the sinoatrial node were excluded from the recording. Special software Lazma (SPE LAZMA Ltd, Russia) was used to calculate the parameters of blood microcirculation. Statistical processing The Ward method was used to divide the test into groups with a fixed breathing rate. The statistical analysis was based on the method of variance analysis. The graphical interpretation shows the data arithmetic mean standard deviation. Statistical data processing was carried out in the PRISMA 8 program. Results According to the results of the 3-minute (Controlled breath) test based on HRV analysis using cluster analysis (Ward's method), the subjects were divided into groups (Fig. 5 ): Group 1–2 women and 2 men; Group 2–2 women. In controlled breathing tests, the activity and sensitivity of the vagus nerve and subcortical vascular centers are studied, including those related to the functional reserves of the autonomic nervous system. At the same time, the so-called slow heart rate waves (LF, mc 2 ) are amplified in the range of 0.15 − 0.05 Hz (with a period of 7–20 seconds). HRV spectral analysis makes it possible to assess the sensitivity and functional reserves of the corresponding regulatory links. In group 2, the activity and sensitivity of the vagus nerve and subcortical vascular center (SVC) centers, including those related to the functional reserves of the autonomic nervous system, was higher throughout the isolation experiment, starting from session 1. In group 1, we observed activation of vegetative centers from the middle (3rd session) of the isolation experiment. In this regard, in the future, we will consider the indicators of skin microhemodynamics according to the activity of the SVC (Fig. 6 ). As for the indicators of skin microhemodynamics in the assessed regions, the data obtained are shown in Fig. 7 . Changes in the in the area of the forehead skin were noted in both groups. In group 1, perfusion (I m , PU) was reduced relative to the background value during 4 study sessions. The results of the group 2 study demonstrate the wave-like nature of the dynamics of the perfusion index with an increase relative to the background study in the 1st, 2nd, 4th and 5th study sessions and a return to the background values in the 3rd session and after effect. It was also found that in group 1, endothelial tone (ET, PU) decreased in the isolation experiment, while the reduced value of the relative background value remained in the aftereffect. Unidirectional changes in basal perfusion in both groups were noted in the toe area, however, in group 2, perfusion was higher both in background studies and in isolation. In both groups, the amplitude of endothelial oscillations (A e , PU) decreases in the toe area. In addition, in group 2, the amplitude of neurogenic (A n , PU) and myogenic (A m , PU) oscillations decreases in the isolation experiment, which generally indicates a decrease in regulatory activity. In group 1, changes in these indicators are periodic. A decrease in the level of nutritional (I mn , PU) and shunt (I m_shunt , PU) blood flow in the toe area was observed during isolation. It should be noted that the proportion of nutritional blood flow in the background was higher than that of shunt blood flow, but the picture changed in the isolation experiment. This dynamic indicates that the redistribution of blood flow is more likely to occur through the shunt pathways. Discussion The main influencing factors in isolation conditions are psychophysiological stress and physical inactivity, since the gas composition of the air, temperature, humidity, microbiological conditions, physical activity, daily routine, diet and the level of fluid intake in the hermetic facility are maximally unified (Anisimova et al. 2018 ). Previously, under conditions of 120-day isolation, the presence of collagens in the urine proteome was detected, which are the basis of the extracellular matrix (Rusanov et al. 2022 ). The presence of these proteins in the analysis of the proteome may indicate changes in the characteristics of the CVS, since collagen proteins, being proteins of the extracellular matrix, are involved in the modulation of biomechanical characteristics of the CVS (rings of heart valves, heart muscle, interventricular and atrioventricular septa), as well as in the remodeling of the myocardium and blood vessels and the development of autonomic dysfunction of the CVS (Manon-Jensen et al. 2016 ). In the course of isolation studies, unique features of changes in the intensity of electrophoretic protein markers were identified, among which special attention was paid to the alpha-chain of fibrinogen and plasminogen, which perform critically important functions in hemostasis (Pastushkova et al. 2025 ). Fibrinogen is a key component of the blood coagulation system, whereas plasminogen is directly involved in the process of fibrinolysis (Castellino et al. 2005). Special attention should be paid to the fact that both of these processes are under strict control of the vascular endothelium. Endothelial cells produce a range of regulatory factors that coordinate the balance between blood clotting and fibrinolysis. It is noteworthy that the fibrinogen concentration shows significant variability, in particular, under the influence of psychoemotional stress, which is one of the isolation factors (Decamps and Rostet 2005 ). Therefore, changes in the endothelial characteristics of skin blood flow observed by us during isolation in the scalp and lower extremities may indicate a possible restructuring of vasodilatory function (Ivanov et al. 2020 ). In our study, for the first time, the change in MCB parameters depending on the type of autonomic influences in healthy subjects during simulated annual isolation was evaluated. It is shown that a long period of forced isolation and human stay in a hermetic facility leads to significant hemodynamic changes, primarily manifested in the skin of the lower extremities. The decrease in the amplitude of myogenic oscillations in the lower extremities, which we observed in isolation, led to an increase in the tone of precapillary sphincters, which regulate blood flow to the nutrient channel and, as a result, a decrease in the nutritional blood flow (Tikhomirova et al. 2018 ). In addition, an increase in the proportion of shunt blood flow occurring in isolation conditions leads to a decrease in the volume of capillary blood flow, which can lead to a deterioration in the oxygen supply to this area. Thus, in the work of Navasiolava et al. ( 2010 ), it was shown that forced inactivity in a 7-day experiment with dry immersion led to a decrease in both the overall perfusion level measured in the calf muscle area and the level of maximum achievable endothelium-dependent vasodilation. The decrease in the amplitudes of myogenic oscillations and their contribution to the total power of the spectrum can also be explained by the main influencing factors in isolation conditions on the subjects during the annual isolation experiment. CONCLUSION Thus, in conditions of isolation, we recorded signs of changes in vasomotor function and changes in the regulatory mechanisms of the cardiovascular system. It is worth noting that the fastest recovery to baseline values was observed in those volunteers in whom the activity and sensitivity of the vagus nerve and SVC centers, including those associated with the functional reserves of the autonomic nervous system, was higher throughout the isolation experiment, which indicates a greater ability of their regulatory systems to adapt to analog long-term isolation. Declarations Acknowledgements to the organizers of the SIRIUS project; all volunteers participated in this study; SIRIUS-23 crew members for conducting techniques in isolation. Author Contributions RVB, DAV, PJA conceived and designed research; PDV and POV collected data; PDV, POV, LYuI, ZhEV analyzed data; PDV, POV, LYuI, ZhEV, RVB, DAV interpreted the results; RVB, PDV, POV, PJA, LYuI, ZhEV, DAV, SVV drafted manuscript. All authors approved the final manuscript. Funding This work was supported by IBMP fundamental research program of Russian Academy of Sciences [FMFR-2024–0042] and development of the technological process for recording parameters of microcirculatory-tissue was performed within the framework of RSF grant [25-25-00546]. Data Availability No datasets were generated or analysed during the current study. Code Availability The underlying code for this study is not publicly available for proprietary reasons. Declarations All studies were carried out in accordance with the principles of biomedical ethics formulated in the 1964 Declaration of Helsinki and its later amendments and were approved by the Commission on Biomedical Ethics of the Institute of Biomedical Problems of the Russian Academy of Sciences (Moscow). Clinical Trial Number Not applicable. Consent to Publish All study participants provided their voluntary written informed consent, which they signed after potential risks and benefits, as well as the nature of the upcoming study, were explained to them. Consent to Participate Informed consent was obtained from all individual participants included in the study. Competing Interest The authors declare no competing interests. References Agaptseva, T.N., Kussmaul, A.R., Belakovskiy, M.S. et al.: Analog isolation projects: An opportunity for bench-testing technologies and products designed for long-distance space missions. Journal of Space Safety Engineering. 11 , 291-294 (2024). https://doi.org/10.1016/j.jsse.2024.03.005 Anisimova, A.S., Alexandrov, A.I., Makarova, N.E. et al.: Protein synthesis and quality control in aging. Aging. 10 , 4269-4288 (2018). https://doi.org/10.18632/aging.101721 Axpe, E., Chan, D., Abegaz, M.F. et al.: A human mission to Mars: Predicting the bone mineral density loss of astronauts. 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14:58:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":62257,"visible":true,"origin":"","legend":"\u003cp\u003eCyclogram of the research in the framework of the annual isolation experiment\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/095b8a614e0ca05f21390bfc.png"},{"id":95526813,"identity":"1e554000-a04a-4cf3-9ccd-d4009419da53","added_by":"auto","created_at":"2025-11-10 10:08:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":275318,"visible":true,"origin":"","legend":"\u003cp\u003eConducting a study in a hermetic facility (a) and the \"post-flight\" period (b) (photo by the authors)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/240efa960e1a29624d14ff17.png"},{"id":95525643,"identity":"894505e5-ac6c-45b8-92d3-a7b3be7687d5","added_by":"auto","created_at":"2025-11-10 10:05:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":315849,"visible":true,"origin":"","legend":"\u003cp\u003eDevices: Varikard 2.8 (a) and portable multimodal LASMA PF analyzers (b) and their placement for recording physiological signals (c)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/e07dc6a6ebe7b12b6e7f206e.png"},{"id":95395839,"identity":"862d1f8d-f856-4085-af08-c8ba5cdf755b","added_by":"auto","created_at":"2025-11-07 14:58:22","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":44765,"visible":true,"origin":"","legend":"\u003cp\u003eDivision into groups\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/5162b9ebc37f966a56246dd9.png"},{"id":95526431,"identity":"476cd4de-3ba4-4cfc-9617-ae38c304a457","added_by":"auto","created_at":"2025-11-10 10:06:58","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":68040,"visible":true,"origin":"","legend":"\u003cp\u003eDynamics of the LF (mc\u003csup\u003e2\u003c/sup\u003e) in the controlled breathing test\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/b4ec47fdb0298f718f084f99.png"},{"id":95395849,"identity":"b235b6c0-50b7-4654-9c1e-d5c3f19441c3","added_by":"auto","created_at":"2025-11-07 14:58:22","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":231725,"visible":true,"origin":"","legend":"\u003cp\u003eSkin blood flow indicators during isolation\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/401873d099fc67303898c614.png"},{"id":103766714,"identity":"d32a4929-eab1-40fb-a3f5-d8060425498d","added_by":"auto","created_at":"2026-03-02 16:15:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2611010,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7815651/v1/27295eb9-e9ec-40af-8051-8e875fed428c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eMicrohemodynamic Adjustments and the Type of Autinomic Regulation Under Analog Long-term Isolation Conditions\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLeaving the Earth\u0026apos;s surface, members of space crews experience not only the effects of physical factors: microgravity, radiation, noise from the equipment on the orbital station, and others (Shelhamer et al. 2020), but also face isolation, compounded by a limitation in the range of external conditions (Mircea et al. 2024). This isolation is unlike any that can be experienced on Earth. In earthly conditions, almost every one of us can break solitude by expanding our interaction with the surrounding world. Beyond the planet\u0026apos;s orbit, even excursions into open space do not expand the confines of isolation. \u003c/p\u003e\n\u003cp\u003eYuri Alekseyevich Gagarin, the first human to make an orbital flight, was in such isolation for 108 minutes. Nowadays space crew members stay in it for about 180 days. For future space travelers, this time will significantly increase and be limited by the duration of the journey into deep space.\u003c/p\u003e\n\u003cp\u003eMoreover, in the natural conditions of everyday life, each of us experiences the influence of a sufficiently broad spectrum of exogenous ecological conditions that determine adjustments (not so much homeostatic as allostatic) in the functioning of a living organism by seeking a constant equilibrium between its internal environment and the external surroundings (Sterling 2012; Goldstein 2019). In a confined orbital object, however, the range of changes in living conditions is limited to quite narrow boundaries. \u003c/p\u003e\n\u003cp\u003eSocial isolation, combined with the extremely limited area of orbital stations and living conditions, provokes a stressful state, while some familiar options for coping with it, such as the ability to take spontaneous walks, are absent among space crews. At the same time, their workload is extremely intense (Jacubowski et al. 2015), and their lifestyle and diet are very monotonous (Axpe et al. 2020).\u003c/p\u003e\n\u003cp\u003eProlonged stay of a person in a hermetic environment is accompanied by the effects of factors of a closed living volume, including: an artificial gas environment with relatively elevated levels of carbon dioxide compared to terrestrial conditions, the presence of artificial lighting, a regulated diet, a regime of physical activity, the occurrence of emergency situations, sleep deprivation, etc. Therefore, the study and analysis of the influence of multi-component conditions in an isolated volume on various systems of the human body holds significant scientific and practical importance (Orlov et al. 2023). Staying in a sealed atmosphere under controlled microclimate conditions, dietary conditions, and regulated physical activity has a pronounced effect on all physiological systems. Combined with other factors, such as elevated CO2 levels recorded aboard the International Space Station (ISS) (Fu et. al. 2019; Zhang et al. 2021) it can cause specific changes in the bodies of those performing their duties on board orbital stations, intensifying the effects of microgravity and the functional changes it causes (Goswami et al. 2021; Mircea et al. 2024).\u003c/p\u003e\n\u003cp\u003eIn recent years, a project called SIRIUS (Scientific International Research in Unique Terrestrial Station) (http://sirius.imbp.ru/ https://www.nasa.gov/humans-in-space/a-sirius-international-isolation-study/) has been implemented in Russia, consisting of a series of isolation experiments (4, 8, and 12 months) \u0026ndash; an analog project for a lunar mission. In the United States, the CHAPEA (Crew Health and Performance Exploration Analog) project serves as an analog for a Mars mission (https://www.nasa.gov/humans-in-space/chapea/).\u003c/p\u003e\n\u003cp\u003eThe global research objectives of these isolation projects are related to studying the constraints experienced during long space flights, including limitations on communication and resources available to the crew, as well as equipment failures and other emergencies, the likelihood of which increases with greater distance from low Earth orbit (LEO) (Belakovskiy et al. 2011; Orlov et al. 2015; Gushchin et al. 2019). \u003c/p\u003e\n\u003cp\u003eThe effectiveness of various resource management strategies such as food systems, waste disposal, and water purification in isolated environments is experimentally evaluated (Baranov et al. 2021; Xu et al. 2024).\u003c/p\u003e\n\u003cp\u003eIn addition, the possibilities of potential conflicts and strategies for effective cooperation are assessed. Researchers are studying the psychological impact of isolation on small groups and the individual included in them, assessing the emotional state, cognitive functions and mechanisms of overcoming psychosocial deprivation (Plomariti et al. 2022; Ushakov et al. 2012). \u003c/p\u003e\n\u003cp\u003eUndoubtedly, an important aspect of isolation projects is research on how isolation affects physical health, including basic physiological processes and their control mechanisms, as well as the development of crew selection and counter-measures, including medical ones, to help reduce the negative effects of isolation during future real-world space missions (Fedyay et al. 2023).\u003c/p\u003e\n\u003cp\u003eHermetic facilities are used for insulation projects, which make it possible to isolate volunteers for various periods of time in controlled environmental conditions: NEK (Ground-based Experimental Complex, IMBP, Russia) and HERA (Human Exploration Research Analog, NASA, USA), Yuegong-1 (Moon Palace, 月宫一号China). \u003c/p\u003e\n\u003cp\u003eThe NEK, where the SIRIUS project was conducted, is located on the territory of the IMBP RAS. It is a complex engineering facility (Fig. 1), consisting of interconnected multifunctional experimental modules:\u003c/p\u003e\n\u003cp\u003e- small landing module (volume 50 m\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n\u003cp\u003e- medical module (volume 100 m\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n\u003cp\u003e- habitable module: command cabin, private cabins, dining room, wardroom (volume 150 m\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n\u003cp\u003e- warehouse module: storage, greenhouse, gym (volume 250 m\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n\u003cp\u003e- virtual simulator of the planet\u0026rsquo;s surface.\u003c/p\u003e\n\u003cp\u003eThe NEK life support system is equipped with autonomous ventilation and air conditioning systems, water supply, sewerage, electricity, and many others. Complex engineering communications form and maintain a habitat with preset parameters, isolating the crew from the environment and simulating the main factors of real space flight, with the exception of weightlessness and radiation exposure (Agaptseva et al. 2024).\u003c/p\u003e\n\u003cp\u003eOur research scope in the SIRIUS project was related to the study of autonomic regulation and the functional state of the microcirculatory bed of the skin in healthy subjects during stay in a hermetic facility according to the scenario of an orbital flight to the Moon.\u003c/p\u003e\n\u003cp\u003eIn any extreme conditions, the body needs stability of the functions of the cardiovascular system (CVS) as one of the most important physiological systems that implements the possibility of adaptive changes (Goswami et al.2021). And, as has been shown, including in space flights, this is ensured by regulatory mechanisms (Baevsky et al. 2011; Otsuka et al. 2022).\u003c/p\u003e\n\u003cp\u003eAdaptive changes in the blood flow regulation system affect all structural and functional components of the CVS. The microcirculatory bloodstream (MCB), at the level of which the gas transportation and exchange function is realized, is the final link of these processes. \u003c/p\u003e\n\u003cp\u003eThe human body\u0026apos;s CVS performs a number of life-supporting functions, including transporting nutrients and oxygen to cells. In this regard, the MCB of the cardiovascular system, including arterioles, capillaries, arteriovenular anastomoses and venules, is of particular diagnostic interest. MCB directly provides transcapillary diffusion of oxygen and carbon dioxide, the general trophism of peripheral tissue structures of the body, as well as their adaptive stability under changing endogenous or exogenous conditions (Cracowski and Roustit 2020).\u003c/p\u003e\n\u003cp\u003eA diagnostically significant feature of the MCB is its dynamic nature, as well as temporal and spatial functional heterogeneity. This makes the MCB the first link reflecting disturbances in the system of protective and adaptive reactions aimed at restoring impaired self-regulation both at the level of individual organs and the body as a whole (Corstian et al. 2008; Donati et al. 2013; Gutterman et al. 2016).\u003c/p\u003e\n\u003cp\u003eAt the same time, it is necessary to take into account the regional heterogeneity of the MCB due to the anatomical and topographic features of specific organs and tissues. Such morphological differences directly determine the functional characteristics of microcirculation, which is why different areas of the MCB show different sensitivity to the effects of external and internal pathogenic factors. Thus, the change in MCB reflects the formation of local foci of maladaptation and a violation of homeostasis (Braverman 1997; Segal 2005; De Backer et al. 2013; Moore et al. 2015; Dremin et al. 2017; Mizeva et al. 2017; Zherebtsov et al. 2023) having diagnostic potential in extreme physiology (Frolov et al. 2025) and stress physiology (Dunaev et al. 2014). \u003c/p\u003e\n\u003cp\u003eIn the field of space physiology and medicine, the diagnosis of the functional state of the MCB opens up new diagnostic possibilities for assessing the individual body\u0026apos;s response to space flight factors, both in their modeling and in real space (Segal 2005; Dunaev et al. 2024).\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eResearch design\u003c/h2\u003e\u003cp\u003eThe research was conducted at the NEK in the Scientific Research Center of the Russian Federation \u0026ndash; IMBP RAS, which is designed to conduct scientific experiments involving humans in an artificially regulated environment, in the SIRIUS-23 isolation experiment. In isolated conditions of a hermetic facility for 366 days (2023\u0026ndash;2024).\u003c/p\u003e\u003cp\u003eThere were 6 healthy volunteers (2 men and 4 women). Their age at the time of the start of the background studies ranged from 25 to 37 years. All the subjects received admission from the medical expert commission of the SSC RF - IMBP RAS. The conducted studies were approved by the SSC RF \u0026ndash; IMBP RAS Bioethics Commission (Protocol No. 643 dated 07.07.2023).\u003c/p\u003e\u003cp\u003eThe cyclogram of the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) included sessions on registration of CVS parameters at three stages: 1 session was performed before the start of isolation (the \"Background\" stage), 5 sessions were held inside the containment facility directly during isolation every 2\u0026ndash;3 months, as well as 1 session after the end of isolation (the \"After\" stage).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAll studies of parameter registration took place directly in the hermetic object (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and in laboratory conditions after the end of isolation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe recording of physiological signals was carried out in a supine position. Before registration, the subjects were lying for 15 minutes to adapt to the horizontal position and environmental conditions. Next, a 10-minute recording of physiological signals was performed without volitional breathing control, followed by a 3-minute controlled breathing test at a rate of 6 breaths/min (duration of one respiratory cycle of 10 seconds, slow breathing).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eResearch methods\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eAnalysis of heart rate variability (HRV)\u003c/h2\u003e\u003cp\u003eHRV analysis is a classic method of assessing the regulatory autonomous reactions of the body, mainly by balancing sympathetic and parasympathetic control actions, which are mainly controlled by the nervous system. We used standard HRV measurement and analysis protocols in accordance with the recommendations developed by the European Cardiological and North American Electrophysiological Societies and taking into account some methodological aspects of HRV study planning, analysis and presentation of data updated in the following decades after the publication of this document (Laborde et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy of skin blood flow\u003c/h3\u003e\n\u003cp\u003eAn optical noninvasive diagnostic method, laser Doppler flowmetry (LDF), was used to register peripheral blood flow. The LDF method is based on probing tissues with near-infrared laser radiation and detecting light reflected back from moving red blood cells and stationary tissue structures. The recorded signal is called tissue perfusion or an indicator of blood microcirculation and is directly proportional to the rate and concentration of red blood cells in the diagnostic volume. The advantage of LDF is that it can be used to evaluate the work of local and generalized mechanisms of regulation of microcirculation. Different scientific schools distinguish from 5 to 7 frequency ranges that correspond to the following regulatory mechanisms: endothelial (0.005\u0026ndash;0.02 Hz), due to the activity of endothelial cells, including NO-dependent endothelial regulation; neurogenic (0.02\u0026mdash;0.046 Hz), due to neurogenic sympathetic adrenergic regulation; sensory peptidergic (0.047\u0026ndash;0.069 Hz), reflecting the activity of sensory peptidergic fibers secreting neuropeptides and being the main component of nervous trophic tissues; myogenic or vasomotor (0.07\u0026ndash;0.145 Hz), reflecting the oscillatory component of muscle tone of precapillaries regulating blood flow to the nutritional channel; cholinergic parasympathetic (0.16\u0026ndash;0.18 Hz), indicating on the work of central trophotropic mechanisms and parasympathetic centers; respiratory (0.2\u0026ndash;0.4 Hz) and cardiac (0.8\u0026ndash;1.6 Hz) are passive mechanisms reflecting the generalized effect of respiration and heartbeat on the oscillatory activity of the microvessels, respectively (Krupatkin \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Changes in blood flow play an important role in hemodynamics. An increase in the oscillation amplitudes in the ranges responsible for vascular tone leads to a decrease in the overall resistance to blood movement. For example, increased sympathetic vasomotor activity causes vasoconstriction and increased resistance, but with a simultaneous increase in the amplitudes of blood flow fluctuations caused by the sympathetic nervous system, the oscillatory contribution to resistance decreases. Probably, such processes serve an adaptive function, smoothing out sudden changes in vascular resistance.\u003c/p\u003e\n\u003ch3\u003eEquipment and means of technical analysis of physiological signals\u003c/h3\u003e\n\u003cp\u003eTo register the parameters of the autonomous regulation of the cardiovascular system, the complex for recording electrocardiograms (ECG), processing cardiointervalograms and analyzing heart rate variability \"Varikard 2.8\" (RAMENA LLC, Ryazan, Russia) was used. Peripheral blood flow parameters were recorded using portable laser blood microcirculation analyzers LAZMA PF (SPE LAZMA Ltd, Moscow, Russia). The devices and the layout of the sensors that register physiological signals are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eECG signal processing and assessment of neurovegetative regulation with HRV analysis were performed using the ISKIM-6 software (Ramena LLC, Ryazan, Russia). The received signal was edited using visual verification and manual correction of individual RR intervals and classification of QRS complexes. Abnormal complexes not caused by depolarization of the sinoatrial node were excluded from the recording.\u003c/p\u003e\u003cp\u003eSpecial software Lazma (SPE LAZMA Ltd, Russia) was used to calculate the parameters of blood microcirculation.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical processing\u003c/h2\u003e\u003cp\u003eThe Ward method was used to divide the test into groups with a fixed breathing rate. The statistical analysis was based on the method of variance analysis. The graphical interpretation shows the data arithmetic mean standard deviation. Statistical data processing was carried out in the PRISMA 8 program.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAccording to the results of the 3-minute (Controlled breath) test based on HRV analysis using cluster analysis (Ward's method), the subjects were divided into groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e): Group 1\u0026ndash;2 women and 2 men; Group 2\u0026ndash;2 women.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn controlled breathing tests, the activity and sensitivity of the vagus nerve and subcortical vascular centers are studied, including those related to the functional reserves of the autonomic nervous system. At the same time, the so-called slow heart rate waves (LF, mc\u003csup\u003e2\u003c/sup\u003e) are amplified in the range of 0.15\u0026thinsp;\u0026minus;\u0026thinsp;0.05 Hz (with a period of 7\u0026ndash;20 seconds). HRV spectral analysis makes it possible to assess the sensitivity and functional reserves of the corresponding regulatory links.\u003c/p\u003e\u003cp\u003eIn group 2, the activity and sensitivity of the vagus nerve and subcortical vascular center (SVC) centers, including those related to the functional reserves of the autonomic nervous system, was higher throughout the isolation experiment, starting from session 1. In group 1, we observed activation of vegetative centers from the middle (3rd session) of the isolation experiment. In this regard, in the future, we will consider the indicators of skin microhemodynamics according to the activity of the SVC (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAs for the indicators of skin microhemodynamics in the assessed regions, the data obtained are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. Changes in the in the area of the forehead skin were noted in both groups. In group 1, perfusion (I\u003csub\u003em\u003c/sub\u003e, PU) was reduced relative to the background value during 4 study sessions. The results of the group 2 study demonstrate the wave-like nature of the dynamics of the perfusion index with an increase relative to the background study in the 1st, 2nd, 4th and 5th study sessions and a return to the background values in the 3rd session and after effect.\u003c/p\u003e\u003cp\u003eIt was also found that in group 1, endothelial tone (ET, PU) decreased in the isolation experiment, while the reduced value of the relative background value remained in the aftereffect. Unidirectional changes in basal perfusion in both groups were noted in the toe area, however, in group 2, perfusion was higher both in background studies and in isolation. In both groups, the amplitude of endothelial oscillations (A\u003csub\u003ee\u003c/sub\u003e, PU) decreases in the toe area. In addition, in group 2, the amplitude of neurogenic (A\u003csub\u003en\u003c/sub\u003e, PU) and myogenic (A\u003csub\u003em\u003c/sub\u003e, PU) oscillations decreases in the isolation experiment, which generally indicates a decrease in regulatory activity. In group 1, changes in these indicators are periodic.\u003c/p\u003e\u003cp\u003eA decrease in the level of nutritional (I\u003csub\u003emn\u003c/sub\u003e, PU) and shunt (I\u003csub\u003em_shunt\u003c/sub\u003e, PU) blood flow in the toe area was observed during isolation. It should be noted that the proportion of nutritional blood flow in the background was higher than that of shunt blood flow, but the picture changed in the isolation experiment. This dynamic indicates that the redistribution of blood flow is more likely to occur through the shunt pathways.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main influencing factors in isolation conditions are psychophysiological stress and physical inactivity, since the gas composition of the air, temperature, humidity, microbiological conditions, physical activity, daily routine, diet and the level of fluid intake in the hermetic facility are maximally unified (Anisimova et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePreviously, under conditions of 120-day isolation, the presence of collagens in the urine proteome was detected, which are the basis of the extracellular matrix (Rusanov et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The presence of these proteins in the analysis of the proteome may indicate changes in the characteristics of the CVS, since collagen proteins, being proteins of the extracellular matrix, are involved in the modulation of biomechanical characteristics of the CVS (rings of heart valves, heart muscle, interventricular and atrioventricular septa), as well as in the remodeling of the myocardium and blood vessels and the development of autonomic dysfunction of the CVS (Manon-Jensen et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the course of isolation studies, unique features of changes in the intensity of electrophoretic protein markers were identified, among which special attention was paid to the alpha-chain of fibrinogen and plasminogen, which perform critically important functions in hemostasis (Pastushkova et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Fibrinogen is a key component of the blood coagulation system, whereas plasminogen is directly involved in the process of fibrinolysis (Castellino et al. 2005). Special attention should be paid to the fact that both of these processes are under strict control of the vascular endothelium. Endothelial cells produce a range of regulatory factors that coordinate the balance between blood clotting and fibrinolysis. It is noteworthy that the fibrinogen concentration shows significant variability, in particular, under the influence of psychoemotional stress, which is one of the isolation factors (Decamps and Rostet \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Therefore, changes in the endothelial characteristics of skin blood flow observed by us during isolation in the scalp and lower extremities may indicate a possible restructuring of vasodilatory function (Ivanov et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn our study, for the first time, the change in MCB parameters depending on the type of autonomic influences in healthy subjects during simulated annual isolation was evaluated. It is shown that a long period of forced isolation and human stay in a hermetic facility leads to significant hemodynamic changes, primarily manifested in the skin of the lower extremities. The decrease in the amplitude of myogenic oscillations in the lower extremities, which we observed in isolation, led to an increase in the tone of precapillary sphincters, which regulate blood flow to the nutrient channel and, as a result, a decrease in the nutritional blood flow (Tikhomirova et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). In addition, an increase in the proportion of shunt blood flow occurring in isolation conditions leads to a decrease in the volume of capillary blood flow, which can lead to a deterioration in the oxygen supply to this area.\u003c/p\u003e\u003cp\u003eThus, in the work of Navasiolava et al. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), it was shown that forced inactivity in a 7-day experiment with dry immersion led to a decrease in both the overall perfusion level measured in the calf muscle area and the level of maximum achievable endothelium-dependent vasodilation. The decrease in the amplitudes of myogenic oscillations and their contribution to the total power of the spectrum can also be explained by the main influencing factors in isolation conditions on the subjects during the annual isolation experiment.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThus, in conditions of isolation, we recorded signs of changes in vasomotor function and changes in the regulatory mechanisms of the cardiovascular system. It is worth noting that the fastest recovery to baseline values was observed in those volunteers in whom the activity and sensitivity of the vagus nerve and SVC centers, including those associated with the functional reserves of the autonomic nervous system, was higher throughout the isolation experiment, which indicates a greater ability of their regulatory systems to adapt to analog long-term isolation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eto the organizers of the SIRIUS project; all volunteers participated in this study; SIRIUS-23 crew members for conducting techniques in isolation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRVB, DAV, PJA conceived and designed research; PDV and POV collected data; PDV, POV, LYuI, ZhEV analyzed data; PDV, POV, LYuI, ZhEV, RVB, DAV interpreted the results; RVB, PDV, POV, PJA, LYuI, ZhEV, DAV, SVV drafted manuscript. All authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis work was supported by IBMP fundamental research program of Russian Academy of Sciences [FMFR-2024–0042] and\u0026nbsp;development of the technological process for recording parameters of microcirculatory-tissue was performed within the framework of RSF grant [25-25-00546].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u0026nbsp;\u003c/strong\u003eThe underlying code for this study is not publicly available for proprietary reasons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u0026nbsp;\u003c/strong\u003eAll studies were carried out in accordance with the principles of biomedical ethics formulated in the 1964 Declaration of Helsinki and its later amendments and were approved by the Commission on Biomedical Ethics of the Institute of Biomedical Problems of the Russian Academy of Sciences (Moscow).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial\u0026nbsp;\u003c/strong\u003eNumber Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Consent to Publish\u0026nbsp;\u003c/strong\u003eAll study participants provided their voluntary written informed consent, which they signed after potential risks and benefits, as well as the nature of the upcoming study, were explained to them.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Consent to Participate\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Competing Interest\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAgaptseva, T.N., Kussmaul, A.R., Belakovskiy, M.S. et al.: Analog isolation projects: An opportunity for bench-testing technologies and products designed for long-distance space missions. 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IEEE Trans Biomed Eng. \u003cstrong\u003e70\u003c/strong\u003e, 3073-3081 (2023). https://doi.org/10.1109/TBME.2023.3275654\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"microgravity-science-and-technology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mgst","sideBox":"Learn more about [Microgravity Science and Technology](http://link.springer.com/journal/12215)","snPcode":"12217","submissionUrl":"https://submission.nature.com/new-submission/12217/3","title":"Microgravity Science and Technology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Isolation conditions, Cardiovascular system, Autonomic regulation, HRV analysis, Microhemodynamics, Laser Doppler flowmetry","lastPublishedDoi":"10.21203/rs.3.rs-7815651/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7815651/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study investigates microhemodynamic and autonomic regulation changes during long-term isolation in a 366-day SIRIUS-23 experiment involving 6 healthy volunteers (2 men and 4 women, aged 25\u0026ndash;37 years). Heart rate variability analysis and laser Doppler flowmetry were used to assess cardiovascular system responses before, during, and after isolation. Volunteers demonstrated distinct autonomic regulation patterns, dividing into two groups based on vagal tone and vascular center activity. Group 2 showed consistently higher autonomic function throughout the experiment. Microcirculation parameters revealed decreased perfusion in the forehead area for Group 1 and fluctuating dynamics for Group 2. Both groups exhibited endothelial tone reduction and altered blood flow distribution in the toe area with increased shunt flow. Prolonged isolation significantly affects microhemodynamics and autonomic regulation. Individuals with higher vagal tone demonstrated better adaptation. These findings contribute to understanding physiological responses to long-term confinement and have implications for space mission medical support.\u003c/p\u003e","manuscriptTitle":"Microhemodynamic Adjustments and the Type of Autinomic Regulation Under Analog Long-term Isolation Conditions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-07 14:58:17","doi":"10.21203/rs.3.rs-7815651/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-27T16:43:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T09:27:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296036549300370992455608410851709961108","date":"2025-11-15T15:16:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124490394359354562032351861109759046373","date":"2025-11-05T10:21:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-28T10:34:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-20T13:42:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-20T13:41:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"Microgravity Science and Technology","date":"2025-10-09T09:19:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"microgravity-science-and-technology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mgst","sideBox":"Learn more about [Microgravity Science and Technology](http://link.springer.com/journal/12215)","snPcode":"12217","submissionUrl":"https://submission.nature.com/new-submission/12217/3","title":"Microgravity Science and Technology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"72d36f5c-9c07-4a7e-9e32-965e969b8d26","owner":[],"postedDate":"November 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:13:43+00:00","versionOfRecord":{"articleIdentity":"rs-7815651","link":"https://doi.org/10.1007/s12217-026-10241-8","journal":{"identity":"microgravity-science-and-technology","isVorOnly":false,"title":"Microgravity Science and Technology"},"publishedOn":"2026-02-28 15:59:53","publishedOnDateReadable":"February 28th, 2026"},"versionCreatedAt":"2025-11-07 14:58:17","video":"","vorDoi":"10.1007/s12217-026-10241-8","vorDoiUrl":"https://doi.org/10.1007/s12217-026-10241-8","workflowStages":[]},"version":"v1","identity":"rs-7815651","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7815651","identity":"rs-7815651","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}