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Lee, Stuart M. C.

Publications and source records attributed to Lee, Stuart M. C..

At least 19 records

Submacular Choroid Thickness Increases During Long-Duration Spaceflight

The Spaceflight Associated Neuro-ocular Syndrome (SANS) is characterized by the development of optic disc edema, choroidal folds, cotton-wool spots, globe flattening, and/or refractive error changes greater than or equal to 0.75D during long-duration spaceflight to the International Space Station (ISS). It is hypothesized that these findings result from the headward fluid shift that occurs due to weightlessness. We can induce a headward fluid shift on Earth using positional changes and on ISS due to weightlessness. Lower-body negative pressure (LBNP) is used to reverse the headward fluid shift by drawing fluid into the lower body and can be used on Earth and on ISS.

Laurie, Steven S.↗

Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight.

Portable Pulmonary Function System (PPFS)↗

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified.

Portable Pulmonary Function System (PPFS)↗

Cardiovascular Disease Outcomes Among the NASA Astronaut Corps

BACKGROUND: 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 spaceflight activities are associated with changes in the cardiovascular system such as decreased carotid artery distensibility and decreased ventricular mass which may lead to an increased risk of cardiovascular disease. Additionally, astronauts who travel into space multiple times or for longer durations may be at an increased risk across their lifespan. To that end, the purpose of this study was to determine the incidence of common cardiovascular disease (CVD) outcomes among the NASA astronaut corps during their active career and through retirement. METHODS: Cardiovascular disease outcomes were defined as reports of any of the following: myocardial infarction (MI), revascularization procedures (coronary artery bypass graft surgery [CABG] or percutaneous coronary intervention [PCI]), hypertension, stroke or transient ischemic attack [TIA], heart failure, or total CVD (as defined by the AHA - combined outcome of MI, Angina Pectoris, heart failure, stroke, and hypertension). Each outcome was identified individually from review of NASA's Electronic Medical Record (EMR), EKG reports, and death certificates using ICD-9 codes as well as string searches of physician notes of astronaut exams that occurred between 1959 and 2016. RESULTS: Of 338 NASA astronauts selected as of 2016, 9 reported an MI, 12 reported a revascularization procedure, (7 PCI and 5 CABG), 4 reported Angina (without MI), 5 reported heart failure, 9 reported stroke/TIA, and 96 reported hypertension. Total CVD was reported in 105 astronauts. No astronaut who had an MI or revascularization procedure flew a spaceflight mission following the event. All MI, revascularization, and stroke events occurred in male astronauts. When reviewing astronaut ECG reports, abnormal ECG reports were found in only 8% of records (n=430) and mainly among retired astronauts (82%), with marked sinus bradycardia being the reason for the abnormal classification.

Charvat, Jacqueline M.↗

Using Concurrent Cardiovascular Information to Augment Survival Time Data for Evaluating Orthostatic Tilt Test Performance

Head-up tilt (HUT) tests often are used in research to measure orthostatic intolerance (OI) (inability to appropriately control blood pressure while upright) in clinical populations and otherwise healthy individuals after interventions. Post-space flight orthostatic intolerance is a well-known phenomenon, and countermeasures to its development has been an active area of research at NASA. In the NASA HUT protocol, subjects lie horizontally on an automatic tilt table for baseline measurements before being raised to 80deg head-up tilt for a defined period of time or until signs or symptoms of presyncope ensues (light-headedness, nausea, dizziness, sweating, weakness or fainting). Multiple measures are collected to evaluate the cardiovascular system's ability to respond appropriately to the orthostatic challenge. However if the intended duration of the HUT is short, the ability to detect changes in OI due to an intervention or its prevention by a countermeasure may be limited by a small number of failures to permit comparisons based on survival time alone. Thus, the time-trajectory of the cardiovascular data becomes an important additional source of information. In particular, we will show how various measures of trajectory variability can effectively augment survival analysis for the assessment of OI in a joint model when high censoring rates are present.

Feiveson, Alan H.↗

Risk of Cardiac Rhythm Problems During Spaceflight

NASA has concerns regarding the incidence and clinical significance of cardiac arrhythmias that could occur during long-term exposure to the spaceflight environment, such as on the International Space Station (ISS) or during a prolonged (e.g., up to 3 years) sojourn to Mars or on the Moon. There have been some anecdotal reports and a few documented cases of cardiac arrhythmias in space, including one documented episode of non-sustained ventricular tachycardia. The potential catastrophic nature of a sudden cardiac death in the remote space environment has led to concerns from the early days of the space program that spaceflight might be arrhythmogenic. Indeed, there are known and well-defined changes in the cardiovascular system with spaceflight: a) plasma volume is reduced, b) left ventricular mass is decreased, and c) the autonomic nervous system adapts to the weightless environment. Combined, these physiologic adaptations suggest that changes in cardiac structure and neuro-humoral environment during spaceflight could alter electrical conduction, although the evidence supporting this contention consists mostly of minor changes in QT interval (the time between the start of the Q wave and the end of the T wave on an electrocardiogram tracing) in a small number of astronauts after long-duration spaceflight. Concurrent with efforts by NASA Medical Operations to refine and improve screening techniques relevant to arrhythmias and cardiovascular disease, as NASA enters the era of exploration-class missions it will be critical to determine with the highest degree of certainty whether spaceflight by itself alters cardiac structure and function sufficiently to increase the risk of arrhythmias.

Lee, Stuart M. C.↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

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.↗

Effects of Long Duration Spaceflight on Venous and Arterial Compliance: Bed Rest

The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Ribeiro, L. Christine↗

Assessment of Intraocular and Systemic Vasculature Pressure Parameters in Simulated Microgravity with Thigh Cuff Countermeasure

Changes in vision have been well documented among astronauts during and after long-duration space flight. One hypothesis is that the space flight induced headward fluid alters posterior ocular pressure and volume and may contribute to visual acuity decrements. Therefore, we evaluated venoconstrictive thigh cuffs as a potential countermeasure to the headward fluid shift-induced effects on intraocular pressure (IOP) and cephalic vascular pressure and volumes.

Huang, Alex S.↗

Autonomous Diagnostic Imaging Performed by Untrained Operator Using Augmented Reality as a Form of "Just-in-Time" Training

We will address the Human Factors and Performance Team, "Risk of performance errors due to training deficiencies" by improving the JIT training materials for ultrasound and OCT imaging by providing advanced guidance in a detailed, timely, and user-friendly manner. Specifically, we will (1) develop an audio-visual tutorial using AR that guides non-experts through an abdominal trauma ultrasound protocol; (2) develop an audio-visual tutorial using AR to guide an untrained operator through the acquisition of OCT images; (3) evaluate the quality of abdominal ultrasound and OCT images acquired by untrained operators using AR guidance compared to images acquired using traditional JIT techniques (laptop-based training conducted before image acquisition); and (4) compare the time required to complete imaging studies using AR tutorials with images acquired using current JIT practices to identify areas for time efficiency improvements. Two groups of subjects will be recruited to participate in this study. Operator-subjects, without previous experience in ultrasound or OCT, will be asked to perform both procedures using either the JIT training with AR technology or the traditional JIT training via laptop. Images acquired by inexperienced operator-subjects will be scored by experts in that imaging modality for diagnostic and research quality; experts will be blinded to the form of JIT used to acquire the images. Operator-subjects also will be asked to submit feedback to improve the training modules used during the scans to improve future training modules. Scanned-subjects will be a small group individuals from whom all images will be acquired.

Martin, David S.↗

Defining the Relationship Between Biomarkers of Oxidation and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis.

Lee, Stuart M. C.↗

NASA'S Standard Measures During Bed Rest: Adaptations in the Cardiovascular System

Bed rest is a well-accepted analog of space flight that has been used extensively to investigate physiological adaptations in a larger number of subjects in a shorter amount of time than can be studied with space flight and without the confounding effects associated with normal mission operations. However, comparison across studies of different bed rest durations, between sexes, and between various countermeasure protocols have been hampered by dissimilarities in bed rest conditions, measurement protocols, and testing schedules. To address these concerns, NASA instituted standard bed rest conditions and standard measures for all physiological disciplines participating in studies conducted at the Flight Analogs Research Unit (FARU) at the University of Texas-Medical Branch. Investigators for individual studies employed their own targeted study protocols to address specific hypothesis-driven questions, but standard measures tests were conducted within these studies on a non-interference basis to maximize data availability while reducing the need to implement multiple bed rest studies to understand the effects of a specific countermeasure. When possible, bed rest standard measures protocols were similar to tests nominally used for medically-required measures or research protocols conducted before and after Space Shuttle and International Space Station missions. Specifically, bed rest standard measures for the cardiovascular system implemented before, during, and after bed rest at the FARU included plasma volume (carbon monoxide rebreathing), cardiac mass and function (2D, 3D and Doppler echocardiography), and orthostatic tolerance testing (15- or 30-minutes of 80 degree head-up tilt). Results to-date indicate that when countermeasures are not employed, plasma volume decreases and the incidence of presyncope during head-up tilt is more frequent even after short-duration bed rest while reductions in cardiac function and mass are progressive as bed rest duration increases. Additionally, while plasma volume loss can be corrected and cardiac mass can be prevented with properly applied countermeasures, orthostatic tolerance is more difficult to protect when supine exercise is the only countermeasure. Similar results have been observed after space flight. Plasma volume, cardiac chamber volume, and orthostatic tolerance recover relatively quickly with resumption of ambulation and normal activity levels after bed rest but restoration of cardiac mass is prolonged.

Lee, Stuart M. C.↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2pk)

Maximal oxygen (VO2pk) is the maximum amount of oxygen that the body can use during intense exercise and is used for benchmarking endurance exercise capacity. The most accurate method to determineVO2pk requires continuous measurements of ventilation and gas exchange during an exercise test to maximal effort, which necessitates expensive equipment, a trained staff, and time to set-up the equipment. For astronauts, accurate VO2pk measures are important to assess mission critical task performance capabilities and to prescribe exercise intensities to optimize performance. Currently, astronauts perform submaximal exercise tests during flight to predict VO2pk; however, while submaximal VO2pk prediction equations provide reliable estimates of mean VO2pk for populations, they can be unacceptably inaccurate for a given individual. The error in current predictions and logistical limitations of measuring VO2pk, particularly during spaceflight, highlights the need for improved estimation methods.

Downs, Meghan E.↗