Search

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

Vertical jumping power declines with advancing age, which is theoretically explicable by loss of muscle mass and increases in body fat. However, the results of previous cross-sectional studies remain inconsistent on these relationships. The present study included 256 masters athletes who competed at the 2018 track and field world championships in Málaga, Spain. We assessed body composition with bioelectrical impedance (Inbody S10) and vertical jumping power with a Leonardo ground reaction force platform. Relationships between age, jumping power, and body composition were analyzed by correlation and regression analyses. Hierarchical multiple regression analysis was used to evaluate effects of each factor on vertical jumping power. Age-related rates of decreases in maximal power and jump height were similar between male and female athletes. Percent fat-free mass and percent body fat were negatively and positively, respectively, associated with age in masters athletes and were comparable to those previously observed in the general population. Moreover, these effects in body composition can, to a great extent, explain the age-related decline in jumping power, an effect that seems at least partly independent of age. Finally, the multiple regression model to determine independent predictors of vertical jump performance yielded an overall R2 value of 0.75 with the inclusion of (1) athletic specialization in power events, (2) percent fat-free mass, and (3) phase angle. However, partial regression yielded significant effects of age, but not gender, on peak power, even when adjusting for athletic specialization, percent fat-free mass, and phase angle. We concluded that loss of skeletal muscle mass and changes in bio-impedance phase angle are important contributors to the age-related reduction in anaerobic power, even in adults who maintain high levels of physical activity into old age. However, age per se remains a significant predictor of vertical jump performance, further demonstrating deteriorated muscle quality at old age (sarcosthenia).

Resting energy expenditure (REE) is determined mainly by fat-free mass (FFM). FFM depends also on daily physical activity. REE normally decreases with increased age due to decreases in FFM and physical activity. Measuring REE is essential for estimating total energy expenditure. As such, there are a number of different equations in use to predict REE. In recent years, an increasing number of older adults continue to participate in competitive sports creating the surge of master athletes. It is currently unclear if these equations developed primarily for the general population are also valid for highly active, older master athletes. Therefore, we tested the validity of six commonly-used equations for predicting REE in master athletes. In conjunction with the World Masters Athletic Championship in Malaga, Spain, we measured REE in 113 master athletes by indirect calorimetry. The most commonly used equations to predict REE [Harris & Benedict (H&B), World Health Organization (WHO), Müller (MÜL), Müller-FFM (MÜL-FFM), Cunningham (CUN), and De Lorenzo (LOR)] were tested for their accuracies. The influences of age, sex, height, body weight, FFM, training hours per week, phase angle, ambient temperature, and athletic specialization on REE were determined. All estimated REEs for the general population differed significantly from the measured ones (H&B, WHO, MÜL, MÜL-FFM, CUN, all p < 0.005). The equation put forward by De Lorenzo provided the most accurate prediction of REE for master athletes, closely followed by FFM-based Cunningham’s equation. The accuracy of the remaining commonly-used prediction equations to estimate REE in master athletes are less accurate. Body weight (p < 0.001), FFM (p < 0.001), FM (p = 0.007), sex (p = 0.045) and interestingly temperature (p = 0.004) are the significant predictors of REE. We conclude that REE in master athletes is primarily determined by body composition and ambient temperature. Our study provides a first estimate of energy requirements for master athletes in order to cover adequately athletes’ energy and nutrient requirements to maintain their health status and physical performance.

There is controversy whether a lifetime of heavy resistance training, providing pressure-overload, is harmful for left ventricular function. We compared left ventricular dimensions and function in elite Masters athletes involved in throwing events (requiring strength; n = 21, seven females, 60 ± 14 years) to those involved in endurance events (n = 65, 25 females, 59 ± 10 years) and sprinting (n = 68, 21 females, 57 ± 13 years) at the 2018 World Masters Athletic Championships. Left ventricular dimensions and function were assessed with B-mode ultrasound and Doppler. The ratio of left ventricular early diastolic peak filling velocity to peak velocity during atrial contraction (E/A) across the mitral valve and the ratio of E to velocity of the E-wave (E’) across the lateral and septal mitral annulus (E/E’) were used as indexes of left ventricular diastolic function. Intra-ventricular septal wall thickness was greater in throwers compared to sprinters (11.9 ± 2.2 vs. 10.3 ± 2.3 mm; p = 0.01). Left ventricular end diastolic diameter/body surface area was higher in endurance athletes and sprinters vs. throwers (25.2 ± 3.0, 24.3 ± 3.1, and 22.0 ± 3.1 mm/m2, respectively, p < 0.01). The E/A was higher in endurance athletes and sprinters vs. throwers (1.35 ± 0.40, 1.37 ± 0.43, and 1.05 ± 0.41, respectively; p < 0.01). The E/E’ was lower in endurance athletes and sprinters vs. throwers (6.9 ± 1.8, 6.6 ± 1.9, and 8.1 ± 1.9, respectively, p < 0.05). Compared to age-matched historical controls (n > 1,000; E/A = 1.06; E/E’ = 7.5), left ventricular diastolic function was not different in throwers, but superior in endurance athletes and sprinters (p < 0.01). Masters throwers have altered left ventricular dimensions and function vs. other athletes, but a lifetime of heavy resistance training does not appear to alter left ventricular function compared to age-matched controls.

Background: Cardiac function and morphology are known to differ between men and women. Sex differences seen with echocardiography have not been studied systematically in masters athletes. Purpose: To evaluate sex differences in cardiac structure, function and left ventricular (LV) systolic global longitudinal strain among masters athletes. Methods: This cross-sectional study comprises of 163 masters athletes (M = 109, 60 ± 12 years; F = 55, 57 ± 12 years, range 36–91 years) who participated at the 23rd World Masters Athletics Championship held in Málaga, Spain. All athletes underwent state-of-the-art echocardiography including cardiac function, morphology, strain and hemodynamic assessment. Results: Left ventricular mass was higher in male than in female athletes (174 ± 44 vs. 141 ± 36 g, p < 0.01) due to greater end-diastolic intraventricular septal, LV posterior wall and LV basal diameter. However, LV mass index did not differ between the groups. End-diastolic LV volume and right ventricular area, both indexed to bodysurface-area, were greater in men than in women (52.8 ± 11.0 vs. 46.1 ± 8.5 ml/m2, p < 0.01, 9.5 ± 2.4 vs. 8.1 ± 1.7 cm2/m2, p < 0.01). In contrast, women had higher LV systolic global longitudinal strain (-20.2 ± 2.6 vs. -18.8 ± 2.6%, p < 0.01) and LV outflow tract flow velocity (75.1 ± 11.1 vs. 71.2 ± 11.1 cm/s, p = 0.04). Systolic and diastolic blood pressure, LV ejection fraction, and stroke volume index were not different between sexes. Conclusion: Cardiac sex differences are present even among masters athletes. Lifelong exercise training does not appear to exasperate morphological difference to a point of cardiac risk or dysfunction in both male and female athletes.

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

ntroduction: The masters athlete has been proposed as a model of successful aging. Research studies investigating psychological outlook in older athletes have primarily addressed negative affects including depression, anxiety, and stress. The impact of lifelong exercise on positive affect and life satisfaction as well as sleep impairment that could impact on these psychological states is largely unknown. Methods: A series of questionnaires (general life satisfaction, positive affect, and sleeprelated impairment) were administered to 240 masters athletes participating in the World Masters Athletics Championships. Total raw scores were converted into T scores for comparison with the general population. Meaningful difference was defined by the PROMISR as one-half standard deviation from the centering sample. Results: Meaningful differences were observed for improved general life satisfaction and reduced sleep impairment for all masters athletes. Positive affect did not reach the meaningful difference threshold. No significant sex differences were found for any of the questionnaires (all p > 0.05). Similarly, no significant differences were found between endurance, sprint, and strength/power sports for general life satisfaction (p = 0.18), positive affect (p = 0.46), and sleep impairment (p = 0.77). In general, life satisfaction increased with age (r = 0.15, p = 0.02), and sleep impairment trended towards reduction with age (r = −0.13, p = 0.05). Positive affect demonstrated no correlation with age (r = 0.09, p = 0.18). Conclusion: This study demonstrates that the lifestyles of masters athletes contribute to improved general life satisfaction and reduced sleep impairment but not improved positive affect. The beneficial effects were observed irrespective of age, gender, and sporting types

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.

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.

Chronically elevated carbon dioxide (CO₂) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head-down tilt bed rest (HDTBR) in a mild hypercapnic environment ( PCO₂ = 4 mmHg), we investigated arterialized PCO₂, cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized PCO₂ was not significantly different from the pre-HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (–0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022–0.043; P < 0.001), which remained elevated by 0.021 (0.011–0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre-HDTBR levels 13 days after BR with a change of –0.001 (–0.009 to 0.007; P = 0.991).

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

Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefined endpoints before data unblinding, continuous finger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties.

Supplemental Digital Content is available in the text., Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks’ treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130–180 mm Hg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3-2H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864.

Purpose 23Na MRI demonstrated increased tissue sodium concentrations in a number of pathologies. Acute atrophy results in muscle fibre volume shrinking that may result in a relative increase of extracellular volume and might affect sodium concentration. Thus, we hypothesized that local unloading of the calf muscles would lead to a decrease in muscle volume and an increase in muscle tissue sodium concentration. Method One lower leg of 12 healthy male subjects was submitted to a 60 day long period of unloading using the Hephaistos orthosis, while the other leg served as control. 23Na MRI and 2D PD-weighted Dixon turbo spin echo were obtained from the control and orthosis leg using a 3T scanner. For quantification, a sodium reference phantom was used with 10, 20, 30, and 40 mmol/L NaCl solution. Result Tissue sodium concentration (TSC) increased as an effect of unloading in the orthosis leg. Relative increases were 17.4 ± 16.8% (P = 0.005) in gastrocnemius medialis muscle, 11.1 ± 12.5 (P = 0.037) in gastrocnemius lateralis muscle, 16.2 ± 4.7% (P < 0.001) in soleus muscle, 10.0 ± 10.5% (P = 0.009) in the ventral muscle group, and 10.7 ± 10.0% (P = 0.003) in the central muscle group, respectively. TSC in the control leg did not significantly change. In the orthosis leg, muscle volume decreased as follows: medial gastrocnemius muscle: −5.4 ± 8.3% (P = 0.043) and soleus muscle: −7.8 ± 15.0% (P = 0.043). Conclusion Unloading atrophy is associated with an increase in muscle sodium concentration. 23Na MRI is capable of detecting these rather small changes.

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.

The evidence that physical exercise lowers metabolic and cardiovascular risk is undisputed. Normobaric hypoxia training has been introduced to facilitate the effects of exercise. We tested the hypothesis that hypoxia training augments exercise-related effects. We randomized 23 men with metabolic-syndrome to single-blinded exercise at normoxia (FiO(2) 21%) or hypoxia (FiO(2) 15%). Six weeks endurance training on a treadmill, 3 days per week, over 60 min at 60% VO(2) max was required. The study included the following: (1) metabolic phenotyping by indirect calorimetry and adipose and muscle tissue microdialysis to gain insight into effects on resting, postprandial, and exercise metabolism, (2) cardiac imaging, and (3) biopsies. Primary endpoint was the change in cardiorespiratory fitness; secondary endpoints were as follows: changes in body weight, waist circumference, blood pressure, cardiac dimensions, and adipose and muscle tissue metabolism and gene expression. Our subjects reduced waist circumference and improved several cardiovascular risk markers including blood pressure. However, these effects were similar in both training groups. Cardiac dimensions were not influenced. We focused on glucose metabolism. After an oral glucose load, adipose tissue metabolism was significantly shifted to a more lipolytic state under hypoxia, whereas muscle metabolism was similar under both conditions. Postprandial energy expenditure was significantly increased under hypoxia, whereas activity energy expenditure was improved under normoxia. Gene expression was not consistently influenced by FiO(2). Adipose tissue triglyceride lipase, leptin, and hypoxia-inducible factor-alpha expression were increased by normoxia but not hypoxia.

Background: An astronaut’s body is exposed during spaceflight to the peculiar condition of weightlessness, and consequently experiences various adaptive changes, among which bone and muscle loss stand out. Although space agencies nowadays adopt numerous preventive measures against these pathologies, they are presently only able to reduce their entity but not entirely prevent their onset. Hence, alternative countermeasures are currently being investigated, in the hope that they may be more effective and efficient in this setting. Objective: The purpose of this experimental study was to assess the usefulness of a novel form of high-intensity interval training (HIIT), based on the principle of jumping, which could be used aboard the International Space Station (ISS) to prevent musculoskeletal deconditioning in astronauts. The effectiveness of the training has been determined by evaluating its ability in preventing the onset of atrophy in lumbar paraspinal muscles, and chiefly in the multifidus, over the course of a bed-rest study. Materials and Methods: Twenty-three healthy male participants, aged between 21 and 42, selected after an extensive screening procedure, were confined for ninety days in the facilities of the German Aerospace Centre in Cologne. The study was divided in three phases: a 15-day baseline measurement phase, a 60-day 6 head-down-tilt (HDT) bed-rest phase, and a 15-day recovery phase. Participants were oralrandomly allocated to the control group (CTRL, n=11) or the training group (JUMP, n=12). Subjects have been carefully monitored during the whole study, and the dimensions of their lumbar paraspinal muscles has been measured using magnetic resonance imaging at nine points in time, during and after the bed rest. Results: Subjects have tolerated the exercise well, and adherence to the planned protocol has been perfect, despite a few deviations in intensity. No significant difference in lumbar paraspinal muscles atrophy between the training and the control group has emerged at any study-date (p=0.210), whereas a significant reduction in their thickness at the end of the bed rest has been demonstrated in both Groups (-5,05%, p

In humans, muscle sympathetic nerve activity (MSNA) recordings at the peroneal nerve exhibit a stable temporal relationship between baroreceptor engagement and MSNA burst occurrence with sympathetic baroreflex (sBR) latencies ranging from 900 to 1600 ms. However, modifications of the sBR latency and determinism are not sufficiently elucidated, especially in response to a sBR challenge. We propose a method to assess sBR latency and determinism by monitoring post-stimulus time distribution (PST) of the time elapsed between R-wave, detected on the ECG, and MSNA burst occurrence. The mode of the PST (if significantly present) in the range of plausible physiological values was taken as an estimate of the sBR latency. We built a binary series coding the appearance/non-appearance of the MSNA burst associated to the R-wave. The level of sBR determinism was computed by comparing the normalized corrected conditional entropy (NCCE) over the original binary series to the NCCE computed over a surrogate series obtained via random shuffling of the original binary digits. The approach was applied to 10 healthy subjects and 5 amyotrophic lateral sclerosis (ALS) patients at rest in supine condition (REST) and during head-up tilt (TILT). In the healthy population, NCCE was found significantly lower in surrogates than in the original series (0.826±0.069 vs 0.877±0.053, p

BACKGROUND: Essential arterial hypertension is one of the main treatable cardiovascular risk factors. In Germany, approximately 13% of women and 18% of men have uncontrolled high blood pressure (≥ 140/90 mmHg). METHODS: This review is based on pertinent publications retrieved by a selective literature search in PubMed. RESULTS: Arterial hypertension is diagnosed when repeated measurements in a doctor's office yield values of 140/90 mmHg or higher. The diagnosis should be confirmed by 24-hour ambulatory blood pressure monitoring or by home measurement. Further risk factors and end-organ damage should be considered as well. According to the current European guidelines, the target blood pressure for all patients, including those with diabetes mellitus or renal failure, is

Natriuretic peptides are commonly considered cardiovascular and renal hormones. Indeed, genetic natriuretic peptide deletion promotes arterial hypertension and associated organ damage.1 Conversely, pharmacological natriuretic peptide augmentation lowers blood pressure. Less recognized is the fact that natriuretic peptides potently affect lipid and glucose metabolism. Through these metabolic actions, natriuretic peptides may provide a pathophysiological link between cardiovascular and metabolic disease. Indeed, arterial hypertension and insulin resistance or overt type 2 diabetes mellitus commonly occur in the same patients. Similarly, heart failure is associated with impaired skeletal, muscular oxidative function and insulin resistance.2,3 The review focusses on recent epidemiological, genetic, physiological, and pharmacological evidence linking the natriuretic peptide system with metabolic disease. Moreover, we discuss clinical trials evidence suggesting that natriuretic peptide modulation could be pursued further in metabolic disease prevention and treatment. ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide) are released from cardiac atria and ventricles, respectively. Both peptides are produced as preprohormones and are stored as prohormones in intracellular granules. The native peptides are released in equimolar amounts with N-terminal peptide fragments, which are more stable than the native hormones and can serve as natriuretic peptide release markers. Stretch of atrial or ventricular cardiomyocytes which can be secondary to increased sodium intake, physical exercise, or diseases associated with volume overload triggers natriuretic peptide release. Both natriuretic peptide and their N-terminal peptide fragments are clinically established heart failure biomarkers. Once released, natriuretic peptides raise renal sodium excretion, elicit vasodilation, and are the physiological antagonists of the renin-angiotensin system.4 Natriuretic peptides also attenuate sympathetic nervous system activity at least in part through interaction with central vasopressin pathways.5 ANP and BNP responses are primarily mediated by the GCA (guanylyl cyclase-coupled natriuretic peptide receptor; also known as NPR-A [natriuretic peptide receptor A]). NPR-C, which is sometimes …

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.

Background/Introduction: Endovascular baroreflex amplification (EBA) is a novel device­based therapy that has been shown to lower blood pressure (BP) in patients with resistant hypertension (RHTN) in an uncontrolled first­in­human study. It is postulated that EBA lowers BP, at least in part, by inhibiting sympathetic nerve activity (SNA). However, this has never been studied. Purpose: The aim of this study was to determine the effect of EBA on SNA and sympathetic cardiovascular reactivity. Methods: In a single­center sub­study of the CALM­DIEM study (Controlling And Lowering blood pressure with the MobiusHD – Defining Efficacy Markers), the endovascular MobiusHD device was unilaterally implanted into the carotid sinus of patients with RHTN (24­hour mean ambulatory systolic BP >130 mmHg on ≥3 antihypertensive medications, including a diuretic) without atherosclerotic carotid disease. Microneurography at the right peroneal nerve and non­invasive continuous BP measurements were performed at baseline and 3 months, after a 2­week washout of antihypertensive medications affecting sympathetic regulation. Changes in resting muscle SNA and cardiovascular responses to cold pressor testing (CPT) were determined. Results: 10 patients, mean age 52 (±8 years), 6 males, have been included in the study thus far. Of these, 8 patients had a paired measurement at baseline and 3 months. One patient has not yet reached the third month endpoint and one patient was unable to visit our clinic for measurements at 3 months. Two of the 8 paired measurements were excluded from analysis because of poor quality of muscle SNA recording and one was excluded because of frequent premature ventricular complexes. 24­hour mean ambulatory BP (n=8) decreased from 156/98 (±22/17) mmHg to 145/88 (±19/17) mmHg (p=0.028 for systolic and p=0.048 diastolic BP). Analysis of the first 5 patients to complete the study with paired data, suggests a decrease in resting muscle SNA from 38.6 (range 15.7–70.6) to 30.3 (range 5.0–65.9) bursts/min, and from 48.3 (range 21.2–81.2) to 37.9 (range 7.3–75.2) bursts/100 heartbeats, 3 months after EBA. In contrast, cardiovascular reactivity appears unaffected because MAP and HR responses to CPT did not change. Conclusion: In patients with RHTN we observed a decrease in BP and muscle SNA 3 months after EBA. The finding is consistent with attenuated central sympathetic drive and may suggest that EBA, indeed, improves sympathetic baroreflex restraint. Furthermore, the MAP and HR responses to CPT did not change, indicating that BP reactivity remains intact after EBA.

Aims. Prolonged immobilization generates cardiac deconditioning, a risk factor for cardiovascular disease: efficient countermeasures (CM) are needed to prevent it. Our aim was to assess the effectiveness of high-intensity jump training CM on aortic and mitral flow by Phase-Contrast (PC) MRI during longterm head-down (-6 degrees) bed-rest (BR). Methods. 23 male participants (29+\-6 years, 181+\-6 cm, 77+\-7 kg) were enrolled at :envihab (Koln, DLR, Germany) as part of the European Space Agency BR studies. Participants 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. PC-MRI images (3T Biograph mMR, Siemens) with interleaved three-directional velocity encoding (VENC: x and y: 80 cm/s; z: 150 cm/s) were obtained (spatial resolution 1.4 x 1.4 mm2) at the level of the aortic root, and of the mitral plane, before (PRE), after 58-days (HDT58), and on the fifth day after BR conclusion (R+4). The resulting planar magnitude data and three-directional velocity images were semi-automatically analysed to compute the following parameters: cardiac Output (CO), stroke volume (SV), flow rate (Qpeak), systolic duration and heart beat duration (RR), rapid filling (Efilling) and inflow rate (Epeak). Results. In CTRL, compared to PRE, after 58-days BR a significant (p

Purpose: Central aortic blood pressure and pulse wave velocity measurements are more predictive in terms of cardiovascular organ damage and risk compared with peripheral blood pressure. Such measurements, which have been proven useful in detecting early vascular aging on earth, have not been obtained after long term space missions. We applied an easy-to-perform, non-invasive, and wearable device to assess central blood pressure and other hemodynamic variables in cosmonauts. Methodology: We obtained oscillometric blood pressure measurement at the upper arm for determining central and peripheral blood pressure, heart rate, and pulse wave velocity (Mobil-O-Graph PWA, IEM, Germany) in eight cosmonauts before and after six months in space. In the supine position, we obtained multiple measurements at baseline (65-90 days before flight), four days (R+4) and eight days (R+8) after return. Written informed consent was given by all subjects. Results:Heart rate was 58.4±6:5 bpm at baseline, 70.3±5:2 bpm on R+4, and 66.2±9:0 bpm on R+8 (both p

Baroreflexes and peripheral chemoreflexes have a powerful effect on efferent autonomic activity making them prime suspects in the pathogenesis of cardiovascular disease and attractive treatment targets. However, the literature on their interaction is controversial, likely through inter- and intraindividual variability in cardiovascular reflex regulation. Therefore, we applied an n-of-1 Trial design to elucidate individual baroreflex-chemoreflex interactions.

In this study, we investigated: i) the effects of bed rest and a subsequent physical training program on metabolic cost (Cw), mechanical work and efficiency during walking in older and young men; ii) the mechanisms underlying the higher Cw observed in older than young men.Twenty-three healthy male subjects (N = 16 older adults, age 59.6±3.4 years; N = 7 young, age: 23.1±2.9 years) participated in this study. The subjects underwent 14 days of bed rest followed by two weeks of physical training (6 sessions). Cw, mechanical work, efficiency, and co-contraction time of proximal muscles (vastus lateralis and biceps femoris) and distal muscles (gastrocnemius medialis and tibialis anterior) were measured during walking at 0.83, 1.11, 1.39, 1.67 m·s⁻¹ before bed rest (pre-BR), after bed rest (post-BR) and after physical training (post-PT).No effects of bed rest and physical training were observed on the analysed parameters in either group. Older men showed higher Cw and lower efficiency at each speed (average +25.1 and -20.5%, P

Orthostatic intolerance has been described after prolonged bed confinement in several clinical settings. This may impact patients’ quality of life and increase risk of falls. Standing is associated with unloading of baroreceptor activity controlling heart rate (HR) and sympathetic vasomotor discharge assessed by muscle sympathetic nerve activity (MSNA). In the present study we evaluated the changes in baroreceptor response and in orthostatic tolerance induced by controlled long lasting bed rest in healthy volunteers. As part of the European Space Agency Medium-term Bed Rest protocol, eight volunteers (33 ±1yrs) were studied before and after 21-days of -6º head down bed rest (HDBR). Subjects underwent ECG, beat-by-beat blood pressure, respiratory activity and MSNA recordings during 15-minutes of 80 head-up tilt (HUT) followed by a 3-minute –10mmHg stepwise increase of lower body negative pressure, up to pre-syncope. The α index obtained in the low frequency band (0.1 Hz) by cross-spectrum analysis of RR and systolic arterial pressure (SAP) variability quantified the cardiac baroreflex sensitivity. The percentage of MSNA burst occurrence for different diastolic pressure values (grouped in bins of 1 mmHg) was assessed. The slope of the regression line between MSNA Bursts % and diastolic pressure was assumed to represent the gain of sympathetic baroreflex control (sBRS). the subjects orthostatic tolerance was decreased after HDBR(12±0.6min) compared to baseline (21±0.6min). In the supine position HR, SAP and α index were unchanged before and after HDBR. During HUT, HR and SAP were unmodified, α index was lower after (3.4±0.7) compared to before HDBR (6.4±1.0). While supine, sBRS was lower after (-2.9±1.5 %mmHg) compared to before HDBR (-6.0±1.1 %/mmHg). Similarly, during HUT sBRS was lower after HDBR (-2.2±0.6 %/mmHg) compared to before (-4.4±0.4%mmHg). These data suggest that prolonged bed confinement decreased the overall baroreceptor sensitivity.These alterations may be involved in the reduction of orthostatic tolerance.

DLR +30°AMS-Studie: Einfluss von nächtlicher Oberkörperhochlagerung auf die akute Höhenkrankheit und die Schlafqualität in großer Höhe – Studiendesign und erste Ergebnisse Einleitung: Bergsteiger und Astronauten leben und arbeiten in einer herausfordernden Umwelt mit einer Vielzahl an Gefahren für die menschliche Gesundheit und Leistungsfähigkeit. Bei Bergsteigern führt die hypobare Hypoxie zu einer Vasodilatation zerebraler Gefäße. Durch Ödembildung und Venokompression steigt der intrakranielle Druck und es kommt zur akuten Bergkrankheit (ABK). Schlafen in der Höhe in horizontaler Position schränkt den venösen Abfluss weiter ein. Bei Astronauten führt die Schwerelosigkeit zu einer venösen Stauung des Kopfes, wodurch es zu Kopfschmerzen und Augenveränderungen kommen kann. Eine nicht medikamentöse Prophylaxe gegen einen erhöhten venösen intrakraniellen Druck könnte die Gesundheit 55. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Luft- und Raumfahrtmedizin e.V. Abstracts und Programmheft 2017 Seite 41 beider Kollektive schützen und medizinische Hürden auf dem Weg zum Mars abbauen. Primäre Hypothese: Nächtliche 30°- Oberkörperhochlagerung in der Höhe reduziert ABK in Bergsteigern im Vergleich zur üblichen horizontalen Schlafposition. Sekundäre Hypothese: Nächtliche 30°- Oberkörperhochlagerung in der Höhe verbessert die Schlafqualität in Bergsteigern im Vergleich zur üblichen horizontalen Schlafposition. Studiendesign: Eine randomisiertkontrollierte monozentrische Studie. Probanden: 130 Bergsteiger, welche nach aktivem Aufstieg eine Nacht auf der Capanna Regina Margherita (CRM) auf 4554 m in den Walliser Alpen verbringen. Einschlusskriterium ist das Vorhandensein ABK am Abend des Ankunftstages auf der CRM, definiert als Lake Louise Score > 3 und < 12 Punkten (1). Primä- rer Studien-Endpunkt ist die Differenz ABK in der Gruppe +30° gegen die Gruppe „horizontal“ gemessen mit dem AMS-C Score des Environmental Symptom Questionnaire III (2). Sekundärer Endpunkt ist die baselineadaptierte Schlafqualität (3). Explorative Endpunkte sind die arterielle Sauerstoffsättigung und die Herzfrequenz. Ergebnisse: Die Studie wird im August 2017 durchgeführt. Es werden erste vorläufige Ergebnisse präsentiert.

Einleitung: Ein schneller Aufstieg in große Höhe führt in den ersten 2-5 Tagen zur akuten Höhenkrankheit (AHK), deren Mechanismen nur unzureichend verstanden sind. In Tierund klinischen Studien kam es durch Hypoxie und Inflammation zum Zusammenbruch der Gefäßbarriere bestehend aus einer endothelialen Mikroschicht aus Proteoglykanen (Glycocalyx). Daraus folgte eine erhöhte Gefäßpermeabilität mit Ödembildung und Proteinurie. Die Glycocalyx erholte sich in einer dieser Studien innerhalb von 5 Tagen und zeigte damit eine vergleichbare zeitliche Dynamik wie die AHK. Im Rahmen der AHK ist das Verhalten der endothelialen Glycocalyx allerdings bisher nicht erforscht worden. Hypothesen: Eine 6-tägige Höhenexposition führt zu Hypoxämie, Albuminurie, Bildung peripherer Ödeme und einer Erhöhung der Blutkonzentration der (endothelialen) Glycocalyxfragmente Syndecan-1, Heparansulfat, und Hyaluronan und des Inflammationsmarkers CRP im Vergleich zu den Ausgangswerten in Meereshöhe. Methodik: Aktiver, zweitägiger Aufstieg von 9 gesunden Probanden (4�) zur Capanna Regina Margherita (4554 m, Monte Rosa Massiv, Italien) mit anschließendem 6-tägigem Aufenthalt. Tägliche Messung der peripheren Sauerstoffsättigung und Quantifizierung der akuten Höhenkrankheit mittels Lake Louise Fragebogen (LLS), tägliche 24hUrinsammlung zur quantitativen Bestimmung der Albuminausscheidung und tägliche Blutabnahmen zur späteren Analyse der genannten Glycocalyxfragmente und des CRP. Ergebnisse: Die Höhenexposition führte im Probandenkollektiv nach 48 h zu einer maximalen Hypoxämie mit einer peripheren Sättigung von 76 ±4% und zur Höhenkrankheit (max. 5,5 ±1,8 Punkte im LLS nach der ersten Nacht in 4554 m). Alle Probanden zeigten klinisch periphere Ödeme. Am 5. Tag in der Höhe war das Albumin im Urin signifikant gegenüber dem Ausgangswert in 70 Meter über Meereshöhe erhöht. Syndecan-1, Heparansulfat und Hyaluronan waren in der Höhe signifikant gegenüber den Ausgangswerten erhöht. Schlussfolgerungen: Die in dieser Höhenstudie gefundenen peripheren Ödeme in Kombination mit der erhöhten Albuminausscheidung im Urin, sprechen für eine Erhöhung der Durchlässigkeit der Gefäßbarriere. Die erhöhte Konzentration an Glycocalyx-Bestandteilen im Blut in der Höhe deutet auf eine Fragmentierung der endothelialen Glycocalyx als Pathomechanismus hin. Die bekannten Trigger der Glycocalyx-Fragmentierung, Hypoxämie und eine systemische Inflammationsreaktion, könnten in diesem Fall eine Rolle gespielt haben. Förderung: Die Studie wurde durch programmatische Mittel des DLR Instituts für Luft- und Raumfahrtmedizin und durch Fördermittel der Deutschen Gesellschaft für Berg- und Expeditionsmedizin (BExMed) finanziert.

More than half of astronauts present with significant neuro-ophthalmic findings during 6-month missions onboard the International Space Station. Although the underlying cause of this Microgravity Ocular Syndrome is currently unknown, alterations in cerebrospinal fluid dynamics within the optic nerve sheath may play a role. In the presented study, diffusion tensor imaging was used to assess changes in diffusivity of the optic nerve and its surrounding sheath during head-down tilt, a ground-based model of microgravity. Nine healthy male subjects (mean age ± SD: 25 ± 2.4 years; mean body mass index ± SD: 24.1 ± 2.4 kg/m2) underwent 5 head-down tilt conditions: −6°,−12°, −18°,−12° and 1% CO2, and −12° and lower body negative pressure. Mean diffusivity, fractional anisotropy, axial diffusivity, radial diffusivity were quantified in the left and right optic nerves and surrounding sheaths at supine baseline and after 4.5 h head-down tilt for each condition. In the optic nerve sheath, mean diffusivity was increased with all head-down tilt conditions by (Best Linear Unbiased Predictors) 0.147 (SE: 0.04) × 10−3 mm2/s (P 0.3). These findings could be due to increased perioptic cerebral spinal fluid hydrodynamics during head-down tilt, as well as increased cerebral spinal fluid volume and movement within the optic nerve sheath., Vision: Microgravity may alter optic nerve and surrounding sheath Changes to the optic nerve and surrounding sheath during microgravity could explain why space flight is harmful to an astronaut’s vision. Darius Gerlach from the German Aerospace Center in Cologne and colleagues studied the tissue architecture of the optic nerve and its surrounding sheath in nine healthy men who experienced head-down tilt, a commonly used ground-based model of weightlessness. Using a neuroimaging technique called diffusion tensor imaging, the researchers documented fluid dynamic changes wrought by the microgravity-like conditions that could be due to alterations in the volume and movement of cerebrospinal fluid within and around the optic nerve. The findings may help explain why many astronauts experience poorer vision after long-duration space flights, although more work is needed to explore the effects of true microgravity on the visual system.

Objective: Hypoxia is the main trigger of acute mountain sickness (AMS). However it is not the cause of the actual symptoms of AMS. The biochemical mechanisms underlying the AMS development are not well understood what leads to a high uncertainty regarding the likeliness of AMS development in astronauts living in future moderate hypobaric hypoxic habitats on Mars or moon. The hypothesis of the EFA study (Edema Formation in the High Alps) was that hypoxia triggered inflammatory processes lead to a breakdown of the capillary barrier and edema formation in vulnerable tissues as the brain. Methods: 11 subjects (5 women) ascended within 48 h from 1154 m to the Capanna Regina Margherita in 4554 m. Brain magnetic resonance imaging (MRI) was performed at sea level before the altitude exposure and within the first 12 h after descent. MRI included amongst others an anatomical 3D volumetric T1-weighted MPRAGE (magnetization-prepared rapid acquisition of gradient echo) scan, a susceptibility weighted gradient echo sequence, T2 weighted spin echo sequences and a diffusion weighted sequence to gain an apparent diffusion coefficient mapping and a trace image to test for volume changes of the different brain compartments, for hypoxic triggered brain edema and for micro-bleedings. Baseline measurements were performed at the DLR MRI lab in Cologne (77 m) whereas post line measurements were performed at the MRI department of the German Air Force in Fürstenfeldbruck (517 m) by applying identical sequences at both centers. Results: Neither mean global intracranial volume (p=7.97) nor mean volumes of the particular brain compartments grey (p=0.279) and white matter (p=0.758) or cerebrospinal fluid (p=0.586) showed any significant differences after the altitude exposure with respect to baseline. However 6 days of altitude exposure lead to the exacerbation of pre-existing white matter lesions in one subject and the occurrence of a local hypoxic edema in the splenium of a second subjects in the sense of a reversible splenial lesion syndrome (RESLES) (1, 2). Conclusion: Contradictory to the current literature (3) we were not able to show a general volume gain of the intracranial compartments after high altitude adaptation. However our findings of white matter lesions (4) and RESLES in two subjects not presenting any symptoms of a high altitude cerebral edema (HACE) have, as far as we know, not been described before (5).

Einleitung: Seit etwa 10 Jahren ist bekannt, dass es nach Langzeitaufenthalten im Weltraum zu charakteristischen Veränderungen der Augen kommt, welche u.a. Hyperopie, Bulbus-Verkürzung und Aufweitung der Sehnervenscheide umfassen. Zusätzlich ist bei einer Reihe von Astronauten ein erhöhter Liquor-Eröffnungsdruck nach Rückkehr auf die Erde festgestellt worden. Insbesondere die letzten beiden Befunde legen nahe, dass den Augenveränderungen ein erhöhter intrakranieller Druck zugrunde liegt. Kopfschmerz, Übelkeit und Schlafstörungen, welche oft von Astronauten berichtet werden, könnten zumindest teilweise durch Hirndruck verursacht sein. Und auch die vermutete kognitive Leistungseinbuße in der Schwerelosigkeit wäre theoretisch durch erhöhten Hirndruck erklärbar. Es stellt sich deshalb die Frage, ob es in der Schwerelosigkeit in der Tat zu erhöhtem Hirndruck kommt, und welche physiologischen Mechanismen an der Erhöhung beteiligt sein könnten. Ergebnisse aus dem Weltraum: Bei Astronauten sind kopfwärts gerichtete Flüssigkeitsverschiebungen seit langem bekannt, die u.a. zum sogenannten ‚puffy face‘ führen. Allerdings sind die Ursachen hierfür nicht verstanden. Eine mögliche Erklärung wäre jugular-venöse Stauung, welche auch jüngst an Astronauten beobachtet worden ist. Diese könnte wiederum durch Verlust der Retraktionskräfte am Thorax, bedingt durch den ‚Gewichtsverlust‘ der Eingeweide, und damit durch eine Abflussbehinderung in den venae subclaviae verursacht sein. Erhöhter Druck im Sinus sagitalis führt nach dem gegenwärtigen Verständnis der Liquor-Zirkulation zur Verminderung der Liquor-Resorption, und damit zum erhöhten Hirndruck. An Ratten wurden nach Aufenthalt in der Schwerelosigkeit Veränderungen des plexus choroideus gemessen,welche gut zu erhöhtem Hirndruck passen würden. Demgegenüber sei aber auch erwähnt, dass invasive Messungen des Hirndrucks im Parabelflug ein Erniedrigung und keine Erhöhung gezeigt haben. Dieser Effekt ist wegen seines raschen Eintrittes (binnen Sekunden) aber wohl eher physikalischanatomisch als physiologisch zu erklären. Schließich sei noch erwähnt, dass die erhöhte CO2-Konzentration in ursächlichem Zusammenhang zum Auftreten von Kopfschmerzen auf der Raumstation steht. Ergebnisse aus bodengestützten Studien: In der Abteilung ‚Weltraumphysiologie‘ haben in den Vergangenen Jahren in einer Reihe von Studien das Modell der Kopftieflage genutzt, um für die Raumfahrt relevante Effekte der kranialen Flüssigkeitsregulation zu studieren. Die wichtigsten Ergebnisse aus diesen Arbeiten waren: 1) Kopftieflage führt zu venöser Stauung und Reduktion der arteriellen Durchblutung; 2) Kopftieflage führt zur vermehrten Ansammlung von Liquor im Kranium; 3) letzterer Effekt kann durch lower body negative pressure unterbunden werden. 4) Kopftieflage führt, vermutlich durch kraniale Minderdurchblutung, zur Reduktion der kognitiven Leistungsfähigkeit. Schlussfolgerungen: Das Thema Hirndruck ist für die Gesundheit und Leistungsfähigkeit von Astronauten vermutlich von größerer Bedeutung als bisher angenommen. Die Ergebnisse aus den bodengestützten Studien untermauern die mögliche Rolle von ugularvenöser Stauung.

Weightlessness during long-term space flight over 6-12 months leads to complex individual cardiovascular adaptation. The initial central blood volume expansion followed by a loss of plasma volume is accompanied by changes in vascular mechanoreceptor loads and responsive-ness, altered autonomic reflex control of heart rate and blood pressure, and hormonal changes in the long run. Hence, function and structure of the heart and blood vessels may change. Hemodynamic data obtained during short- and long-term space flight may indicate that the adaptation process resembles ageing of the cardiovascular system characterized by decreased diastolic blood pressure, increased central sympathetic nerve traffic and increased arterial pulse wave velocity. Experiments during parabolic flights in supine position suggest, that stroke volume does not change during transitions between µ-g and 1-g. We tested a novel method of pulse wave separation based on simple oscillometric brachial cuff waveform reading to investigate pulse wave reflection during acute weightlessness in healthy subjects. We hypothesized that the wave reflection magnitude (RM) remains unaltered during parabolic flights in supine position.

Experiences in long-term flights on space stations have provided evidence that the longer the space mission, the more important become psychological factors, the required knowledge about these factors, and their changes. During the flight, when psychological monitoring is most important and needed, it becomes mostly difficult. The methods used should be objective, non-obtrusive, non-disrupting, mission related, useful for crew itself (immediate expert-system based feedback) as well as that they should be neither tedious nor artificial nor abstract, so that they will not be avoided but accepted by the crew. There is a heightened need for new measurements and methods which are objective, reliable, computerized, continuously, or at least repeatedly, applicable in order to achieve – in a perfect setting - monitoring of nearly all behavior and performances during a mission. Irrespective if and how psychological monitoring is to be fully understood, it must first be viewed as an essential support tool for the crew, parallel to the technical monitoring systems e.g. of fuel and water quality. Rigorous selection of the crew favors those who are tough, enduring, well-trained, performance-oriented, and unaccustomed to “needing” the help of psychologists. Although these participants are honest in subjective self-evaluation, they tend to exhibit repression. This requires re-thinking, and re-evaluation of psychological methodology. Presently, psychological monitoring focuses usually only on performance in special and common tasks, for example docking training, or have a scientific background. We still only have limited methods to objectively monitor all the indicators mentioned. Sensitive observation and private conversation based on a trusting personal relation between ground and crew remain the most important. Likewise, the monitoring of group cohesion and group conflict should focus on the group dynamics, cultural life, events, group activities, sub-group separation. For an autonomous decision making of the crew, an independent computerized support system on board could be a great assistance not only for technical problems. There are first successful and promising attempts in video face emotion analysis. Voice frequency analysis is a very promising approach for space psychology. Voice cross analysis could indicate the common and individual amounts of communication but also the emotional states and reactions of the speakers. A wireless group structure monitoring could provide information about the dynamics of the crew structure during the mission. Work sample analysis represents an already well established method and is used as a routine monitoring. Really mission relevant skills (e.g. the hand controlled docking of a space craft on a space station or catching a free flying object by means of a hand controlled robot arm) are refreshed and trained during the mission, thus, providing information about the proficiency of the operators and about their actual motivational state. If this professional monitoring is associated with a physiological strain assessment, an indirect monitoring of the psychophysiological state is provided. It seems possible to implement features of embedded testing of fundamental cognitive functions into these refreshment trainers. However, areas such as automated daily duty analysis, analysis of the cooperation quality during shared duties, analysis of readiness and progress in coping with expert-system feedback or learning new things (e.g. the language of crew mates or new skills) as well as a spare time use analysis are currently only at the proposal level.

Einleitung: Checklisten sind in der Luftfahrt ein bewährtes Instrument um die Sicherheit zu erhöhen. Der Einsatz über viele Jahrzehnte hat gezeigt, dass sie effektiv die Zahl der Fehler verringern können, die Piloten im „komplexen System“ Flugzeug begehen. Sicherheits-Checklisten werden zunehmend auch im klinischen Betrieb eingesetzt, aber bisher nicht in der biomedizinischen Forschung. Fragestellung: Ziel war es, die etablierten Checklist-Konzepte aus der Luftfahrt und der Medizin zu kombinieren und an die speziellen Bedürfnisse während biomedizinischen Studien anzupassen. Untersucht wurde, wie effektiv die Checklisten die Probandensicherheit erhöhen und zur Qualität der wissenschaftlichen Daten beitragen. Methodik: Während einer 89-tägigen Bettruhestudie mit insgesamt 12 Probanden wurde bei Beginn protokolliert, welche Fehler bei den Kernexperimenten Fahrrad Spiroergometrie, Kipptisch und Muskelbiopsie von den Experimentatoren ohne Checklisten gemacht wurden. Die elektronischen Checklisten wurden zum Ende der Studie eingeführt und bei den gleichen Experimenten getestet. Ergebnisse: Bei allen drei Experimenten zeigte sich ein signifikanter Rückgang an Fehlern und damit eine deutliche Steigerung der Probandensicherheit und der Datenqualität. Schlussfolgerungen: Es hat sich gezeigt, dass Checklisten in der biomedizinischen Forschung sinnvoll eingesetzt werden können. Wichtig ist, die Benutzer der Liste bei der Planung mit einzubeziehen und die zu checkenden Punkte zu selektieren, um die Akzeptanz der Checklisten zu erhöhen.

Einleitung: Die Bedingungen eines Raumfluges beeinflussen die Hämostase. Ebenso scheinen thrombozytäre Mikropartikel (platelet-derived microparticle, PMP) die menschliche Blutgerinnung zu verändern. Es ist unklar, inwieweit erhöhte Schwerkräfte einen Einfluss auf thrombozytäre Mikropartikel ausüben. Fragestellung: Unter Berücksichtigung der aktuellen Studienlage ist es unklar, wie sich veränderte Gravitationskräfte auf die menschliche Hämostase auswirken. Hinweise aus Studien an Tiermodellen, Zellkulturstudien und Fallberichten deuten jedoch darauf hin, dass erhöhte Schwerkraft das menschliche Gerinnungssystem im Sinne einer Hyperkoagulabilität aktiviert. In diesem Zusammenhang scheinen PMP einen prokoagulatorischen Effekt zu vermitteln. Inwieweit sich erhöhte g-Kräfte auf PMP auswirken, war die Fragestellung der vorliegenden Studie. Methodik: Es wurden Messungen auf der humanen Langarm-Zentrifuge des DLR in Köln durchgeführt. Hierbei wurde an 20 gesunden Probanden der Einfluss einer 15-minütigen Hyper-g- Phase von 3 g in aufrecht sitzender Position untersucht. Venöses Blut wurde an drei definierten Zeitpunkten abgenommen: vor der Hyper-g Phase, unmittelbar nach und im Anschluss an eine 30-minütigen Ruhezeit. Die gewonnenen Blutproben wurden mittels erweiterten gerinnungsphysiologischen Messungen und auf Mikropartikel mittels Durchflusszytometrie (FACS) untersucht. Ergebnisse: Die gewonnenen Daten zeigten eine Aktivierung der Hämostase, unmittelbar im Anschluss an die Zentrifugation. Es kam zu einem signifikanten Anstieg von CD 42b, CD 62p und CD 61-positiven PMP. Schlussfolgerungen: Während Hypergravitation wird eine vermehrte Anzahl an prothrombogenen Mikropartikeln gebildet. Frühere Daten haben bereits eine Aktivierung des plasmatischen Gerinnungssystems in Hypergravitation gezeigt. Daraus ergibt sich die Schlussfolgerung, dass sich Personen mit einer Prädisposition für thrombembolische Ereignisse nur nach individueller medizinischer Risikoabwägung erhöhten Schwerkräften aussetzen sollten.

Einleitung: In Parabelflügen kommt es auf Grund der Übergänge zwischen doppelter Schwerkraft und Schwerelosigkeit zu Volumenverschiebungen innerhalb des Gefäßsystems und somit auch zu einer veränderten Pumpleistung des Herzens. Die Systolischen Zeitintervalle bieten eine nichtinvasive Variante zur Beurteilung der kardialen Funktion. Fragestellung: Wie verhalten sich die Systolischen Zeitintervalle im Parabelflug? Können Sie die Volumenverschiebungen widerspiegeln? Methodik: Zur Aufzeichnung der Systolischen Zeitintervalle wurde eine Kombination aus EKG, Phonokardiographie und kontinuierlichem Fingerblutdruck verwendet. Fünf Probanden nahmen an dem Experiment teil und verbrachten jeweils 15 Parabeln liegender und 15 Parabeln stehender Körperposition. Ergebnisse: Erste Ergebnisse zeigen, dass die elektromechanische Systole nach einem stehenden Übergang in Schwerelosigkeit deutlich kürzer ist als nach einem Liegenden. Auch das Verhältnis zwischen Präejektionsperiode und linksventrikulärer Auswurfszeit nimmt nach einem stehenden Übergang deutlich ab, was auf eine erhöhte Vorlast und eine gesteigerte Inotropie hindeutet. Schlussfolgerungen: Die Systolischen Zeitintervalle können die Volumenverschiebungen im Parabelflug widerspiegeln. Da sich diese Intervalle nichtinvasiv aufzeichnen lassen, eignen Sie sich hervorragend für das Gebiet der Raumfahrtmedizin.