Introduction The aim of this study was to characterize infradian rhythms in heart rate and blood pressure, as well as investigate potential synchronization of these parameters among participants in the Mars 500 study. This study involved a 520-day simulated mission to Mars, during which six crew members were confined for the entire duration of the experiment. Methods The study involved daily measurements of blood pressure and heart rate, taken in the morning and evening for each participant. Mean differences were analyzed using a mixed model design, considering journey stage and time of day as fixed factors, and participant as a random factor. The Lomb-Scargle periodogram was used to identify rhythmic patterns in the data. Significant rhythms were described by fitting a cosine curve using a cosinor model. The level of synchronization between participants' measurements was assessed by analyzing signal pairs using the Hilbert transform. Phase differences were measured in one-month bins using the gamma parameter. Surrogate data was employed for comparison with the observed data. Gamma differences between bins were evaluated using a mixed model design. Results All signals showed significant changes over time, and most participants exhibited at least one significant infradian rhythm in the analyzed variables. The primary peaks varied between participants and variables, ranging from 22 days to 520 days. Interestingly, there was a consistent period of 173 days observed in the evening heart rate across all participants. Regarding synchronization, the gamma values of evening heart rate differed from surrogate data in all stages, except during the middle part of the mission. Discussion The primary finding of this study is the identification of significant infradian rhythms in cardiovascular variables, specifically in evening heart rate, with a shared and synchronized period of 173 days among participants. We propose that affective changes associated with different stages of the mission, along with the cohesive functioning of the crew as a unit, may contribute to these variations.

Background: Failure to activate autonomic neural and hormonal reflex mechanisms could result in orthostatic hypotension. Patients with orthostatic hypotension often experience symptoms of cerebral hypoperfusion, including syncope. The purpose of this study was to investigate the haemodynamic characteristics of patients with orthostatic hypotension and the factors affecting blood pressure regulation. Methods : This retrospective study enrolled 45 patients who were diagnosed with typical orthostatic hypotension by the head-up tilt test at Beijing Tiantan Hospital, Capital Medical University from June 2019 to December 2020. Changes in haemodynamic parameters in these patients were compared in the supine and tilted upright positions. Results : For all patients, haemodynamic parameters in the supine and tilted upright positions were compared, and systolic blood pressure, diastolic blood pressure, mean blood pressure, cardiac output and stroke volume were all significantly decreased per minute. Heart rate significantly increased per minute, but systemic vascular resistance did not significantly change. The absolute value, percentage and rate of increases in heart rate and the absolute value, percentage and rate of decreases in stroke volume from the supine to the titled upright position were significantly lower in patients 60 years and older than in patients under 60 years old. Linear regression analyses found that the changes in heart rate, stroke volume and systemic vascular resistance were related to changes in systolic blood pressure, while the changes in stroke volume and systemic vascular resistance had more important effects on systolic blood pressure. Conclusions : In patients with orthostatic hypotension, we observed no significant increase in systemic vascular resistance from the supine position to the tilted upright position. Nevertheless, an increase in systemic vascular resistance had a significant impact on the maintenance of systolic blood pressure. In addition, in orthostatic hypotension patients younger than 60 years of age, heart rate increased while stroke volume decreased significantly after tilting upright compared with orthostatic hypotension patients older than 60 years of age and older.

Objective To study whether the head-up tilt test(HUTT) with an appropriate increased tilt angle can produce similar hemodynamic effects during shortened tilt duration with the effects of traditional lower angle tilt protocol.Methods Twenty-two healthy volunteers participated in this study.Two different drug-free tilt test protocols were used.First,tilt test was performed with the 60° standard protocol (60SP group) for 45 min,after 14 days,the second tilt test was performed with the 75° short duration protocol for 20 min (75SD group).Noninvasive beat-to-beat blood pressure was measured with an infrared finger photoplethysmograph during the two tilt test protocols,while heart rate (HR),blood pressure,stroke volume(SV),cardiac output(CO),systemic vascular resistance(SVR) and baroreflex sensitivity(BRS) were estimated.Results No significant difference was found in HR,MAP,SV,CO,SVR and BRS between the two tilt tests with different protocols in the supine position before tilt.No significant hemodynamic change was found in the initial responses to the two different tilt angles.In the evolution of up-right position,only a significant difference could be found in SV (P=0.01) between 60SP for 45 min and 75SD for 20 min around all hemodynamic parameters.Conclusion It is suggested that most hemodynamic responses to higher tilt angle with shorten time duration are equal to the effects of traditional lower tilt angle with longer time duration.The tilt test protocol with higher angle and shorten time duration will save the diagnostic time for clinical application with the similar effectiveness.

During Antarctic isolation personnel are exposed to extreme photoperiods. A frequent observation is a sleep onset phase delay during winter. It is not known if, as a result, daytime sleeping in the form of naps increases. We sought to assess sleep patterns - with focus on daytime sleeping - and alertness in a Latin American crew overwintering in Argentine Antarctic station Belgrano II. Measurements were collected in 13 males during March, May, July, September and November, and included actigraphy and psychomotor vigilance tasks. Sleep duration significantly decreased during winter. A total of eight participants took at least one weekly nap across all measurement points. During winter, the nap onset was delayed, its duration increased and its efficiency improved. We observed a significant effect of seasonality in the association of evening alertness with sleep onset. Our results replicate previous findings regarding sleep during overwintering in Antarctica, adding the description of the role of napping and the report of a possible modulatory effect of seasonality in the relation between sleep and alertness. Napping should be considered as an important factor in the scheduling of activities of multicultural crews that participate in Antarctica.

In psychology, the use of intensive longitudinal data has steeply increased during the past decade. As a result, studying temporal dependencies in such data with autoregressive modeling is becoming common practice. However, standard autoregressive models are often suboptimal as they assume that parameters are time-invariant. This is problematic if changing dynamics (e.g., changes in the temporal dependency of a process) govern the time series. Often a change in the process, such as emotional well-being during therapy, is the very reason why it is interesting and important to study psychological dynamics. As a result, there is a need for an easily applicable method for studying such nonstationary processes that result from changing dynamics. In this article we present such a tool: the semiparametric TV-AR model. We show with a simulation study and an empirical application that the TV-AR model can approximate nonstationary processes well if there are at least 100 time points available and no unknown abrupt changes in the data. Notably, no prior knowledge of the processes that drive change in the dynamic structure is necessary. We conclude that the TV-AR model has significant potential for studying changing dynamics in psychology.

Objective To assess the determinants of hypotension during drug - free and Nitroglycerine (NTG)induced syncope in routine tilt table testing.Methods A total of 56 patients with neurally media-ted syncope and a positive tilt test were selected in this retrospective study.Syncope was provoked by 0.4 mg sublingual NTG in 29 patients,administered in the 60°head-up tilt position,while syncope was pro-voked by passive tilt alone in other 27 patients.No invasive finger arterial pressure was monitored continu-ously and hemodynamic parameters were computed from the pressure pulsations.Results The use of NTG did not affect circulatory patterns precipitating a vasovagal response.Hypotension during syncope was me-diated by a marked drop in cardiac output,while systemic vascular resistance was well maintained.Conclu-sion In routine tilt testing,hypotension is cardiac output-mediated the mechanism of which appears inde-pendent on the use of sublingual NTG.

Purpose Weightlessness has a well-known effect on the autonomic control of the cardiovascular system. With future missions to Mars in mind, it is important to know what the effect of partial gravity is on the human body. We aim to study the autonomic response of the cardiovascular system to partial gravity levels, as present on the Moon and on Mars, during parabolic flight. Methods ECG and blood pressure were continuously recorded during parabolic flight. A temporal analysis of blood pressure and heart rate to changing gravity was conducted to study the dynamic response. In addition, cardiovascular autonomic control was quantified by means of heart rate (HR) and blood pressure (BP) variability measures. Results Zero and lunar gravity presented a biphasic cardiovascular response, while a triphasic response was noted during martian gravity. Heart rate and blood pressure are positively correlated with gravity, while the general variability of HR and BP, as well as vagal indices showed negative correlations with increasing gravity. However, the increase in vagal modulation during weightlessness is not in proportion when compared to the increase during partial gravity. Conclusions Correlations were found between the gravity level and modulations in the autonomic nervous system during parabolic flight. Nevertheless, with future Mars missions in mind, more studies are needed to use these findings to develop appropriate countermeasures.

Spaceflight and head-down bed rest (HDBR) can induce the orthostatic intolerance (OI); the mechanisms remain to be clarified. The aim of this study was to determine whether or not OI after HDBR relates to the degree of autonomic cardiovascular adaptation. Fourteen volunteers were enrolled for 60 days of HDBR. A head-up tilt test (HUTT) was performed before and after HDBR. Our data revealed that, in all nonfainters, there was a progressive increase in heart rate over the course of HDBR, which remained higher until 12 days of recovery. The mean arterial pressure gradually increased until day 56 of HDBR and returned to baseline after 12 days of recovery. Respiratory sinus arrhythmia and baroreflex sensitivity decreased during HDBR and remained suppressed until 12 days of recovery. Low-frequency power of systolic arterial pressure increased during HDBR and remained elevated during recovery. Three subjects fainted during the HUTT after HDBR, in which systemic vascular resistance did not increase and remained lower until syncope. None of the circulatory patterns significantly differed between the fainters and the nonfainters at any time point. In conclusion, our data indicate that the impaired orthostatic tolerance after HDBR could not be distinguished by estimation of normal hemodynamic and/or neurocardiac data.

Purpose The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. Methods Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. Results Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. Conclusion Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.

Purpose The objective was to check if 520 days in confinement (MARS 500), may affect the main peripheral arterial diameter and wall thickness and the main vein size. Method Common carotid (CC) femoral artery (FA) portal vein (PV), jugular (JG), femoral vein (FV) and tibial vein were assessed during MARS 500 by echography, performed by the subjects. A hand free volumic echographic capture method and a delayed 3D reconstruction software developed by our lab were used for collecting and measuring the vascular parameters. Results During the MARS 500 experiment the subjects performed 6 sessions among which 80% of the echographic data were of sufficient quality to be processed. No significant change was found for the Common carotid, Jugular vein, femoral artery, femoral vein, portal vein, and tibial vein diameter. CC and FA IMT (intima media thickness) were found significantly increased (14% to 28% P<0.05) in all the 6 subjects, during the confinement period and also at +2 days after the confinement period, but there was no significant difference 6 month later compare to pre MARS 500. Conclusion The experiment confirmed that even untrained to performing echography the subjects were able to capture enough echographic data to reconstruct the vessel image from which the parameters were measured. The increase in both CC and FA IMT should be in relation with the stress generated by the confined environment or absence of solar radiation, as there was no change in gravity, temperature and air in the MARS 500 module, and minor changes in physical exercise and nutrition.

André Aubert, Yoann Bataille, Ann Belmans, Edouard Benit, Guy Berkenboom, Olivier Bertrand, Christian Brohet, Pedro Brugada, Werner Budts*, Jean-Jacques Cassiman, Jean-Paul Chapelle, Marc Claeys, Denis Clement, Laurent Davin, Guy De Backer, Julie De Backer, Bart De Geest*, Johan De Sutter, Daniel De Wolf, Chantal Dedobbeleer, Jo Defraigne, Victoria Delgado, Paul Dendale, Jo Dens, Walter Desmet, Chantal Dessy, Erwan Donal*, Steven Droogmans, Walter Droogné, Steven Droopmans, Jean Ducobu, Mathias Dupont, Hugo Ector*, Joris Ector, Alain Friart, Olivier Gach, Peter Geelen, Claude Hanet, Hein Heidbüchel, Paul Herijgers, Marie-Christine Herregods, Etienne Hoffer, Luc Jordeans, Philippe Kolh, Jean-Marie Krzesinski, Henri Kulbertus*, Marcus Lance (The Netherlands), Patrizio Lancellotti, Jean-Benoît le Polain de Waroux, Victor Legrand*, Georges Mairesse*, Martial Massin, Marie-Paule Merville, Luc Missault, Robert Naeije, Alain Nchimi, Cécile Oury, Bernard Paelinck, Agnès Pasquet*, Willy Peetermans, Alexandre Persu, Eugenio Picano (Italy), Luc Piérard*, Suzanne Pourbaix, Tony Reybrouck, Marie-Christine Seghaye, Paul Sergeant*, Peter Sinnaeve, Muriel Sprynger*, Lutgarde Thijs, Pierre Troisfontaines, Philippe Unger, Guy Van Camp, Nico Van De Veire*, Frans Van de Werf, Aleyde Van Eynde, Walter Van Mieghem*, Eric Van Wijngaerden, Tom Vandendriessche, Thierry Verbeet, Peter Verhamme, Jos Vermylen, Jens-Uwe Voigt, Francis Wellens.

Slow breathing is widely applied to improve symptoms of hyperarousal, but it is unknown whether its beneficial effects relate to the reduction in respiration rate per se, or, to a lower inhalation/exhalation (i/e) ratio. The present study examined the effects of four ventilatory patterns on heart rate variability and self-reported dimensions of relaxation. Thirty participants were instructed to breathe at 6 or 12 breaths/min, and with an i/e ratio of 0.42 or 2.33. Participants reported increased relaxation, stress reduction, mindfulness and positive energy when breathing with the low compared to the high i/e ratio. A lower compared to a higher respiration rate was associated only with an increased score on positive energy. A low i/e ratio was also associated with more power in the high frequency component of heart rate variability, but only for the slow breathing pattern. Our results show that i/e ratio is an important modulator for the autonomic and subjective effects of instructed ventilatory patterns.

Background Spaceflight causes changes in the cardiovascular control system. The aim of this study was to evaluate postflight recovery of linear and nonlinear neural markers of heart rate modulation, with a special focus on day-night variations. Material/Methods Twenty-four-hour Holter ECG recordings were obtained in 8 astronauts participating in space missions aboard the International Space Station (ISS). Data recording was performed 1 month before launch, and 5 and 30 days after return to Earth from short- and long-term flights. Cardiovascular control was inferred from linear and nonlinear heart rate variability (HRV) parameters, separately during 2-hour day and 2-hour night recordings. Results No remarkable differences were found in the postflight recovery between astronauts from short- and long-duration spaceflights. Five days after return to Earth, vagal modulation was significantly decreased compared to the preflight condition (day: p=0.001; night: p=0.019), while the sympathovagal balance was strongly increased, but only at night (p=0.017). A few nonlinear parameters were reduced early postflight compared to preflight values, but these were not always statistically significant. No significant differences remained after 30 days of postflight recovery. Conclusions Our results show that 5 days after return from both short- and long-duration space missions, neural mechanisms of heart rate regulation are still disturbed. After 1 month, autonomic control of heart rate recovered almost completely.

Introduction/Background Research focusing on anesthesia delivery for future interplanetary space missions is scarce, partly because no existing human model on Earth is able to reproduce the vast and specific physiological changes occurring in response to microgravity. Using the Meti Human Patient Simulator (HPS), a prospective comparative study was conducted with the objective of defining the best anesthesia protocol for space exploration missions, suitable for the drastic technical and human constraints and the altered physiological state of an astronaut. Methods Five experts in anesthesia and/or simulation were enrolled in the study. The HPS was programmed to reproduce the physiological alterations experienced by crewmembers during long-duration spaceflight, in particular the cardiovascular deconditioning. Blood volume, left and right ventricular contractility, baroreflex and systemic vascular resistance were set at levels measured in actual astronauts during long-duration spaceflight. Two general anesthesia protocols (with spontaneous ventilation and oro-tracheal intubation) were tested in two scenarios, comparing three different anesthetics (propofol, etomidate and ketamine). One of the scenarios was complicated with an additional 1000 ml haemorrhage. Results Mean arterial pressure 60 seconds after induction was significantly lower in the groups propofol (mean +/- SD: 56.1 +/- 4.5 mmHg) and etomidate (54.4 +/- 3.5 mmHg) compared to the group ketamine (72.3 +/- 4.7 mmHg, p<0.0003). The groups propofol and etomidate required significantly more intravenous fluids (respectively 1450 +/- 598 mL and 1400 +/- 658 mL) compared to the group ketamine (800 +/- 349 mL, p<0.01). Significantly more vasoconstrictors boluses (phenylephrine) were administered in the groups propofol (2 +/- 0.44) and etomidate (2 +/- 0) compared to the group ketamine (0, p<0.01). Contrary to the propofol and etomidate groups, none of the trials in the ketamine group developed cardiovascular collapse, required large volumes of intravenous fluids nor received vasoconstrictors. Conclusion For the first time, the complex physiological and pharmacological algorithms of the HPS were used to accurately reproduce the altered physiology of an astronaut, and test the tolerance to hypovolemia and general anesthesia. The Results confirmed the superiority of ketamine in this situation, which should become the anesthetic drug of choice for the preparation of future space exploration missions. Disclosures None.

■ Marc Abramowicz, Wim Anné, André Aubert*, Ann Belmans, Edouard Benit, Guy Berkenboom, Philippe Bertrand, Jean Boland, Johan Bosmans, Christian Brohet, Pedro Brugada*, Werner Budts*, Jean-Jacques Cassiman*, Marc Claeys, Denis Clement, Bernard Cosyns, Patrick Coussement, Laurent Davin, Guy De Backer, Marc De Buyzere, Bart De Geest*, Luc De Roy, Johan De Sutter, Paul Dendaele, Jo Dens, Walter Desmet, Koen Devriendt, Steven Droogmans, Walter Droogné, Jean Ducobu, Raluca Dulghem (Romania), Hugo Ector, Joris Ector, Fabio Fernandez (Brazil), Inge Fourneau, Alain Friar, Laurence Gabriel, Olivier Gach*, Christophe Garweg, Sofie Gevaert, Thierry Gillebert, Marnix Goethals, Marc Goethals, Peter Goethals, André Gothot, Yumei Gu, Hein Heidbüchel, Paul Herijgers, Cedric Hermans, Marie-Christine Herregods*, Jean-Manuel Herzet, Etienne Hoffer, Luc Hondeghem, Peter Kayaert, Joëlle Kefer, Philippe Kolh, Jean-Marie Krzesinski, Patrizio Lancellotti*, Robert Larbuisson, Jean-Benoît Le Polain de Waroux, Victor Legrand*, Georges Mairesse*, Marcello Marci (Italy), Martial Massin*, Pascal McKeown (United Kingdom), Pierre Melon*, Luc Missault, Raoul Moreno (Spain), Marielle Morissens, Cécile Oury, Michel Ovize (France), Agnès Pasquet*, Luc Piérard, Suzanne Pourbaix, Frank Provenier, Regis Radermecker, Tony Reybrouck, José Castro Rodriguez, Raymond-Pierre Roudaut (France), Danny Schoors, Paul Sergeant*, Peter Sinnaeve, Muriel Sprynger, Jan Staessen, Kaoru Tanaka, Lutgarde Thijs, Els Troost, Hans Van Brabandt, Guy Van Camp, Nico Van De Veire, Walter Van Mieghem*, Pieter Vandervoort, Johan Vanhaecke, Luc Vanhees, Thierry Verbeet*, Peter Verhamme and Jos Vermylen.

Validation of Anesthesia Protocols Designed for Space Exploration Missions using a Human Patient Simulator (Submission #1156) Matthieu Komorowski, MD, Frederico Nunes, MD, Andre Aubert, MD, PhD, and Mohammed Bendabdallah, not M.D., Emmanuel Cluis, Anesthesia Nurse, Eric Wiel, MD, PhD, and Gilles Lebuffe, MD, PhD LILLE UNIVERSITY HOSPITAL, BAILLEUL, FRA; ANESTHESIOLOGY AND CRITICAL CARE, LILLE UNIVERSITY HOSPITAL, LILLE, FRA and LABORATORY OF EXPERIMENTAL CARDIOLOGY, UNIVERSITY HOSPITAL GASTHUISBERG, LEUVEN, BEL.

INTRODUCTION:The Mars500 project was conceived to gather knowledge about the psychological and physiological effects of living in an enclosed environment during 520 d as would be required for a real mission to Mars. Our objective was to investigate the circadian profile of heart rate variability (HRV) in the context of the Mars500 study.METHODS:Before, during, and after confinement, 24-h EKG records were obtained from the six crewmembers who participated in the mission. Autonomic activity was evaluated through time and frequency domain indexes of HRV analysis. Circadian rhythmicity was assessed both by averaging hourly HRV along wake and sleep scheduled periods and by fitting a 24-h harmonic to the hourly means.RESULTS:During confinement, wake HRV showed (mean +/- SE) a progressive increase in mean RR interval (from 778 +/- 24 ms to 916 +/- 42 ms), and in the amplitude (values are wavelet power coefficients) of very low (from 13.3 +/- 0.3 to 14.1 +/- 0.2) and high (from 7.8 +/- 0.4 to 8.3 +/- 0.3) frequency components. During sleep, the relative amplitude of the high frequency component of HRV decreased (from 11.8 +/- 1.6 to 9.4 +/- 1.8 normalized units). Overall, sleep-wake differences of HRV showed a progressive decrease of the relative amplitude of the high frequency component. Also, circadian HRV rhythms were dampened during confinement.DISCUSSION:Data revealed diminished amplitude of the rest-activity pattern of the autonomic nervous system parasympathetic function. Reduced daylight exposure and mood changes could account for this observation.