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      Tolerability of daily intermittent or continuous short-arm centrifugation during 60-day 6 o head down bed rest (AGBRESA study)

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          Abstract

          Artificial gravity through short-arm centrifugation has potential as a multi-system countermeasure for deconditioning and cranial fluid shifts that may underlie ocular issues in microgravity. However, the optimal short-arm centrifugation protocol that is effective whilst remaining tolerable has yet to be determined. Given that exposure to centrifugation is associated with presyncope and syncope and in addition motion sickness an intermittent protocol has been suggested to be more tolerable. Therefore, we assessed cardiovascular loading and subjective tolerability of daily short arm centrifugation with either an intermittent or a continuous protocol during long-term head-down bed rest as model for microgravity exposure in a mixed sex cohort. During the Artificial Gravity Bed Rest with European Space Agency (AGBRESA) 60 day 6° head down tilt bed rest study we compared the tolerability of daily +1 Gz exposure at the center of mass centrifugation, either performed continuously for 30 minutes, or intermittedly (6 x 5 minutes). Heart rate and blood pressure were assessed daily during centrifugation along with post motion sickness scoring and rate of perceived exertion. During bed rest, 16 subjects (6 women, 10 men), underwent 960 centrifuge runs in total. Ten centrifuge runs had to be terminated prematurely, 8 continuous runs and 2 intermittent runs, mostly due to pre-syncopal symptoms and not motion sickness. All subjects were, however, able to resume centrifuge training on subsequent days. We conclude that both continuous and intermittent short-arm centrifugation protocols providing artificial gravity equivalent to +1 Gz at the center of mass is tolerable in terms of cardiovascular loading and motion sickness during long-term head down tilt bed rest. However, intermittent centrifugation appears marginally better tolerated, albeit differences appear minor.

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          Long-duration bed rest as an analog to microgravity.

          Long-duration bed rest is widely employed to simulate the effects of microgravity on various physiological systems, especially for studies of bone, muscle, and the cardiovascular system. This microgravity analog is also extensively used to develop and test countermeasures to microgravity-altered adaptations to Earth gravity. Initial investigations of bone loss used horizontal bed rest with the view that this model represented the closest approximation to inactivity and minimization of hydrostatic effects, but all Earth-based analogs must contend with the constant force of gravity by adjustment of the G vector. Later concerns about the lack of similarity between headward fluid shifts in space and those with horizontal bed rest encouraged the use of 6 degree head-down tilt (HDT) bed rest as pioneered by Russian investigators. Headward fluid shifts in space may redistribute bone from the legs to the head. At present, HDT bed rest with normal volunteers is the most common analog for microgravity simulation and to test countermeasures for bone loss, muscle and cardiac atrophy, orthostatic intolerance, and reduced muscle strength/exercise capacity. Also, current physiologic countermeasures are focused on long-duration missions such as Mars, so in this review we emphasize HDT bed rest studies with durations of 30 days and longer. However, recent results suggest that the HDT bed rest analog is less representative as an analog for other important physiological problems of long-duration space flight such as fluid shifts, spinal dysfunction and radiation hazards.
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            Effects of Spaceflight on Astronaut Brain Structure as Indicated on MRI

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              Orthostatic intolerance after spaceflight.

              Orthostatic intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three space shuttle missions of 9-14 days. After spaceflight, 9 of the 14 (64%) crew members could not complete a 10-min stand test that all completed preflight. Pre- and postflight supine hemodynamics were similar in both groups except for slightly higher systolic and mean arterial pressures preflight in the finishers [15 +/- 3.7 and 8 +/- 1.2 (SE) mmHg, respectively; P < 0.05]. Postflight, finishers and nonfinishers had equally large postural reductions in stroke volume (-47 +/- 3.7 and -48 +/- 3.3 ml, respectively) and increases in heart rate (35 +/- 6.6 and 51 +/- 5.2 beats/min, respectively). Cardiac output during standing was also similar (3.6 +/- 0.4 and 4.1 +/- 0.3 l/min, respectively). However, the finishers had a greater postflight vasoconstrictor response with higher total peripheral resistance during standing (22.3 +/- 1.2 units preflight and 29.4 +/- 2.3 units postflight) than did the nonfinishers (20.1 +/- 1.1 units preflight and 19.9 +/- 1.4 units postflight). We conclude that 1) the primary systemic hemodynamic event, i.e., the postural decrease in stroke volume, was similar in finishers and nonfinishers and 2) the heart rate response and cardiac output during standing were not significantly different, but 3) the postural vasoconstrictor response was significantly greater among the finishers (P < 0.01).
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Investigation
                Role: Supervision
                Role: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 September 2020
                2020
                : 15
                : 9
                : e0239228
                Affiliations
                [1 ] Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany
                [2 ] Space Medicine Team, European Astronaut Centre, European Space Agency, Cologne, Germany
                [3 ] KBRwyle GmbH, Cologne, Germany
                [4 ] King’s College London, London, United Kingdom
                [5 ] Institutes of Sports Medicine, Hannover Medical School, Hannover, Germany
                [6 ] Chair of Aerospace Medicine, University of Cologne, Cologne, Germany
                Tokyo Joshi Ika Daigaku Toyo Igaku Kenkyujo Clinic, JAPAN
                Author notes

                Competing Interests: The authors declare no competing interests as KBRwyle GmbH had no role in the study design and thus this does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-5572-1177
                Article
                PONE-D-20-13193
                10.1371/journal.pone.0239228
                7500599
                32946482
                babace48-50d7-48ec-997d-75a2e2061117
                © 2020 Frett et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 May 2020
                : 1 September 2020
                Page count
                Figures: 4, Tables: 2, Pages: 11
                Funding
                The “Artificial Bed Rest study with European Space Agency” (ABRESA) study was financed by NASA and ESA. Our experiments were included into the study conduction and financed by the DLR Institute of Aerospace Medicine. KBRwyle GmbH provided support in the form of salaries only for author D.G, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Research and Analysis Methods
                Separation Processes
                Centrifugation
                Engineering and Technology
                Equipment
                Laboratory Equipment
                Centrifuges
                Physical Sciences
                Physics
                Gravitation
                Artificial Gravity
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Cardiology
                Heart Rate
                Physical Sciences
                Physics
                Classical Mechanics
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Physical Sciences
                Physics
                Classical Mechanics
                Motion
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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                Uncategorized

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