Magnetic Resonance Investigation of the Human Brain after 6 Days of Acclimatization to 4554 m - Preliminary Results of the EFA study -

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)

Wave reflection, assessed by use of the ARCSolver Algorithm for pulse wave separation, is reduced under acute µg conditions in parabolic flight

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

Limited utility of self-made oxygen generators assembled from everyday commodities during the COVID-19 pandemic

The current COVID-19 pandemic has aggravated pre-existing oxygen supply gaps all over the world. In fact, oxygen shortages occurred in affluent areas with highly developed healthcare systems. The state-of-affairs created much suffering and resulted in potentially preventable deaths. Meanwhile, several international activities have been initiated to improve oxygen avail- ability in the long-term by creating new networks of oxygen plants and supply channels. However, disasters such as the current pandemic may require rapid, autarkic oxygen produc- tion. Therefore, we determined whether oxygen resilience could conceivably be improved through self-made oxygen generators using material that is easily available even in remote areas. The team comprised engineers and physicians with hands-on experience in low- and middle- income countries. We constructed and tested self-made setups for water hydrolysis and mem- brane-based oxygen purification. We must conclude, however, that the massive amounts of oxygen patients with COVID-19 require cannot be reasonably met with such simple measures, which would require high efforts and hold potential risk

Bed Rest, Exercise Countermeasure and Reconditioning Effects on the Human Resting Muscle Tone System

The human resting muscle tone (HRMT) system provides structural and functional support to skeletal muscle and associated myofascial structures (tendons, fascia) in normal life. Little information is available on changes to the HRMT in bed rest. A set of dynamic oscillation mechanosignals ([Hz], [N/m], log decrement, [ms]) collected and computed by a hand-held digital palpation device (MyotonPRO) were used to study changes in tone and in key biomechanical and viscoelastic properties in global and postural skeletal muscle tendons and fascia from a non-exercise control (CTR) and an exercise (JUMP) group performing reactive jumps on a customized sledge system during a 60 days head-down tilt bed rest (RSL Study 2015–2016). A set of baseline and differential natural oscillation signal patterns were identified as key determinants in resting muscle and myofascial structures from back, thigh, calf, patellar and Achilles tendon, and plantar fascia. The greatest changes were found in thigh and calf muscle and tendon, with little change in the shoulder muscles. Functional tests (one leg jumps, electromyography) showed only trends in relevant leg muscle groups. Increased anti-Collagen-I immunoreactivity found in CTR soleus biopsy cryosections was absent from JUMP. Results allow for a muscle health status definition after chronic disuse in bed rest without and with countermeasure, and following reconditioning. Findings improve our understanding of structural and functional responses of the HRMT to disuse and exercise, may help to guide treatment in various clinical settings (e.g., muscle tone disorders, neuro-rehabilitation), and promote monitoring of muscle health and training status in personalized sport and space medicine

Immobility-associated thromboprotection is conserved across mammalian species from bear to human

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. Here we aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as most substantially reduced protein. HSP47 downregulation or ablation attenuated immune cell activation and NET formation, contributing to thromboprotection in bears, SCI patients and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE

Pulse Contour Methods to Estimate Cardiovascular Indices in Micro- And Hypergravity

Background: The importance of noninvasive health monitoring in space increased as a result of the long-duration missions on the International Space Station (ISS). In order to monitor changes in cardiovascular indices such as cardiac output (CO) and total peripheral resistance (TPR), many methods have been developed using signal processing and mathematical modeling techniques. However, their performance in various gravitational conditions has not been known. Methods: The present study compared 10 methods to estimate CO and TPR by processing peripheral arterial blood pressure signals recorded from 8 subjects in multiple gravity levels (1 G, 0 G, and 1.8 G) during parabolic fl ights. For reference data sets, CO and TPR were simultaneously obtained by an inert gas rebreathing technique. Root normalized mean square errors and Bland-Altman plots were used to evaluate the estimation methods. Results: The corrected impedance method achieved the lowest estimation errors (20.0% CO error and 23.5% TPR error) over the three gravity levels. In microgravity, mean arterial pressure was also demonstrated to be an indicator of CO (24.5% error). Discussion: The corrected impedance method achieved low estimation errors for a wide range of the gravity levels. Gravity-dependent performance was observed in the mean arterial pressure method that achieved low errors in the shortterm 0 G

Petechiae: Reproducible Pattern of Distribution and Increased Appearance After Bed Rest

Exposure to acceleration can cause petechial hemorrhages, called G measles. Petechiae usually start to develop between 5 and 9 G with a high interindividual variance. Centrifuge training delays the onset to higher G levels. One might expect onset at lower G levels after bed rest; however, there is no evidence in the literature. A case of petechiae formation after bed rest is presented here. Case report: Orthostatic tolerance was tested using a tilt table and lower body negative pressure before and after bed rest in both campaigns of a 2 3 21-d bed rest study with 6° head-down tilt. A 42-yr-old male Caucasian without any history of thrombosis, venous disease, hemorrhage, or petechiae, and with a negative thrombophilia screening, took part in the bed rest study as 1 out of 10 subjects. He was the only one to develop petechiae during the orthostatic tests after, but not before, bed rest in both campaigns. Petechiae were distributed throughout the lower legs and most pronounced at the shin in a stocking-like fashion, surprisingly reoccurring in an identical pattern of distribution. Petechiae appeared slowly over minutes during hyperemia. Discussion: This case indicates that prolonged bed rest decreases the threshold for petechiae formation. A reproducible distribution pattern suggests that factors predisposing to petechiae formation keep their local distribution over time (possibly due to local vessel structures). Mechanisms of adaptation and interindividual variance are unclear. Findings are of clinical relevance as such cases might occur after prolonged bed rest in patients without need of expensive testing

Einführung von medizinischen Checklisten während einer Langzeit-Bettruhestudie erhöhen die Probandensicherheit und die Qualität der wissenschaftlichen Daten

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

Cardiopulmonary and Circulatory Interactions During Gravity Trasnsitions in Parabolic Flight - Joint Approach of Gravitational Physiology and Anaesthesiology -

Im Rahmen dieser Doktorarbeit wurden Parameter des Herzkreislaufsystems gesunder Probanden aus verschiedenen Biosignalen berechnet. Die Messungen wurden in den Schwerkraftsübergängen von Parabelflügen durchgeführt, während sich das Herzkreislaufsystem in keinem Gleichgewichtszustand befand. Außerdem wurden Interaktionen von kardiopulmonalem und hormonellem System und der Flüssigkeitshomöostase im Parabelflug untersucht. Kapitel eins gibt eine detaillierte Einleitung in die Gravitationsphysiologie und in die Herzkreislaufphysiologie auf Parabelflügen. Wissenschaftliche Überschneidungen von Physiologie unter extremen Umweltbedingungen und Anästhesiologie werden anhand klinischer und physiologischer Literatur aufgezeigt. Die wissenschaftlichen Methoden und Versuchseinrichtungen, die dieser Doktorarbeit zugrunde liegen, werden im Detail beschrieben. Kapitel zwei beschreibt das erste Experiment dieser Doktorarbeit im Rahmen dessen das Herzzeitvolumen kontinuierlich mittels Thoraximpedanzmethode und Fingerblutdruckanalyse auf Parabelflügen untersucht und mit dem nichtinvasiven Goldstandard der absoluten Herzzeitvolumenbestimmung, der Testgasrückatmung, verglichen wurde. Die Vergleichbarkeit der Methoden wurde mittels Bland und Altman Analyse bestimmt. Das absolute Herzzeitvolumen der stehenden Probanden wurde zum ersten Mal mittels der Rückatemmethode während des Übergangs von Hypergravitation in Mikrogravitation bestimmt. Kapitel drei beschreibt den Vergleich der Berechnung des Herzzeitvolumens auf der Grundlage von zehn verschiedenen Pulskontourmethoden während Schwerkraftsübergängen. Das Herzzeitvolumen der verschiedenen Pulskontourmethoden wurde mit dem gleichzeitig mittels Testgasrückatmung bestimmten Herzzeitvolumen verglichen. Kapitel vier stellt das abschließende physiologische Experiment der Arbeit dar, welches auf den Resultaten der Kapitel zwei und drei basiert. Dieses hatte die detaillierte Untersuchung des menschlichen Herzkreislaufsystems während Schwerkraftsübergängen im Parabelflug zum Ziel. Besonderes Gewicht wurde dabei auf die hormonelle Regulation des Wasserhaushalts und auf die Lungenzirkulation gelegt. Die Auswirkungen des verminderten Luftdrucks und des verminderten Sauerstoffpartialdrucks der Flugzeugkabine wurden berücksichtigt. Im fünften Kapitel werden die Ergebnisse dieser Arbeit in den klinischen und physiologischen Kontext eingeordnet. Dabei wird klar, dass die Pulskontourmethoden und die impedanzkardiographischen Methoden der kardiovaskulären Indexberechnung ähnliche methodische Limitationen in der Weltraummedizin wie auf einer Intensivstation haben. Außerdem wird klar, dass das Herzzeitvolumen in der Mikrogravitation eines Parabelflugs höher ist, als in dieser Situation vom Körper benötigt und dass die Lungenzirkulation und die Flüssigkeitshomöostase verschachtelten Regulationsmechanismen unterliegen, die von einer Vielzahl der Umweltfaktoren eines Parabelflugs beeinflusst werden

Psychogenic urinary retention associated with head down tilt bed rest: A rare medical complication

INTRODUCTION We describe a case of recurrent urinary retention (UR) during 12 degree head down tilt (12° HDT) bed rest during the 2-campaign Space-COT study. CASE A 47 yr. healthy ♂ subject with no previous urological conditions developed recurrent, UR during 12° HDT. The first episode occurred 3 h after transition from upright to HDT. A bladder ultrasound scan confirmed a highly distended bladder. The subject was given further time to void but developed lower abdominal pain, and was still unable to void. A disposable straight catheterization was performed to empty the bladder, which returned > 1000 ml of urine with immediate relief of discomfort. During the next urinary collection, the subject was again not able to urinate in HDT position. Thus the decision was made to place an indwelling urinary catheter (Fig. 2). The catheter was placed uneventfully, but had to be removed the following night on request of the subject due to persistent urethral discomfort. On the following day, it was decided by the medical team to allow temporary interruption of the 12° HDT angle to facilitate urination. At 10° head up tilt (HUT) the subject easily urinated. Using this procedure, the subject had no further issues of urinary retention during the first campaign. In preparation for campaign 2, one week later, the subject was given a large 12° wedge (Fig. 1) and urinary bottles to practice micturition at home. He reported no voiding disturbances in HDT position at home. During campaign 2, the UR immediately reappeared during HDT, and resolved with body angle change to supine position. DISCUSSION UR has been reported for spaceflight [1, 2] but not for HDT bedrest. Given in our case that UR appeared only during 12° HDT during the study, but not in the same position at home suggests that situational anxiety played a role. Alternatively, it is possible that the subject had an undiagnosed urological condition that may have contributed to urinary dysfunction, along with psychological stress; however, no previous urological symptoms had ever been reported. CONCLUSION UR, particularly during 12° HDT bed rest, can compromise study success but may be excludable in advance by testing the 12° HDT urination procedure during the medical selection process of the subjects