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Aims Reduced physical activity increases the risk of heart failure; however, non‐invasive methodologies detecting subclinical changes in myocardial function are not available. We hypothesized that myocardial, left ventricular, systolic strain measurements could capture subtle abnormalities in myocardial function secondary to physical inactivity. Methods and results In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (eight women) were submitted to 60 day strict −6° head‐down‐tilt bed rest. Participants were assigned to three groups of eight subjects: a control group, continuous artificial gravity training on a short‐arm centrifuge (30 min/day), or intermittent centrifugation (6 × 5 min/day). We assessed cardiac morphology, function, strain, and haemodynamics by cardiac magnetic resonance imaging (MRI) and echocardiography. We observed no differences between groups and, therefore, conducted a pooled analysis. Consistent with deconditioning, resting heart rate (∆8.3 ± 6.3 b.p.m., P

Prolonged exposure to microgravity during spaceflights leads to severe deterioration in the physical performance of astronauts. To understand the effectiveness of existing in‐flight daily countermeasures and to plan exercise onboard the International Space Station, we compared supine treadmill running to traditional upright treadmill running on earth. Specifically, we assessed the cardiorespiratory responses to conventional upright running to the responses to supine treadmill running under 0.3 g, 0.6 g, and 1 g of body weight in younger (20–30 years, n = 14, 8 females) and older healthy adults (50–60 years, n = 12, 6 females). Maximal cardiorespiratory capacity was additionally evaluated by performing an incremental running protocol on each treadmill. Maximum speed was greater for 0.3 g and 0.6 g in supine than for upright running (18.5 km/h (1.1) and 15.9 (3.1) vs 13.2 (2.4) p, To better understand astronauts’ physical performance in reduced gravity, we studied heart rate and oxygen uptake responses in supine treadmill running under simulated microgravity conditions. The maximum achievable metabolic rate (V˙O2max) was lower by 20% in supine running, as compared to upright running, and maximum heart rate (HRmax) was likewise reduced. Oxygen uptake (V˙O2) values were well predicted by the level of gravity reduction and running speed. This is of relevance for astronaut health, as low metabolic rate during exercise compromises the expected health benefits for space travelers.

Although acute hypoxia is of utmost pathophysiologic relevance in health and disease, studies on its effects on both the macro- and microcirculation are scarce. Herein, we provide a comprehensive analysis of the effects of acute normobaric hypoxia on human macro- and microcirculation. 20 healthy participants were enrolled in this study. Hypoxia was induced in a normobaric hypoxia chamber by decreasing the partial pressure of oxygen in inhaled air stepwisely (pO₂; 21.25 kPa (0 k), 16.42 kPa (2 k), 12.63 kPa (4 k) and 9.64 kPa (6 k)). Macrocirculatory effects were assessed by cardiac output measurements, microcirculatory changes were investigated by sidestream dark-field imaging in the sublingual capillary bed and videocapillaroscopy at the nailfold. Exposure to hypoxia resulted in a decrease of systemic vascular resistance (p

In addition to tissues such as liver, the plasma membrane sodium-dependent citrate transporter, NaCT (SLC13A5), is highly expressed in brain neurons, but its function is not understood. Loss-of-function mutations in the human SLC13A5 gene have been associated with severe neonatal encephalopathy and pharmacoresistant seizures. The molecular mechanisms of these neurological alterations are not clear. We performed a detailed examination of a Slc13a5 deletion mouse model including video-EEG monitoring, behavioral tests, and electrophysiologic, proteomic, and metabolomic analyses of brain and cerebrospinal fluid. The experiments revealed an increased propensity for epileptic seizures, proepileptogenic neuronal excitability changes in the hippocampus, and significant citrate alterations in the CSF and brain tissue of Slc13a5 deficient mice, which may underlie the neurological abnormalities. These data demonstrate that SLC13A5 is involved in brain citrate regulation and suggest that abnormalities in this regulation can induce seizures. The present study is the first to (i) establish the Slc13a5-knockout mouse model as a helpful tool to study the neuronal functions of NaCT and characterize the molecular mechanisms by which functional deficiency of this citrate transporter causes epilepsy and impairs neuronal function; (ii) evaluate all hypotheses that have previously been suggested on theoretical grounds to explain the neurological phenotype of SLC13A5 mutations; and (iii) indicate that alterations in brain citrate levels result in neuronal network excitability and increased seizure propensity.

Im Rahmen der Weiterentwicklung der bemannten Raumfahrt hat sich in den letzten Jahren gezeigt, dass neben anderen Organsystemen auch das Auge bei längerfristigen Aufenthalten in der Schwerelosigkeit erhebliche Veränderungen aufweist. Unter dem Begriff „Space Flight-Associated-Neuro-Ocular-Syndrom“ (SANS) werden okuläre Veränderungen zusammengefasst, die man bei Astronauten nach längerfristigen Aufenthalten im Weltall auf der internationalen Raumstation ISS, festgestellt hat. Die Veränderungen des SANS umfassen teilweise nicht vollständig reversible Pathologie wie uni- und bilaterale Papillenödeme (rechts häufiger als links), Distensionen der Optikusscheiden, einen hyperopen Shift, Bulbusabflachungen, Aderhautfalten und Cotton-wool-Herde [1]. Da diese Veränderungen gerade bei längeren Raumflügen z. B. zum Mars oder möglicherweise auch bei längerfristigen Aufenthalten in reduzierter Schwerkraft auf dem Mond zu relevanten Beeinträchtigungen der Sehfähigkeit der Astronauten führen könnten, besteht hier ein erhebliches Interesse, die Pathophysiologie dieser „Space-Eye-Disease“ zu verstehen und präventive bzw. therapeutische Möglichkeiten zu entwickeln. Sonst könnte SANS bei längeren Raumflügen nicht nur die Augengesundheit der Astronautinnen und Astronauten beeinträchtigen, sondern den Erfolg und die Sicherheit der ganzen Mission gefährden.

Roman M. Baevsky, a dedicated scientist, compassionate physician, beloved mentor, and dear friend left us on May 31, 2020 at the age of 91 years. He had served as chief researcher at the scientific center of the Russian Federation—Institute of Biomedical Problems of the Russian Academy of Sciences (IBMP). Throughout his career, his work was focused on autonomic cardiovascular control mechanisms and how they are challenged in extreme environments, particularly during space travel. Moreover, he developed the concept that non-invasive cardiovascular autonomic testing could identify individuals at increased risk before symptoms occurred to guide preventive measures.

Cardiovascular regulation is integral to life. Animal studies have identified both neural and endocrine pathways, by which the central nervous system adjusts cardiac output and peripheral vascular resistance to changing physiological demands. The outflow of these pathways is coordinated by various central nervous regions based on afferent information from baroreceptors, chemoreceptors, nociceptors, and circulating hormones, and is modulated by physiologic and behavioural state. In humans, however, knowledge on central cardiovascular regulation below the cortical level is scarce. Here, we show using functional MRI (fMRI) that at least three hypothalamic subsystems are involved in cardiovascular regulation in humans. The rhythmic behaviour of these systems corresponds to high and low frequency oscillations typically seen in blood pressure and heart rate variability., eLife digest Stand up too fast and you know what happens next. You will feel faint as the blood rushes away from your head. Gravity pulls the blood into your legs, and your blood pressure drops. To correct this imbalance, the brain sends nerve impulses telling the heart to beat faster and the outer blood vessels to tighten. This is the autonomic nervous system at work. It is how the brain adjusts cardiac output, and quietly controls other internal organs in the body. It involves two key regions of the brain, the hypothalamus and the brainstem, and stimulates smooth muscles and glands around the body. The cardiovascular system also responds to the demands of exercise, with the heart supplying fresh blood laden with oxygen and the blood clearing out waste materials as it flows around the body. Perhaps surprisingly, blood pressure and heart rate fluctuate even at rest. The heart beats faster when breathing in and slower when breathing out. People’s blood pressure, the force that keeps blood moving through arteries, also oscillates in so-called Mayer waves that last about 10 seconds. Much of the current understanding of the inner workings of the cardiovascular system – and how it is regulated by the brain – stems from animal experiments. This is because few attempts have been made to simultaneously measure how a person’s brain and cardiovascular system work with enough detail to see how brain waves and cardiac oscillations might interact. To achieve this, Manuel et al. have now measured the brain activity, pulse and blood pressure of twenty-two healthy people while they were lying down in an MRI machine. This revealed that three distinct parts of the hypothalamus regulate cardiovascular output in humans. These ‘subsystems’ communicate with each other and with the lower brainstem, which sits beneath the hypothalamus. Manuel et al. also observed that the rhythmic activity of these subsystems runs in sync with oscillations typically seen in heart rate and blood pressure. With this work, Manuel et al. have shown that it is feasible to measure different systems of cardiovascular control in humans. In time, with further experiments using this new approach, the understanding of chronic high blood pressure and heart failure may improve.

Hintergrund Augenveränderungen bei Astronautinnen und Astronauten, insbesondere das „spaceflight associated neuro-ocular syndrome“ (SANS), sind eine medizinische Herausforderung, für die es bisher noch keine geeignete Präventionsmaßnahme gibt. Bei längeren Weltraummissionen z. B. zu Mond und Mars könnten SANS und die strahlenbedingte Katarakt die Gesundheit und Leistungsfähigkeit der Crews und den Erfolg der Missionen gefährden. Für mechanistische Studien und Entwicklung präventiver Verfahren sind geeignete terrestrische Modelle erforderlich. Ziele der Arbeit Es soll eine Übersicht über den aktuellsten Forschungsstand und künftige Bestrebungen in der Weltraummedizin gegeben werden. Material und Methoden Es erfolgt eine Analyse der relevanten Veröffentlichungen anhand von PubMed. Ergebnisse In den Bettruhestudien des Instituts für Luft- und Raumfahrtmedizin des DLR (Deutsches Zentrum für Luft- und Raumfahrt) konnte gezeigt werden, dass strikte Bettruhe in −6° Kopftieflage Veränderungen wie bei SANS auf der Erde reproduzieren kann. Das Modell inklusive der Erzeugung von Papillenödemen wird eingesetzt, um die Wirkung künstlicher Schwerkraft mittels Kurzarmzentrifugation als präventive Maßnahme zu untersuchen. Die einzigartige Forschungseinrichtung :envihab bietet die Möglichkeit, während der Bettruhestudien auch die Umgebungsbedingungen wie auf der Internationalen Raumstation zu simulieren. Schlussfolgerung Künftige Bettruhestudien in Kopftieflage sollen dazu dienen, Verfahren für die Prävention von SANS systematisch zu prüfen. Dies wäre unter realen Weltraumbedingungen schwer zu realisieren. Durch eine enge Kooperation von Weltraummedizin und terrestrischer Ophthalmologie soll diese Forschung auch Patienten auf der Erde zugutekommen.

Hintergrund Der menschliche Augeninnendruck (intraokularer Druck [IOD]) ist abhängig von der Lage des Kopfes im Verhältnis zum Körper im Raum. Physiologisch steigt der IOD bei liegender Position im Vergleich zur aufrechten Körperhaltung an. Auch in der Schwerelosigkeit im Weltall scheint es zu einer Erhöhung des Augeninnendrucks zu kommen, begleitet von anderen ophthalmologischen Symptomen, die unter dem Krankheitsbegriff „Spaceflight Associated Neuro-Ocular Syndrome“ (SANS) zusammengefasst werden. Um die Auswirkungen des Einsatzes in der Schwerelosigkeit auf den menschlichen Körper zu untersuchen, werden sog. Bed-Rest-Studien durchgeführt. Hier besteht also eine Schnittmenge zwischen der Erforschung des SANS und der Glaukomerkrankung. Ein erhöhter Augeninnendruck ist weiterhin der wichtigste durch Therapie zu beeinflussende Risikofaktor für eine Glaukomentstehung und -progression. Der Einfluss von lageabhängiger IOD-Schwankungen auf die Glaukomerkrankung ist weiterhin nicht ausreichend verstanden. Methoden Es erfolgten die Durchführung einer Literaturrecherche via PubMed zum Thema „lageabhängige Augeninnendruckschwankungen“, eine Analyse und Einordnung der veröffentlichten Studienergebnisse sowie eine zusammenfassende Bewertung dieser. Ergebnisse Der Augeninnendruckanstieg beim Wechsel von sitzender zu liegender Körperposition ist bei Glaukompatienten mit bis zu 8,6 mm Hg stärker als bei gesunden Probanden mit bis zu 5 mm Hg. In kleinen Pilotstudien konnte eine Kopfhochlagerung um 30 % bei einem Teil der Glaukompatienten bzw. gesunden Probanden den IOD-Anstieg im Liegen abmildern. Ein erniedrigter Kompartimentdruck im Subarachnoidalraum wurde mit der Glaukomerkrankung assoziiert und kann einen Risikofaktor für die Glaukomentstehung darstellen. Nicht nur die Höhe des Augeninnendrucks, sondern auch IOD-Schwankungen wurden mit dem Risiko einer höheren Progressionswahrscheinlichkeit assoziiert. Schlussfolgerung Die klinische Bedeutung von nächtlichen IOD-Spitzen im Liegen für die Glaukomerkrankung ist weiterhin nicht ausreichend verstanden Neue Verfahren zur kontinuierlichen Augeninnendruckmessung bieten vielversprechende Möglichkeiten zur weiteren Erforschung der Bedeutung von lageabhängigen IOD-Schwankungen.

Hintergrund Mehr denn je rückt die Erforschung der Veränderungen am Auge, die durch den Aufenthalt im All verursacht werden, ins Zentrum des Interesses der internationalen und nationalen Weltraumagenturen NASA (National Aeronautics and Space Administration), ESA (European Space Agency) und DLR (Deutsches Zentrum für Luft- und Raumfahrt). Neben weltraumstrahlungbedingten Katarakten können erhebliche Augenveränderungen, zusammengefasst unter dem „space flight-associated neuro-ocular syndrome“ (SANS) auftreten. Ziele der Arbeit Diese Übersicht soll den aktuellen Forschungsstand und künftige Bestrebungen auf dem Gebiet der Erforschung der Augenveränderungen bei SANS wiedergeben und die Relevanz für die terrestrische ophthalmologische Forschung aufzeigen. Material und Methoden Es erfolgt eine Analyse der bestehenden Publikationen zu dem Thema in PubMed sowie von Berichten bezüglich des Risikos von SANS, veröffentlicht von der NASA der USA. Ergebnisse Die Ursachen für die Entstehung der Augenveränderungen im All sind nicht geklärt. Faktoren wie die Erhöhung des intrakraniellen Drucks, Flüssigkeitsverschiebungen, Hyperkapnie und genetische Einflüsse sind Gegenstand intensiver Forschungsbemühungen. Ein terrestrisches Modell zur Induktion des Papillenödems konnte etabliert werden (Bettruhestudien mit −6° Kopftieflagerung als Weltraumanalogon). Gegenmaßnahmen zur Entwicklung der Augenveränderungen, wie beispielsweise intermittierend künstliche Schwerkraft, sind Gegenstand der aktuellen Studien. Schlussfolgerung Die Erforschung von SANS im Rahmen von Bettruhestudien wird in Zukunft sowohl für die Weltraumforschung als auch für die terrestrische Forschung weitere wichtige Erkenntnisse liefern. Klinische Forschungsprojekte können aus der Weltraumforschung abgeleitet werden.

Baroreceptors are pressure sensors on specialized neurons that specifically detect stretch within arterial walls, which occurs when BP increases. When baroreceptors are stretched, they transmit afferent (sensory) signals to the nucleus tractus solitarii in the medulla. These signals inhibit

Introduction Baroreflexes and peripheral chemoreflexes control efferent autonomic activity making these reflexes treatment targets for arterial hypertension. The literature on their interaction is controversial, with suggestions that their individual and collective influence on blood pressure and heart rate regulation is variable. Therefore, we applied a study design that allows the elucidation of individual baroreflex–chemoreflex interactions. Methods We studied nine healthy young men who breathed either normal air (normoxia) or an air–nitrogen–carbon dioxide mixture with decreased oxygen content (hypoxia) for 90 min, with randomization to condition, followed by a 30-min recovery period and then exposure to the other condition for 90 min. Multiple intravenous phenylephrine bolus doses were applied per condition to determine phenylephrine pressor sensitivity as an estimate of baroreflex blood pressure buffering and cardiovagal baroreflex sensitivity (BRS). Results Hypoxia reduced arterial oxygen saturation from 98.1 ± 0.4 to 81.0 ± 0.4% (p p p = 0.182). Of the nine subjects, six had significantly lower BRS in hypoxia (p p p p = 0.878). Conclusion We applied an approach to assess individual baroreflex–chemoreflex interactions in human subjects. A subgroup exhibited significant impairments in baroreflex blood pressure buffering and BRS with peripheral chemoreflex activation. The methodology may have utility in elucidating individual pathophysiology and in targeting treatments modulating baroreflex or chemoreflex function.

Background Hypergravity may promote human hemostasis thereby increasing thrombotic risk. Future touristic suborbital spaceflight will expose older individuals with chronic medical conditions, who are at much higher thromboembolic risk compared with professional astronauts, to hypergravity. Therefore, we tested the impact of hypergravity on hemostasis in healthy volunteers undergoing centrifugation. Methods and Results We studied 20 healthy seated men before and after 15 minutes under 3 Gz hypergravity on a long-arm centrifuge. We obtained blood samples for hemostasis testing before, immediately after, and 30 minutes after centrifugation. Tests included viscoelastic thromboelastometry, platelet impedance aggregometry, endothelial activation markers, blood rheology testing, microparticle analyses, and clotting factor analysis. Exposure to hypergravity reduced plasma volume by 12.5% (P=0.002) and increased the red blood cell aggregation index (P

The solute carrier (SLC) superfamily comprises more than 400 transport proteins mediating the influx and efflux of substances such as ions, nucleotides, and sugars across biological membranes. Over 80 SLC transporters have been linked to human diseases, including obesity and type 2 diabetes (T2D). This observation highlights the importance of SLCs for human (patho)physiology. Yet, only a small number of SLC proteins are validated drug targets. The most recent drug class approved for the treatment of T2D targets sodium-glucose cotransporter 2, product of the SLC5A2 gene. There is great interest in identifying other SLC transporters as potential targets for the treatment of metabolic diseases. Finding better treatments will prove essential in future years, given the enormous personal and socioeconomic burden posed by more than 500 million patients with T2D by 2040 worldwide. In this review, we summarize the evidence for SLC transporters as target structures in metabolic disease. To this end, we identified SLC13A5/sodium-coupled citrate transporter, and recent proof-of-concept studies confirm its therapeutic potential in T2D and nonalcoholic fatty liver disease. Further SLC transporters were linked in multiple genome-wide association studies to T2D or related metabolic disorders. In addition to presenting better-characterized potential therapeutic targets, we discuss the likely unnoticed link between other SLC transporters and metabolic disease. Recognition of their potential may promote research on these proteins for future medical management of human metabolic diseases such as obesity, fatty liver disease, and T2D. SIGNIFICANCE STATEMENT: Given the fact that the prevalence of human metabolic diseases such as obesity and type 2 diabetes has dramatically risen, pharmacological intervention will be a key future approach to managing their burden and reducing mortality. In this review, we present the evidence for solute carrier (SLC) genes associated with human metabolic diseases and discuss the potential of SLC transporters as therapeutic target structures.

The cortical structure of human fibula varies widely throughout the bone suggesting a more selective adaptation to different mechanical environments with respect to the adjacent tibia. To test this hypothesis, serial-pQCT scans of the dominant fibulae and tibiae of 15/15 men/women chronically trained in long-distance running were compared with those of 15/15 untrained controls. When compared to controls, the fibulae of trained individuals had similar (distally) or lower (proximally) cortical area, similar moments of inertia (MI) for anterior-posterior bending (xMI) and lower for lateral bending (yMI) with a lower “shape-index” (yMI/xMI ratio) throughout, and higher resistance to buckling distally. These group differences were more evident in men and independent of group differences in bone mass. These results contrast with those observed in the tibia, where, as expected, structural indicators of bone strength were greater in trained than untrained individuals. Proximally, the larger lateral flexibility of runners' fibulae could improve the ability to store energy, and thereby contribute to fast-running optimization. Distally, the greater lateral fibular flexibility could reduce bending strength. The latter appears to have been compensated by a higher buckling strength. Assuming that these differences could be ascribed to training effects, this suggests that usage-derived strains in some bones may modify their relative structural resistance to different kinds of deformation in different regions, not only regarding strength, but also concerning other physiological roles of the skeleton. Fil: Luscher, Sergio Hugo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Nocciolino, Laura Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Pilot, Nicolas Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Pisani, Leonardo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Ireland, Alex. Manchester Metropolitan University; Reino Unido Fil: Rittweger, Jörn. Centro Aero Espacial Aleman; Alemania. Universitat zu Köln; Alemania Fil: Ferretti, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Cointry, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina Fil: Capozza, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Estudios de Metabolismo Fosfocálcico; Argentina

Aims Prolonged immobilization generates cardiac deconditioning, a risk factor for cardiovascular disease, and efficient countermeasures (CM) are needed to prevent it. Our aim was to assess by Cine-MRI the effects of long-term strict head-down (−6 degrees) bed-rest (BR) deconditioning, and the effectiveness of high-intensity jump training CM, on left ventricular (LV) function and mass. Methods 23 male participants (29±6 years, 181±6 cm, 77±7 kg) were enrolled. The experiment was conducted at: envihab (Koln, DLR, Germany) as part of the European Space Agency BR studies. Volunteers were randomly allocated to the jump training group (JUMP, n=12) or the control group (CTRL, n=11). A typical training session consisted of 4x10 countermovement jumps and 2x10 hops in a sledge jump system, with 5–6 sessions per week. Steady-state free precession cine-MRI images were obtained (25 frames/cardiac cycle, 8mm thickness, no gap, no overlap) as stack of short-axis images covering the whole LV from base to apex, before (PRE) and after 58-days (HDT58) of BR. Endocardial and epicardial semi-automated contouring was performed using custom software. Results In CTRL group, at HDT58 a reduction in LV mass (9%), end-diastolic (21%), end-systolic (8%) and stroke volume (23%) were observed, while ejection fraction did not change. In JUMP group, the reduction in LV end-diastolic volume was only by 9%, followed by a decrease in end-systolic (10%) and stroke volume (10%), with a preservation of LV mass. In both groups, ejection fraction did not change.

We hypothesized that sympathetic baroreflex mediated uncoupling between neural sympathetic discharge pattern and arterial pressure (AP) fluctuations at 0.1 Hz during baroreceptor unloading might promote orthostatic pre-syncope. Ten volunteers (32 &plusmn, 6 years) underwent electrocardiogram, beat-to-beat AP, respiratory activity and muscle sympathetic nerve activity (MSNA) recordings while supine (REST) and during 80&deg, head-up tilt (HUT) followed by &minus, 10 mmHg stepwise increase of lower body negative pressure until pre-syncope. Cardiac and sympathetic baroreflex sensitivity were quantified. Spectrum analysis of systolic and diastolic AP (SAP and DAP) and calibrated MSNA (cMSNA) variability assessed the low frequency fluctuations (LF, ~0.1 Hz) of SAP, DAP and cMSNA variability. The squared coherence function (K2) quantified the coupling between cMSNA and DAP in the LF band. Analyses were performed while supine, during asymptomatic HUT (T1) and at pre-syncope onset (T2). During T2 we found that: (1) sympathetic baroreceptor modulation was virtually abolished compared to T1, (2) a progressive decrease in AP was accompanied by a persistent but chaotic sympathetic firing, (3) coupling between cMSNA and AP series at 0.1 Hz was reduced compared to T1. A negligible sympathetic baroreceptor modulation during pre-syncope might disrupt sympathetic discharge pattern impairing the capability of vessels to constrict and promote pre-syncope.

Orthostatic intolerance commonly occurs after prolonged bed rest, thus increasing the risk of syncope and falls. Baroreflex-mediated adjustments of heart rate and sympathetic vasomotor activity (muscle sympathetic nerve activity – MSNA) are crucial for orthostatic tolerance. We hypothesized that prolonged bed rest deconditioning alters overall baroreceptor functioning, thereby reducing orthostatic tolerance in healthy volunteers. As part of the European Space Agency Medium-term Bed Rest protocol, 10 volunteers were studied before and after 21 days of −6° head down bed rest (HDBR). In both conditions, subjects underwent ECG, beat-by-beat blood pressure, respiratory activity, and MSNA recordings while supine (REST) and during a 15-min 80° head-up tilt (TILT) followed by a 3-min −10 mmHg stepwise increase of lower body negative pressure to pre-syncope. Cardiac baroreflex sensitivity (cBRS) was obtained in the time (sequence method) and frequency domain (spectrum and cross-spectrum analyses of RR interval and systolic arterial pressure – SAP, variability). Baroreceptor modulation of sympathetic discharge activity to the vessels (sBRS) was estimated by the slope of the regression line between the percentage of MSNA burst occurrence and diastolic arterial pressure. Orthostatic tolerance significantly decreased after HDBR (12 ± 0.6 min) compared to before (21 ± 0.6 min). While supine, heart rate, SAP, and cBRS were unchanged before and after HDBR, sBRS gain was slightly depressed after than before HDBR (sBRS: −6.0 ± 1.1 versus −2.9 ± 1.5 burst% × mmHg−1, respectively). During TILT, HR was higher after than before HDBR (116 ± 4 b/min versus 100 ± 4 b/min, respectively), SAP was unmodified in both conditions, and cBRS indexes were lower after HDBR (α index: 3.4 ± 0.7 ms/mmHg; BRSSEQ 4.0 ± 1.0) than before (α index: 6.4 ± 1.0 ms/mmHg; BRSSEQ 6.8 ± 1.2). sBRS gain was significantly more depressed after HDBR than before (sBRS: −2.3 ± 0.7 versus −4.4 ± 0.4 burst% × mmHg−1, respectively). Our findings suggest that baroreflex-mediated adjustments in heart rate and MSNA are impaired after prolonged bed rest. The mechanism likely contributes to the decrease in orthostatic tolerance.

Purpose: The environmental conditions in space, particularly exposure to cosmic radiation, coupled with decreased mobility, altered glucose metabolism, and hemodynamic changes may promote cardiovascular disease Therefore, we assessed early vascular aging markers and hemodynamics using a novel oscillometric blood pressure device. Methodology: In eight cosmonauts (46.5 ​± ​5.3 ​yrs, 77.6 ​± ​8.2 ​kg, 176 ​± ​6.2 ​cm, 7 men/1woman), we determined heart rate, peripheral blood pressure, central blood pressure, and pulse wave velocity in the supine position using an oscillometric brachial device coupled with transfer function analysis. We obtained measurements at baseline (65–90 days before flight) and four days (R+4) and eight days (R+8) after return from six months mission onboard the International Space Station. Results: Compared to baseline, heart rate increased significantly on R+4 (58.6 ​± ​6.4 vs. 70.3 ​± ​5.2 bpm) but did not differ on R+8. Central systolic blood pressure increased from 112.5 ​± ​13.5 on baseline to 125.6 ​± ​18.5 on R+4 and 121.6 ​± ​9.5 ​mmHg, albeit showing no statistical significance compared to baseline (p ​= ​0.243/0.295). Peripheral diastolic and systolic as well as central diastolic blood pressure measurements followed this trend. Pulse wave velocity increased non-significantly from baseline (6.7 ​± ​0.8 ​m/s) to R+4 (7.2 ​± ​0.8 ​m/s, p ​= ​0.499) and stayed elevated on R+8 (7.1 ​± ​0.5 ​m/s, p ​= ​0.614). Conclusion: The important finding of our study is that six months in a near-earth orbit do not lead to clinically significant changes in early vascular ageing biomarkers. However, these findings cannot be extrapolated to the conditions encountered in deep space. Non-invasive testing of vascular biomarkers may have utility in detecting vascular risks during space travel at an early stage.

Recent studies are elucidating the interrelation between sleep, cranial perfusion, and cerebrospinal fluid (CSF) circulation. Head down tilt (HDT) as a simulation of microgravity reduces cranial perfusion. Therefore, our aim was to assess whether HDT is affecting sleep (clinicaltrials.gov; identifier NCT 02976168). 11 male subjects were recruited for a cross-over designed study. Each subject participated in two campaigns each comprising 3 days and 2 nights. Intervention started on the second campaign day and consisted of maintenance of horizontal position or −12° HDT for 21 h. Ultrasound measurements were performed before, at the beginning and the end of intervention. Polysomnographic measurements were assessed in the second night which was either spent in horizontal posture or at −12° HDT. Endpoints were sleep efficiency, sleep onset latency, number of sleep state changes and arousals, percentages of N3, REM, light sleep stages and subjective sleep parameters. N3 and REM sleep reduced by 25.6 and 19.1 min, respectively (P = 0.002, g = -0.898; P = 0.035, g = -0.634) during −12° HDT. Light sleep (N1/2) increased by 33.0 min at −12° HDT (P = 0.002, g = 1.078). On a scale from 1 to 9 subjective sleep quality deteriorated by 1.3 points during −12° HDT (P = 0.047, g = -0.968). Ultrasonic measurement of the venous system showed a significant increase of the minimum (P = 0.009, P < 0.001) and maximum (P = 0.004, P = 0.002) cross-sectional area of the internal jugular vein at −12° HDT. The minimum cross-sectional area of the external jugular vein differed significantly between conditions over time (P = 0.001) whereas frontal skin tissue thickness was not significantly different between conditions (P = 0.077, P = 0.811). Data suggests venous congestion at −12° HDT. Since subjects felt comfortable with lying in −12° HDT under our experimental conditions, this posture only moderately deteriorates sleep. Obviously, the human body can almost compensate the several fold effects of gravity in HDT posture like an affected CSF circulation, airway obstruction, unusual patterns of propioception and effects on the cardiovascular system.

Cardiovascular risk rapidly increased following exposure to air pollution. Changes in human autonomic regulation have been implicated based on epidemiological associations between exposure estimates and indirect autonomic nervous system measurements. We conducted a mechanistic study to test the hypothesis that, in healthy older individuals, well-defined experimental exposure to ultrafine carbon particles (UFP) increases sympathetic nervous system activity and more so with added ozone (O3). Eighteen participants (age >50 years, 6 women) were exposed to filtered air (Air), UFP, and UFP + O3 combination for 3 hours during intermittent bicycle ergometer training in a randomized, crossover, double-blind fashion. Two hours following exposure, respiration, electrocardiogram, blood pressure, and muscle sympathetic nerve activity (MSNA) were recorded at supine rest, during deep breathing, and during a Valsalva manoeuvre. Catechols and inflammatory marker levels were measured in venous blood samples. Induced sputum was obtained 3.5 h after exposure. Combined exposure to UFP + O3 but not UFP alone, caused a significant increase in sputum neutrophils and circulating leucocytes. Norepinephrine was modestly increased while the ratio between plasma dihydroxyphenylglycol (DHPG) and norepinephrine levels, a marker for norepinephrine clearance, was reduced with UFP + O3. Resting MSNA was not different (47 ± 12 with Air, 47 ± 14 with UFP, and 45 ± 14 bursts/min with UFP + O3). Indices of parasympathetic heart rate control were unaffected by experimental air pollution. Our study suggests that combined exposure to modest UFP and O3 levels increases peripheral norepinephrine availability through decreased clearance rather than changes in central autonomic activity. Pulmonary inflammatory response may have perturbed pulmonary endothelial norepinephrine clearance.

Introduction: Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Yet, brainstem function is difficult to explore in living humans and is therefore mostly studied using animal models or postmortem human anatomy studies. We developed a methodology to identify brainstem nuclei involved in baroreflex cardiovascular control in humans by combining pharmacological baroreflex testing with functional magnetic resonance imaging. Materials and Methods: In 11 healthy men, we applied eight repeated intravenous phenylephrine bolus doses of 25 and 75 μg followed by a saline flush using a remote-controlled injector during multiband functional magnetic resonance imaging (fMRI) acquisition of the whole brain including the brainstem. Continuous finger arterial blood pressure, respiration, and electrocardiogram (ECG) were monitored. fMRI data were preprocessed with a brainstem-specific pipeline and analyzed with a general linear model (GLM) to identify brainstem nuclei involved in central integration of the baroreceptor input. Results: Phenylephrine elicited a pressor response followed by a baroreflex-mediated lengthening of the RR interval (25 μg: 197 ± 15 ms; 75 μg: 221 ± 33 ms). By combining fMRI responses during both phenylephrine doses, we identified significant signal changes in the nucleus tractus solitarii (t = 5.97), caudal ventrolateral medulla (t = 4.59), rostral ventrolateral medulla (t = 7.11), nucleus ambiguus (t = 5.6), nucleus raphe obscurus (t = 6.45), and several other brainstem nuclei [p < 0.0005 family-wise error (few)-corr.]. Conclusion: Pharmacological baroreflex testing during fMRI allows characterizing central baroreflex regulation at the level of the brainstem in humans. Baroreflex-mediated activation and deactivation patterns are consistent with previous investigations in animal models. The methodology has the potential to elucidate human physiology and mechanisms of autonomic cardiovascular disease.

Poster Abstract: The recent Medium-term Bed Rest Study - VaPER was conducted in 2017 as joint project between NASA and DLR in Cologne, Germany. The primary aim of this comprehensive study was to test influences of the novel paradigm for microgravity simulation combining - 6° head down tilt (HDT) with increased ambient CO2 (0.5%) on cerebral and ocular anatomy and physiology. The study focused on the Spaceflight Associated Neuro-ocular Syndrome (SANS, formerly the visual impairment and intracranial pressure, or VIIP syndrome). On the ISS, astronauts are exposed to microgravity and increased ambient CO2 (hypercapnia). Hypercapnia potently augments cerebral blood flow which may acutely increase intracranial blood volume and intracranial pressure. When added to the cephalad fluid shifts in space, hypercapnia may further raise intracranial pressure and hence SANS risk. HDT has stood the test of time as ground-based microgravity analogue for space medicine research. However, unlike in microgravity where all hydrostatic gradients are abolished, a gravitation vector is still present in HDT bed rest which may elicit different physiological responses. Indeed, -6° HDT studies have not reproduced cerebral or ophthalmic findings observed in astronauts affected by SANS. Possibly, -6° HDT alone may not create head-ward fluid shifts mimicking true microgravity conditions. Steeper HDT tilt angles are unrealistic for long-duration bed rest studies. On the other hand, all experimental bed rest studies thus far provided pillows. Consequently, we sought to establish whether the bed rest model for SANS-related research could be improved by mimicking hypercapnia on board the ISS and stricter controlled -6° HDT bed rest position. During the VaPER Study no pillows were permitted except for a thin pillow when subjects were lying on their sides. Subjects were camera-monitored 24 h per day and feedback on head position was provided during waking hours whenever needed. Test subjects showed an excellent adherence and maintained strict -6° HDT throughout the study. Adherence is of central importance for successful completion of bed rest studies. One prerequisite is careful screening before study inclusion with an emphasis on psychological aspects. The :envihab facility and the experienced staff at the DLR-Institute of Aerospace Medicine create an atmosphere of best possible well-being during confinement. Within the next NASA-ESA-DLR Longterm-Bedrest Study (ABGRESA-Study) planned in 2019 we will get more information to determine whether strict -6° HDT bed rest, hypercapnia, or both combined are required to model SANS-like findings.

Einleitung: Im Herbst 2017 wurde eine Bettruhestudie mit dem Titel “Medium-term Bed Rest Study - VIIP and Psychological :envihab Research Study (VaPER)” als gemeinsames Projekt der NASA und des DLR in Köln durchgeführt. Hauptziel dieser Studie war es unter Simulation von physiologischen Effekten der Schwerelosigkeit, in dem Fall 30-tägiger Bettruhe in -6°-Kopftieflage, Einflüsse auf Anatomie und Physiologie des Gehirns sowie des Auges zu untersuchen. Seit 2011 bekannt wurde, dass bei einzelnen Astronauten nach ihrer Rückkehr aus mehrmonatiger Mission auf der ISS Augenveränderungen festgestellt worden sind (1), das sogenannte SANS, das Spaceflight Associated Neuroocular Syndrome (früher VIIP-Syndrom), steht die Erforschung dieser Augenveränderung verstärkt im Fokus, so auch bei der VaPER-Studie. Die Raumfahrt-Medizin bedient sich zur Erforschung der Auswirkungen von Schwerlosigkeit auf den menschlichen Körper auf der Erde seit Jahrzehnten eines Modells für Mikrogravitations-Simulation, der Bettruhe in -6° Kopftieflage (Head-Down-Tilt=HDT). Die strenge Einhaltung dieser Form der Bettruhe führt zu vergleichbaren physiologischen Auswirkungen im menschlichen Körper wie sie in realer Schwerelosigkeit beobachtet werden. Bei der VaPER-Studie wurde dieses Modell der Bettruhe nun mit erhöhtem CO2-Gehalt (0,5%) in der Raumluft kombiniert. Auf der ISS, der Internationalen Weltraumstation, herrschen generell hohe Kohlendioxid-Konzentrationen vor, diese können bis zu 0,7% betragen (zum Vergleich: die CO2- Konzentration in der Erdatmosphäre liegt bei 0,04%). Fragestellung: Erhöhte CO2-Konzentrationen (Hyperkapnie) in Mikrogravitation verstärken die zerebrale Durchblutung, die das intrakraniale Blutvolumen (2, 3) und den intrakraniellen Druck (4) erhöhen können. Wenn nun erhöhte CO2-Konzentrationen, wie auf der ISS üblich, zusätzlichen Einfluss auf die durch Schwerlosigkeit bedingte kraniale Flüssigkeitsverschiebung haben, könnte dadurch der intrakraniale Druck und damit das Risiko der Entstehung des SANS ggf. weiter erhöht werden. Im Gegensatz zu echter Schwerelosigkeit wirkt in HDT-Bettruhe nach wie vor der Gravitationsvektor, was zu abweichenden physiologischen Effekten führen kann. Bei Studien in Kopftieflage konnten bisher keine zerebralen oder ophthalmologischen Befunde wie bei von SANS betroffenen Astronauten beobachtet werden. Möglicherweise reicht aber `-6° HDT´ als Modell allein nicht aus, um diese Effekte auch am Boden zu erzeugen. Dies kann auch dadurch bedingt sein, dass Bettruhestudien-Probanden bisher generell Kissen verwendet haben, die eine Flüssigkeitsverschiebung in den Kopf möglicherweise abgeschwächt haben können. Steilere HDT-Neigungswinkel zur Erzeugung der Erhöhung des intrakranialen Blutvolumens sind bei Langzeit-Bettruhestudien nicht umsetzbar. Folglich sollte in der VaPER-Studie herausgefunden werden, ob das Bettruhemodell für SANS-bezogene Forschung verbessert werden kann, indem die CO2-Konzentration in der Atmosphäre erhöht und gleichzeitig die Bettruheposition in -6° HDT streng eingehalten wird. Methodik: Während der VaPER-Studie war den Probanden so erstmals keine Kissennutzung erlaubt, mit Ausnahme eines sehr dünnen Kissens beim Liegen auf der Seite. Die Probanden wurden während der gesamten Bettruhe durchgehend 24 Stunden kameraüberwacht und lückenlos auf strenge Einhaltung kontrolliert. Für die erfolgreiche Durchführung von Bettruhestudien ist die Adhärenz der Probanden äußerst wichtig. Voraussetzung hierfür ist u.a. ein sorgfältiges und umfassendes Screening der Studien-Bewerber vor Studieneinschluss, auch in Bezug auf psychologische Aspekte. Zum anderen ist neben der umfangreichen medizinischen Betreuung und der hohen wissenschaftlichen Expertise der beteiligtenExperimentatoren die Qualität der operationellen Umsetzung für die Durchführung von Langzeitbettruhestudien von großer Bedeutung. So ist in der hochmodern und vielseitig ausgestatteten Großforschungsanlage :envihab des Instituts für Luft- und Raumfahrtmedizin des DLR auch eine gute soziale Atmosphäre während der stationären Phase der Bettruhestudien für deren Erfolg essentiell, was die sehr niedrige Abbruchrate der Studienteilnehmer seit Jahren beweist und die durch die DLR Mitarbeiter in besonderem Maße umgesetzt wird. Schlussfolgerungen: Während der gesamten Studie zeigten alle Probanden eine sehr hohe Adhärenz und hielten die strikte -6° Kopftieflage ohne Einschränkungen ein. Die strikte -6° Kopftieflage verbunden mit der Erhöhung der CO2-Konzentration in der Raumluft auf 0,5% führte somit zu einer Verbesserung des Modells zur Erforschung der Effekte von Schwerelosigkeit. Zukünftige Studien müssen zeigen, ob allein strenge -6°- HDT-Bettruhe, Hyperkapnie oder beides in Kombination SANS-ähnliche Effekte hervorrufen, wie sie auch vereinzelt bei der VaPER-Studie beobachtet wurden.

Human space exploration needs stable life support systems for the supply of oxygen, water and food for each human explorer due to long term missions. The most promising approach for building stable life support systems is a combination of physico-chemical and biological systems. These hybrid systems combine the reliability of physico-chemical and the sustainability of biological life support systems. Also the disadvantages, which are the finite resources of physico-chemical and the imperfect reliability of biological systems, are mutually balanced. To improve the reliability of biological life support systems, a combination of different biological systems may stabilize the whole approach during long term operations. The satellite mission Eu:CROPIS (Euglena gracilis: Combined Regenerative Organic-food Production In Space) is a testbed for investigating the behavior of combined biological life support systems under the influence of altered gravity, here, Lunar and Martian gravity. The core systems are a biological trickle filter for processing urine into a fertilizer solution via nitrification and Euglena gracilis, a photosynthetic protist which is able to produce oxygen and biomass while protecting the whole system against high ammonia concentrations.

Background: Space motion sickness (SMS) is the most relevant medical problem during the first days in microgravity. Studies addressing pathophysiology in space face severe technical challenges and microgravity is frequently simulated using the 6° head-down tilt bed rest test (HDT). Aim: We were aiming to test whether SMS could be simulated by HDT, identify related changes in gastrointestinal physiology and test for beneficial effects of exercise interventions. Methods: HDT was performed in ten healthy individuals. Each individual was tested in three study campaigns varying by a 30-min daily exercise intervention of either standing, an upright exercise regimen, or no intervention. Gastrointestinal symptoms, stool characteristics, gastric emptying time, and small intestinal transit were assessed using standardized questionnaires, 13C octanoate breath test, and H2 lactulose breath test, respectively, before and at day 2 and 5 of HDT. Results: Individuals described no or minimal gastrointestinal symptoms during HDT. Gastric emptying remained unchanged relative to baseline data collection (BDC). At day 2 of HDT the H2 peak of the lactulose test appeared earlier (mean±standard error for BDC-1, HDT2, HDT5: 198±7, 139±18, 183±10min; p:0.040), indicating accelerated small intestinal transit. Furthermore, during HDT, stool was softer and stool mass increased (BDC: 47±6, HDT: 91±12, recovery: 53±8g/day; p:0.014), indicating accelerated colonic transit. Exercise interventions had no effect. Conclusion: HDT did not induce symptoms of SMS. During HDT, gastric emptying remained unchanged, but small and large intestinal transit was accelerated.

Technical Report / Hochschule Bonn-Rhein-Sieg University of Applied Sciences, Department of Computer Science, 02-2015

The purpose of this study was to compare the LBNP tolerance between genders. Twenty healthy subjects (8 men, 12 women) were exposed to 10 min of 45mmHg LBNP. Baseline was taken in the sitting and supine positions. Finger blood pressure and heart rate (R) were recorded continuously. Stroke volume (SV), cardiac Output (CO) and total peripheral resistance (TPR) were calculated by a pulse contour method. Baseline cardiovascular variables were similar in all females, independently of the menstrual cycle Phase and they were considered as one group. Seven of 8 men and 7 of 12 women completed the 10 min of LBNP. Non-finishers (n=6) increased heart rate, decreased systolic blood pressure, mean blood pressure, calculated SV and CO in comparison with the Finisher (n=14) group (p

Aims Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known. Methods We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure (90 minutes) in supine position [protocol 1, artificial gravity exposure], or 2) lay supine on the centrifuge for 90 minutes in supine position without AG exposure [protocol 2, control]. The AG training protocol was individualized, by first determining each subject’s maximum tolerable G load, and then exposing them to 45 minutes of ramp training at sub-presyncopal levels. Results Both sexes had improved OTL (14 minutes vs 11 minutes, p < 0.0019) following AG exposure. When cardiovascular (CV) variables at presyncope in the control test were compared with the CV variables at the same tilt-test time (isotime) during post-centrifuge, higher blood pressure, stroke volume and cardiac output and similar heart rates and peripheral resistance were found post-centrifuge. Conclusions These data suggest a better-maintained central circulating blood volume post-centrifugation across gender and provide an integrated insight into mechanisms of blood pressure regulation and the possible implementation of in-flight AG countermeasure profiles during spaceflights.

High resolution mapping systems follow the trend to smaller ground sample distances (GSD) making use of the best technology available at the given time. From the 80 m GSD of ERTS in 1972, the GSD now approached 1 m and even less for civil applications. Mass and power consumption of spacecrafts and imaging instruments follow similar trends in conjunction with the immense improvements in very divers fields of technology. SAR systems are an alternative to passive optical systems; they also benefit from the technology improvements. But the most promising prospects for high resolution mapping with small satellites are connected with passive optical systems. The paper tries to give a MTF based metrics and analytical method to assess how far we can go with decreasing instrument size and decreasing the GSD at the same time and what features the spacecraft needs to provide. In this context the paper deals with such important parameters for topographic mapping with small satellites like spatial resolution, radiometry, pointing accuracy and stability. The parameters are derived from a MTF based metrics. It is shown that the imagers as well as the spacecraft bus need to follow certain rules to allow high resolution imaging aboard of small satellites.

This article describes the thematic and organizational approach of the DLR Transport Program’s research project “Transport and the Environment” (Verkehrsentwicklung und Umwelt, VEU). It illuminates the research approach, which employs scenario techniques to achieve a common understanding and a framework for the project. Establishing a platform for scientific exchange, VEU clearly facilitates the interdisciplinary integration of research on mobility within the DLR and its partner institutes. A set of transport scenarios for Germany and Europe (time horizon 2040), which are presented in greater detail in this article, is used in this respect and aims to provide answers for pressing societal questions.