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98 records · Page 6

Identification of Cardiometabolic Vulnerabilities Caused by Effects of Synergistic Stressors that are Commonly Encountered During Space Missions

Microgravity is a physiologically challenging state even when at rest. Astronauts experience additional physical and mental stresses, such as prolonged exertion, sleep loss and circadian misalignment, that could impact cardiovascular function. The main goals of this four year NASA project are to characterize the independent and synergistic effects on cardiovascular and immune function of: (1) circadian misalignment; (2) sleep loss; and (3) varied physical and mental stressors, mimicking some of the synergistic stressors experienced by astronauts. Sixteen healthy volunteers, aged 35-55 years, will be studied with standardized behavioral stressors occurring across all circadian phases, both with and without accruing sleep loss, achieved via two 11-day "forced desynchrony" protocols performed in each subject (randomized, within-subject design), where wake periods are advanced 4-h each "day" (i.e. recurring 20-h "days"). One protocol permits 8.33 h sleep opportunity per 20-h "day" (=10 h sleep per 24-h), and the other permits 5 h sleep per 20-h "day" (=6 h sleep per 24-h; matching the reported sleep duration of astronauts). In both protocols, subjects will perform a standardized stress battery including a cognitively challenging task; bicycle exercise, and passive 60deg head up tilt. Outcome variables include blood pressure, heart rate, arrhythmia frequency, cardiac vagal tone (from heart rate variability), sympathetic activity (catecholamines), and endothelial function. Additional measures of cardiac function (echocardiography), responses to a passive 80deg head up tilt, maximal oxygen uptake, and immune function will be assessed at the beginning and at the end of each protocol (i.e., without and with sleep loss, and before and after circadian misalignment). We hope to identify the relative impact on cardiovascular risk markers of varied behavioural stressors while subjects experience circadian misalignment and sleep loss, mimicking some of the synergistic stressors experienced by astronauts. Supported by NASANNX1 OAR 1 OG.

Ruger, M.↗

Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Charvat, Jacqueline M.↗

Preparation for an Earth Independent Medical Operations Demonstration using the Tempus ALS™ Medical Device

NASA’s exploration-class missions have severe resource constraints, long return trip durations, significant communication delays and limited resupply opportunities. Validation on the International Space Station (ISS) of medical devices that fit within Earth-Independent Medical Operations (EIMO) systems is a necessary preparation step. Key features of an EIMO medical system include: 1) technologies that support the prevention, diagnosis, and treatment of spaceflight medical events; 2) components that meet mass, volume, power and crew time/training constraints; 3) consideration of the medical skill level of the astronaut caregiver; 4) collection, storage and analysis of medical data within a central data architecture; and 5) incorporation of appropriate guidance and support tools that allow crew autonomy. The Human Research Program’s (HRP) Exploration Medical Capability (ExMC) Element and the Exploration Medical Integrated Product Team (XM-IPT) are planning an ISS technology demonstration to determine the feasibility of including a multifunctional medical device into an EIMO medical system. Demonstration Preparations: The Tempus ALS (Remote Diagnostic Technologies, Ltd., Philips Corp., Farnborough, UK) is a commercial-off-the-shelf medical device, with United States Food and Drug Administration clearance and is Conformité Européene marked in Europe. Several thousand units have been sold and are successfully operating in pre-hospital and in remote settings, such as by European Space Agency (ESA) flight surgeons and some of NASA’s commercial partners during post-flight medical operations. The Tempus ALS provides vital sign measurements such as blood pressure, electrocardiograms, heart rate, end tidal CO2, respiration rate, pulse oximetry and temperature. The device has ultrasound imaging and video laryngoscopy capabilities and has automatic or manual defibrillation modes for treating cardiac arrhythmias. It includes procedural guidance capabilities to assist in the collection of the vital sign measurements and it has various data transmission and report generation features. NASA’s HRP ExMC and XM-IPT are partnering with the ESA to demonstrate the Tempus ALS on ISS, with ESA manifesting the Tempus ALS and its accessories. ESA will compare performance of periodic health status exams and medical contingency drills performed nominally and with the Tempus ALS. NASA’s EIMO demonstration will include the use of Tempus ALS to diagnose a complaint of abdominal pain under increasingly independent circumstances. The caregiver must assess the present illness, collect vital sign measurements, and perform an abdominal ultrasound, under one of three communication situations, including real-time, with a several second delay and with a delay on the order of minutes. Expected Outcomes: Information will be gained about the feasibility, benefits, and challenges of using a multifunctional, all-in-one, medical device for medical diagnosis instead of separate devices with singular functionalities. Information will also be collected about performance differences as communication delays increase and available ground support decreases. Gaining this understanding will allow for further development of exploration medical system capabilities which takes the EIMO construct into consideration.

Beth Lewandowski↗

...And the Beats Keep Runnin Runnin (In Space)

Introduction: This case series describes the medical clearance of NASA astronauts after diagnosis of atrial fibrillation seeking to fly to the International Space Station (ISS). BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia with increasing incidence with age and is associated with increased lifetime risk of stroke. Treatment may consist of pharmacologic rate control and anticoagulation. Although it is not yet known how spaceflight modifies risk of cardioembolic event or adverse treatment effects, these can have significant impact on mission and crew health for spaceflight and granting a medical waiver for flight is a complex, case-by-case consideration. Case Presentation: We reviewed all records of waivers granted by NASA for atrial fibrillation and flutter, and identified 6 cases (4 short-duration [<18 days] and 2 long-duration missions [>60 days]) where waiver was granted with subsequent spaceflight. DISCUSSION: NASA has approved astronauts with a history of atrial fibrillation or flutter for flight following an appropriate medical evaluation. With the high prevalence of atrial fibrillation in the general population, we anticipate that consideration of medical waiver will become increasingly common as commercial spaceflight grows. These cases provide a potential framework for risk assessment and management of this population, to balance potential risk modification inherent in the microgravity environment against implications to crew performance, mission success, and personal health of spaceflight participants

Space Medicine↗

The Effects of Autogenic Feedback Training Exercise on Heart Rate Variability

INTRODUCTION: The development of Motion Sickness (MS) symptoms is correlated with increased sympathetic influence and irregular patterns of vagal activity. Such autonomic actions can be characterized by indices of heart rate variability (HRV), which reflect autonomic balance through neurocardiac function. Nonpharmacological interventions aimed at attenuating MS symptoms may therefore produce an effect on HRV. One such intervention that has been shown to mitigate MS symptoms is Autogenic Feedback Training Exercise (AFTE), which combines principles of autogenic therapy and biofeedback. AFTE teaches individuals to manipulate various physiological parameters in provocative environments and shows promise as a potential MS intervention in military aviators. The effects of AFTE on HRV have not previously been examined. Understanding HRV changes following AFTE may help to elucidate its indirect effects and inform its implementation for MS mitigation. METHODS: Twenty-four subjects received 2 hours of AFTE over 4 days. Pre- and post-AFTE rotating chair tests, which included stationary periods of baseline data, were conducted to evaluate the effects of AFTE. HRV data were recorded by SOMNOtouch™ NIBP. Post hoc analysis of pre- and post-AFTE short-term HRV (RMSSD, LF, HF, LF/HF) was performed. RESULTS: RMSSD, HF, and LF/HF were not significantly changed following AFTE. However, LF showed a statistically significant (p=0.015) decrease following AFTE. DISCUSSION: AFTE prescribes a respiratory rate of 15 breaths per minute (BPM), which is typically faster than participants’ pre-AFTE BPM (M=12.65). Healthy individuals can increase respiratory sinus arrhythmia (RSA) by slow, deep breathing. However, increasing the respiratory rate to 15 BPM may decrease RSA and subsequently HF. Increasing RSA potentially negates any influence of AFTE on HF, resulting in no significant change. RMSSD is correlated with HF power and was likewise not affected by AFTE. LF power, however, decreased significantly following AFTE, potentially indicating a lower sympathetic response in the post-AFTE measurement.

motion sickness↗

ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function

Cardiac pacemaker cells (PCs) in the sinoatrial node (SAN) have a distinct gene expression program that allows them to fire automatically and initiate the heartbeat. Although critical SAN transcription factors, including Isl1 (Islet-1), Tbx3 (T-box transcription factor 3), and Shox2 (short-stature homeobox protein 2), have been identified, the cis-regulatory architecture that governs PC-specific gene expression is not understood, and discrete enhancers required for gene regulation in the SAN have not been identified. Here, to define the epigenetic profile of PCs using comparative ATAC-seq (assay for transposase-accessible chromatin with sequencing) and to identify novel enhancers involved in SAN gene regulation, development, and function.

59 BASIC BIOLOGICAL SCIENCES↗

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients

Background: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. Methods: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. Results: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. Conclusion: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

60 APPLIED LIFE SCIENCES↗

Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome

A variety of approaches have been used to alleviate symptoms in postural tachycardia syndrome (POTS). Drugs reported to be of benefit include midodrine, propranolol, clonidine, and phenobarbital. Other measures used include volume expansion and physical countermaneuvers. These treatments may influence pathophysiologic mechanisms of POTS such as alpha-receptor dysfunction, beta-receptor supersensitivity, venous pooling, and brainstem center dysfunction. The authors prospectively studied hemodynamic indices and symptom scores in patients with POTS who were acutely treated with a variety of interventions. Twenty-one subjects who met the criteria for POTS were studied (20 women, 1 man; mean age, 28.7 +/- 6.8 y; age range, 14-39 y). Patients were studied with a 5-minute head-up tilt protocol, ECG monitoring, and noninvasive beat-to-beat blood pressure monitoring, all before and after the administration of an intervention (intravenous saline, midodrine, propranolol, clonidine, or phenobarbital). The hemodynamic indices studied were heart rate (ECG) and systolic, mean, and diastolic blood pressure. Patients used a balanced verbal scale to record any change in their symptoms between the tilts. Symptom scores improved significantly after the patients received midodrine and saline. Midodrine and propranolol reduced the resting heart rate response to tilt (p <0.005) and the immediate and 5-minute heart rate responses to tilt (p <0.002). Clonidine accentuated the immediate decrease in blood pressure on tilt up (p <0.05). It was concluded that midodrine and intravenous saline are effective in decreasing symptoms on tilt in patients with POTS when given acutely. Effects of treatments on heart rate and blood pressure responses generally reflected the known pharmacologic mechanisms of the agents.

Non-NASA Center↗