ALBERT

Description: This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

Description: 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.

Description: 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.

Description: 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.

Description: Arterial health may be affected by microgravity or ground based analogs of spaceflight, as shown by an increase in thoracic aorta stiffness1. Head-down tilt bed rest (HDTBR) is often used as a ground-based simulation of spaceflight because it induces physiological changes similar to those that occur in space2, 3. This abstract details an analysis of arterial stiffness (a subclinical measure of atherosclerosis), the distensibility coefficient (DC), and the pressure-strain elastic modulus (PSE) of the arterial walls during HDTBR. This project may help determine how spaceflight differentially affects arterial function in the upper vs. lower body.

Description: Orthostatic Intolerance (OI) is the propensity to develop symptoms of fainting during upright standing. OI is associated with changes in heart rate, blood pressure and other measures of cardiac function. Problem: NASA astronauts have shown increased susceptibility to OI on return from space missions. Current methods for counteracting OI in astronauts include fluid loading and the use of compression garments. Multivariate trajectory spread is greater as OI increases. Pairwise comparisons at the same time within subjects allows incorporation of pass/fail outcomes. Path length, convex hull area, and covariance matrix determinant do well as statistics to summarize this spread Missing data problems Time series analysis need many more time points per OTT session treatment of trend? how incorporate survival information?

Description: No abstract available

Description: Future human space travel will primarily consist of long-duration missions aboard 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 primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Description: Orthostatic intolerance following spaceflight has been observed since the early days of manned spaceflight, and no countermeasure has been 100% effective. During re-entry NASA astronauts currently wear an inflatable anti-gravity suit (AGS) which compresses the legs and abdomen, but this device is uncomfortable and loses effectiveness upon egress from the Space Shuttle. We previously reported that foot-to-thigh, gradient compression stockings were comfortable and effective during standing after Shuttle missions. More recently we showed in a ground-based model of spaceflight that the addition of splanchnic compression to the foot-to-thigh compression stockings, creating foot-to-breast high compression, improved orthostatic tolerance in hypovolemic subjects to a level similar to the AGS. Purpose: To evaluate a new three-piece, foot-to-breast high gradient compression garment as a countermeasure to post-spaceflight orthostatic intolerance. Methods: Fourteen astronauts completed this experiment (7 control, 7 treatment) following Space Shuttle missions lasting 12-16 days. Treatment subjects were custom-fitted for a three-piece, foot-to-breast high compression garment consisting of shorts and foot-to-thigh stockings. The garments were constructed to provide 55 mmHg compression at the ankle and decreased gradually to 15 mmHg over the abdomen. Orthostatic testing occurred ~30 days before flight (without garments) and ~2 hours after flight (with garments for treatment group only) on landing day. Blood pressure (BP) and heart rate (HR) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stood. Data are reported as mean +/- SE. Results: The compression garment successfully prevented the tachycardia and hypotension typically seen post-spaceflight. On landing day, treatment subjects had a smaller change in HR (11+/-1 vs. 21+/-4 beats/min, p〈 or =0.05) and no decrease in systolic BP (2+/-4 vs. -9+/-2 mmHg, p〈 or =0.05). Garments also received good comfort ratings and were relatively easy to don. Conclusion: In this small group of astronauts, foot-to-breast high gradient compression garments seem to have prevented these negative effects of spaceflight on the cardiovascular responses to standing.

Description: 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.