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Macias, Brandon R.

Publications and source records attributed to Macias, Brandon R..

16 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Gravitational Influence on Intraocular Pressure: Implications for Spaceflight and Disease

Spaceflight-associated neuro-ocular syndrome (SANS) describes a series of morphologic and functional ocular changes in astronauts first reported by Mader and colleagues in 2011. SANS is currently clinically defined by the development of optic disc edema during prolonged exposure to the weightless (microgravity) environment, which currently occurs on International Space Station (ISS). However, as improvements in our understanding of the ocular changes emerge, the definition of SANS is expected to evolve. Other ocular SANS signs that arise during and after ISS missions include hyperopic shifts, globe flattening, choroidal/retinal folds, and cotton wool spots. Over the last 10 years, ~1 in 3 astronauts flying long-duration ISS missions have presented with ≥ 1 of these ocular findings. Commensurate with research that combines disparate specialties (vision biology and spaceflight medicine), lessons from SANS investigations may also yield insight into ground-based ocular disorders, such as glaucomatous optic neuropathy that may have the potential to lessen the burden of this irreversible cause of vision loss on Earth.

Episcleral venous pressure↗
NASA NTRS2018

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.↗
NASA NTRS2018

MRI-based Quantification of Optic Nerve Tortuosity and Subarachnoid Space 3D Geometry: Reliability Assessment

In some astronauts, long-duration space flight results in ophthalmic structure changes such as optic nerve (ON) kinking, ON distention, and globe flattening. Assessment of the ON and ON sheath (ONS) may provide insight into the mechanisms responsible for ophthalmic structure changes seen in a subset of astronauts. Automated and manual methods were developed to quantify 3D ON/ONS geometry and ON tortuosity.

Rohr, Jesse J.↗
NASA NTRS2017

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.↗
NASA NTRS2017

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.↗
NASA NTRS2017

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.↗
NASA NTRS2016

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.↗
NASA NTRS2016

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. 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. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗
NASA NTRS2006

WISE-2005: LBNP/Treadmill and Resistive Exercise Countermeasures Maintain Aerobic Capacity during a 60-d Bed Rest

We have previously documented that supine treadmill exercise within lower body negative pressure (LBNPex) performed 6 sessions (raised dot) wk(sup -1) during 15- and 30-day bed rests (BR) maintained upright aerobic capacity (VO2pk). In the present study, ure are evaluating whether aerobic capacity is maintained during a 60-d BR when the LBNPex frequency is reduced to 2-4 sessions (raised dot) wk(sup -1) and resistance exercise (REX) is added 2-3 sessions (raised dot) wk(sup -1). Eight healthy women (32 plus or minus 4 yrs; 56.4 plus or minus 3.6 kg; 164 plus or minus 8 cm; mean plus or minus SD) performed maximal-exertion, graded treadmill tests before and 3 days after a 60-d, 6 deg. head-down tilt BR. (Earliest day the medical monitors would permit a maximal exercise test post-BR). During BR, four subjects performed no exercise (CON), while four other subjects (EX) performed LBNPex and REX on separate days. The LBNPex countermeasure employed an intermittent (40-80% pre-BR VO2pk), 40-min protocol against an LBNP pressure (-49 plus or minus 3 mmHg) applied to provide a footward force equivalent to 1.0-1.2 body weight. REX consisted of maximal concentric and eccentric supine leg press and heel raise exercises using a gravity-independent flywheel ergometer. Comparisons were performed using paired (within-group) or non-paired (between-group) t-tests. Three days post-BR, VO2pk of the CON group was reduced significantly from pre-BR (Pre:37.2 plus or minus 1.2, Post: 29.4 plus or minus 2 ml (raised dot) kg(sup -1) (raised dot) min(sup -1), P less than 0.05), while the VO2pk of the EX group was not significantly reduced (Pre: 39.6 plus or minus 1.9, Post: 38.0 plus or minus 0.6 ml (raised dot) kg(sup -1) (raised dot) min(sup -1)). Peak heart rate, ventilation, rating of perceived exertion, and respiratory exchange ratio were not significantly different between the two groups pre- and post-BR. These preliminary results suggest that the combined LBNPex and REX countermeasures may be sufficient to maintain upright aerobic capacity after long-duration space flights.

Schneider, Suzanne M.↗
NASA NTRS2006

Supine Lower Body Negative Pressure Exercise Maintains Upright Exercise Capacity in Male Twins during 30 Days of Bed Rest

Exercise capacity is reduced following both short and long duration exposures to microgravity. We have shown previously that supine lower body negative pressure with exercise (LBNP(sub ex) maintains upright exercise capacity in men after 5d and 15d bed rest, as a simulation of microgravity. We hypothesized that LBNP(sub ex) would protect upright exercise capacity (VO2pk) and sprint performance in eight sets of identical male twins during a 30-d bed rest. Twins within each set were randomly assigned to either a control group (CON) who performed no exercise or to an exercise group (EX) who performed a 40-min interval (40-80% pre-BR VO2pk) LBNP(sub ex) (55+/-4 mmHg) exercise protocol, plus 5 min of resting LBNP, 6 d/wk. LBNP produced footward force equivalent to 1.0- 1.2 times body weight. Pre- and post-bed rest, subjects completed an upright graded exercise test to volitional fatigue and sprint test of 30.5 m. After bed rest, VO2pk was maintained in the EX subjects (-3+/-3%), but was significantly decreased in the CON subjects (-24+/-4%). Sprint time also was increased in the CON subjects (24+/-8%), but maintained in the EX group (8+/-2%). The performance of a supine, interval exercise protocol with LBNP maintains upright exercise capacity and sprint performance during 30 d of bed rest. This exercise countermeasure protocol may help prevent microgravity-induced deconditioning during long duration space flight.

Lee, Stuart M. C.↗
NASA NTRS2005

EXERCISE WITHIN LOWER BODY NEGATIVE PRESSURE AS AN ARTIFICIAL GRAVITY COUNTERMEASURE

Current exercise systems for space, which attempt to maintain performance, are unable to generate cardiovascular and musculoskeletal loads similar to those on Earth [1, 2]. The purpose of our research is to evaluate the use of lower body negative pressure (LBNP) treadmill exercise to prevent deconditioning during simulated microgravity.

Hargens, Alan R.↗
NASA NTRS2003

Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Twin Study↗
NASA NTRS2003

Cranial diameter pulsations measured by non-invasive ultrasound decrease with tilt

INTRODUCTION: Intracranial pressure (ICP) may play a significant role in physiological responses to microgravity by contributing to the nausea associated with microgravity exposure. However, effects of altered gravity on ICP in astronauts have not been investigated, primarily due to the invasiveness of currently available techniques. We have developed an ultrasonic device that monitors changes in cranial diameter pulsation non-invasively so that we can evaluate ICP dynamics in astronauts during spaceflight. This study was designed to demonstrate the feasibility of our ultrasound technique under the physiological condition in which ICP dynamics are changed due to altered gravitational force. METHODS: Six healthy volunteers were placed at 60 degrees head-up, 30 degrees headup, supine, and 15 degrees head-down positions for 3 min at each angle. We measured arterial blood pressure (ABP) with a finger pressure cuff, and cranial diameter pulsation with a pulsed phase lock loop device (PPLL). RESULTS: Analysis of covariance demonstrated that amplitudes of cranial diameter pulsations were significantly altered with the angle of tilt (p < 0.001). The 95% confidence interval for linear regression coefficients of the cranial diameter pulsation amplitudes with tilt angle was 0.862 to 0.968. However, ABP amplitudes did not show this relationship. DISCUSSION: Our noninvasive ultrasonic technique reveals that the amplitude of cranial diameter pulsation decreases as a function of tilt angle, suggesting that ICP pulsation follows the same relationship. It is demonstrated that the PPLL device has a sufficient sensitivity to detect changes non-invasively in ICP pulsation caused by altered gravity.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS2003

Pulsed Phase Lock Loop Device for Monitoring Intracranial Pressure During Space Flight

We have developed an ultrasonic device to monitor ICP waveforms non-invasively from cranial diameter oscillations using a NASA-developed pulsed phase lock loop (PPLL) technique. The purpose of this study was to attempt to validate the PPLL device for reliable recordings of ICP waveforms and analysis of ICP dynamics in vivo. METHODS: PPLL outputs were recorded in patients during invasive ICP monitoring at UCSD Medical Center (n=10). RESULTS: An averaged linear regression coefficient between ICP and PPLL waveform data during one cardiac cycle in all patients is 0.88 +/- 0.02 (mean +/- SE). Coherence function analysis indicated that ICP and PPLL waveforms have high correlation in the lst, 2nd, and 3rd harmonic waves associated with a cardiac cycle. CONCLUSIONS: PPLL outputs represent ICP waveforms in both frequency and time domains. PPLL technology enables in vivo evaluation of ICP dynamics non-invasively, and can acquire continuous ICP waveforms during spaceflight because of compactness and non-invasive nature.

Ueno, Toshiaki↗