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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

A Gene Expression and Histologic Approach to Study Production and Outflow of Cerebrospinal Fluid in Hindlimb Suspended RATS

INTRODUCTION: The Spaceflight Associated Neuro-ocular Syndrome (SANS) is thought to be associated with weightlessness-induced cephalad fluid shift, possibly associated with a chronic elevation of intracranial pressure (ICP) during long-duration ISS missions. Changes in cerebrospinal fluid (CSF) dynamics and cranial compliance might be involved in the ICP increase. It is not known whether CSF production and/or outflow are altered in microgravity, but changes at the molecular and cellular level in the structures that produce and regulate the transcellular and paracellular secretion and reabsorption of CSF may be relevant. In this study, we used the rat hindlimb suspension (HS) model to examine the relationship between intracranial pressure (ICP) and the cellular responses to the prolonged change in body posture elicited specifically in the choroid plexus (CP). This was evaluated by transcriptomics, histopathology and ultrastructure of the CP and arachnoid villi (AV). METHODS: ICP was measured by telemetry. The morphology, ultrastructure, and gene expression profile of the CP was examined using male 9-month-old Long Evans rats subjected to HS for 14 and 90 days. A subset of animals completing 90-day HS returned to normal posture for 14 and 90 additional days of recovery. All HS rats had age-matched cage controls maintained in normal posture. A group of animals was maintained in conditions of 1% CO2 throughout the entire protocol. The rat brains were carefully removed and preserved for various analyses, including transmission electron microscopy (TEM), immunohistochemical analysis of specific targets involved in CSF regulation, and RNA sequencing analysis of laser capture micro-dissected CP tissue from the lateral ventricles. SUMMARY OF RESULTS: The ICP record was limited, which impacted any conclusions derived from the results. However, the ICP of rats in the CO2-enriched atmosphere appeared increased compared to those in a normal air composition. HS of rats resulted in an altered transcriptomics profile in the choroid plexus compared to animals maintained at normal posture. This was observed during both the HS period and during normal posture recovery period following 90 days of suspension. The greatest number of differentially expressed genes was observed at 90 days HS. Elevated CO2 also led to a different transcriptomics profile in the CP. The histology and ultrastructure results should be considered preliminary due to the limited number of samples. Examination of the CP by TEM showed blood vessel congestion and microvilli swelling in the CP, as well as some subpial and periventricular gliosis, but no associations were observed with treatment. There was no evidence of a reduced clearance of b-amyloid in the periventricular, perivascular and subpial regions of the brain in HS animals versus those in normal posture. Immunohistochemical staining of aquaporin 4, showed the localization to the subpial region and ependyma with increased immunoreactivity in the brains of CO2 exposed rats. This work was supported by awards NNX15AW48G to S.Z. Animal tissue and live data was provided under a tissue/data sharing agreement with Dr. Charles Fuller, UC Davis.

S B Zanello↗
NASA NTRSDate not supplied

Validation of Multisystem Countermeasures Protocol for Spaceflight during Antarctica Winter-over at Palmer Station (Palmer Countermeasures)

Exploration-class missions beyond the Van Allen belt to the Moon and then Mars will begin soon. Low-Earth orbital spaceflight results in the persistent perturbation of the human immune system, characterized by reductions in T and NK cell function, altered cytokine profiles, and the reactivation of latent herpesviruses. While these alterations have not caused widespread clinical issues, some crewmembers experience immune-related adverse events, including manifestations of symptomatic herpes viral reactivation, allergy, and respiratory distress. Because future deep-space exploration missions will be of unprecedented duration, it is reasonable to hypothesize that the immune perturbations observed aboard International Space Station (ISS) will intensify during longer missions in deep space, thereby placing crewmembers at elevated clinical risk. Thus, it is imperative to preserve the immune vigilance of astronauts by developing a countermeasure strategy. Of all the Earth analogs studied to date, an Antarctica winter-over (AWO) mission most closely reproduces the spaceflight experience: prolonged deployment, extreme environment, circadian misalignment, isolation, station lifestyle, and personal risk. The US maintains three primary stations in Antarctica: South Pole Station, McMurdo, and Palmer. Previous studies suggest that stations located near the interior of Antarctica (South Pole, McMurdo) have confounding effects on the immune system due to persistent hypobaric hypoxia. Thus, it was hypothesized that winter-over at a coastal station (Palmer) would be more akin to spaceflight due to its normoxic but still extreme environment. Therefore, AWO at Palmer Station was chosen as the platform for testing and validating the effectiveness of a NASA multi-system countermeasures protocol designed for deep space missions. The array of countermeasure protocols and monitoring methods deployed for each AWO will consist of diet modifications, nutritional supplementation, prescribed aerobic and resistive exercise, and a protocol of stress relieving virtual reality exercises. A multitude of biological sample types, including blood, saliva, and hair will be collected in tandem with the countermeasures in order to examine the combined effectiveness of the countermeasures. Samples and logs from subjects will be transported from Palmer Station to Johnson Space Center for further processing and distribution to co-investigators at the end of each winter-over. Extracted samples will be analyzed by appropriate testing platforms (Multiplex, qPCR, ELISA, etc.) to monitor alterations in leukocyte distribution, T cell and NK function, cytokine profiles, reactivation of latent herpesviruses, and nutritional factors. The data collected will be compared to a control year in which no countermeasures were deployed to evaluate the overall effectiveness of the analog and to validate the candidate immune countermeasure strategy. With the completion of the Antarctica Winter-Over (WO) 2022 control year, samples for 13 subjects have been successfully returned from Antarctica to NASA/JSC for further processing and distribution to Co-Investigators. WO 2023, the first countermeasure year, has also commenced with 11 subject consenting and performing their base line data collections (BDC) held in Chile. Another 5 subjects, who were already stationed at Palmer Station, Antarctica, joined as participates in the investigation. These 5 subjects were consented, but no BDC was able to be collected due to their joining in-mission. Therefore, there will be a total of 16 subjects participating in Antarctica's 2023 Winter-Over.

Cody L Gutierrez↗
NASA NTRS1992

Effects of inspired CO2, hyperventilation, and time on VA/Q inequality in the dog

In a recent study by Tsukimoto et al. (J. Appl. Physiol. 68: 2488-2493, 1990), CO2 inhalation appeared to reduce the size of the high ventilation-perfusion ratio (VA/Q) mode commonly observed in anesthetized mechanically air-ventilated dogs. In that study, large tidal volumes (VT) were used during CO2 inhalation to preserve normocapnia. To separate the influences of CO2 and high VT on the VA/Q distribution in the present study, we examined the effect of inspired CO2 on the high VA/Q mode using eight mechanically ventilated dogs (4 given CO2, 4 controls). The VA/Q distribution was measured first with normal VT and then with increased VT. In the CO2 group at high VT, data were collected before, during, and after CO2 inhalation. With normal VT, there was no difference in the size of the high VA/Q mode between groups [10.5 +/- 3.5% (SE) of ventilation in the CO2 group, 11.8 +/- 5.2% in the control group]. Unexpectedly, the size of the high VA/Q mode decreased similarly in both groups over time, independently of the inspired PCO2, at a rate similar to the fall in cardiac output over time. The reduction in the high VA/Q mode together with a simultaneous increase in alveolar dead space (estimated by the difference between inert gas dead space and Fowler dead space) suggests that poorly perfused high VA/Q areas became unperfused over time. A possible mechanism is that elevated alveolar pressure and decreased cardiac output eliminate blood flow from corner vessels in nondependent high VA/Q regions.

NASA Discipline Cardiopulmonary↗
NASA NTRS1989

Cardiovascular group

As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.

Blomqvist, Gunnar↗
NASA NTRS1994

Fluid Redistribution and Heart Rate in Humans During Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure

Gravity creates blood pressure gradients which redistribute body fluids towards the feet. Positive G(z) centrifugation and lower body negative pressure (LBNP) have been proposed to simulate these and other effects of gravity during long-term existence in microgravity. We hypothesized that the magnitude of upper-to-lower body fluid redistribution would increase according to the following order: short-arm centrifugation (SAC), long-arm centrifugation (LAC), head-up tilt (HUT), and LBNP. To test this hypothesis, we employed strain gauge plethysmography of the neck, thigh and calf during HUT and supine SAC and LAC up to lG(z) at the feet, and during supine LBNP to 100 mm Hg. Supine 100 mm Hg LBNP generates footward force and produces transmural blood pressures in the foot approximately equal to 1 G(z) (90 deg) HUT. Heart rate was measured via cardiotachometry. Control measurements were made while supine. SAC and LAC elicited similar increases in thigh volume at 1 G(z) (2.3 +/- 0.4 and 2.1 +/- 0.1%, respectively; mean +/- se, n greater than or equal to 7). At 100 mm Hg LBNP, thigh volume increased (3.4 +/- 0.3%) significantly more than during l G(z) centrifugation (p less than 0.05). Surprisingly, due to a paradoxical 0.6% reduction of thigh volume between 0.8 and 1.0 G(z) HUT, thigh volume was increased only 0.6 +/- 0.3% at 1 G(z) HUT. The calf demonstrated similar, although less definitive, responses to the various gravitational stimuli. Neck volume tended to decrease less during HUT than during the other stimuli. Heart rate increased similarly during HUT (18 +/- 2 beats/min) and LAC (12 +/- 2 beats/min), and exhibited still greater elevation during LBNP (29 +/- 4 beats/min), yet did not increase during SAC. These results suggest upright posture activates mechanisms that counteract footward fluid redistribution which are not activated during supine applications of simulated gravity. LAC more closely approximated effects of normal gravity (HUT) than LBNP. Therefore, when considering LBNP to simulate gravity, these findings support efforts to reduce the cardiovascular stress imposed by LBNP, while preserving the gravity-like force generated by LBNP.

Watenpaugh, D. E.↗
NASA NTRS2008

Exercise Increases the Cardiovascular Stimulus Provided by Artificial Gravity

We investigated fluid shifts and regulatory responses to variations of posture, exercise, Gz level and radius of rotation in subjects riding NASA Ames 20G centrifuge. Results are from 4 protocols that address radius and exercise effects only. Protocol A: After 10 min supine control, 12 healthy men (35 plus or minus 9 yr, 82.8 plus or minus 7.9 kg) were exposed to rotational 1 Gz (2.5 m radius) for 2 min followed by 20 min alternating between 1 and 1.25 Gz. Blood samples were taken pre and post spin. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 8.3 m. Protocol D: Same as B but at 8.3 m. The 8 subjects who completed all protocols, increased heart rate (HR) from control, on average, by: A: 5, B: 39, C: 11, D: 44 bpm. For thoracic fluid volume, (bioimpedance), the 8 subjects changed from control, on average: A: -394, B: -548, C: -537, D: -708 mL. For thigh fluid volume, changes from control, on average, were: A: -137, B: 129, C: -75, D: 159 mL. Hematocrit changes from control were: A: 2.3, B: 3.5, C: 2.3, D: 4.3 %. Radius effects were mild and included greater loss of fluid from the thorax, less fluid loss from the thigh and increased heart rate at the longer radius. Pre-acceleration exercise effects were more dramatic and included additional loss of fluid from the chest, increased fluid volume of the thigh, increased hematocrit and greater heart rate increases. We propose that short bouts of intense exercise can be used to magnify the cardiovascular stress delivered by artificial gravity (AG) training and the combination of AG with exercise training can be fine-tuned to preserve orthostatic tolerance of astronauts during spaceflight.

Howarth, M. S.↗
NASA NTRS2003

Excercise Within LBNP as an Artificial Gravity Countermeasure

Previous exercise in space has lacked sufficient loads to maintain preflight cardiovascular and musculoskeletal mass and function. Lower body negative pressure (LBNP) produces a static force equivalent to one Earth body weight by each 52 mm Hg of LBNP during supine posture. LBNP also provides transmural blood pressures simulating upright exercise. Thus, this artificial-gravity concept may help maintain cardiovascular and musculoskeletal systems of crewmembers during prolonged exposure to microgravity. Currently available, bungee cord assisted, treadmill exercise is limited by harness discomfort, lower than normal loads, abnormal post-flight gait, and the absence of gravitational blood pressures within the vascular system. PURPOSE: This project evaluates a method to create artificial gravity using supine LBNP treadmill exercise to prevent loss of physiologic function in microgravity simulated by 30 days of bed rest. Identical twins were used as volunteers so that statistical power could be maximized. This countermeasure is being transitioned to space flight. CURRENT STATUS OF RESEARCH Methods: Six sets of identical twins (6 females and 14 males, 21-36 years) remained in 6 head-down tilt (HDT) bed rest for 30 days to simulate prolonged microgravity. Six subjects were randomly selected to exercise supine in an LBNP chamber for 40 minutes six days per week (EX group), while their twin brothers served as non-exercise controls (CON). Pressure within the exercise LBNP chamber was adjusted to increase load, hence increasing exercise intensity. During supine treadmill exercise, LBNP (52-63 mmHg) was applied to produce foot ward forces equivalent to those for upright running on Earth at 1.0-1.2 times body weight (BW) and subjects performed an interval exercise protocol (40-80% peak exercise capacity [VO2pk]). Five minutes of resting LBNP immediately followed each exercise session. Results: Orthostatic tolerance time decreased significantly after 30 days bed rest in the CON group, but was relatively maintained in the EX group. VO2pk was maintained in EX males, but not in CON males. Isokinetic knee strength (extension, peak torque) decreased significantly in CON males, but was preserved in EX males. The EX group had significantly higher spine muscle strength after bed rest than the CON group. The cross-sectional area of spinal muscle at L4/5 level decreased significantly in the CON group but not in the EX group. Urinary n-telopeptide excretion, an index of bone resorption, was increased during bed rest in CON, but not in EX subjects. This suggests protection by LBNP exercise against the increase in bone resorption typically seen in simulated and actual microgravity. Significant changes in bone mineral density (BMD) in the spine and ribs were observed in CON subjects, but not in EX subjects. Conclusions: Our treadmill exercise protocol within LBNP plus a short period of post-exercise LBNP maintains orthostatic responses, upright exercise capacity and other important physiologic parameters during bed rest. These results document the efficacy of our apparatus and exercise protocol for maintaining physiologic structure and function during long-duration microgravity as simulated by 30 days of HDT bed rest. FUTURE PLANS: More sets of female identical twins are needed to reach significance. The LBNP exercise chamber will be redesigned for flight.

Hargens, A. R.↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight on Astronaut Health and Performance

INTRODUCTION Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis missions to the Moon and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices that provide both aerobic and resistive capabilities on one platform without including a treadmill. The European Enhanced Exploration Exercise Device [E4D] is one such apparatus. It is critical to validate the efficacy of using exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the effectiveness of using nominal ISS exercise devices for an entire mission compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS Crewmembers are assigned to one of three groups: 1) Controls (n ≥ 40), who partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), cycling on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS), and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who exercise on the CEVIS and ARED only (n = 8); and 3) Active Group 2, who perform aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both Active groups are not permitted to perform treadmill exercise for the entirety of their flight. Health and performance markers, including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and after spaceflight. RESULTS Fifteen subjects (4 Active [CEVIS + ARED], 11 Control) have been recruited. Data collection is ongoing. CONCLUSIONS This study will assess the efficacy of using exploration exercise modalities, including removing the treadmill exercise capability or exclusively using the E4D, compared to the nominal ISS exercise regimen across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions. Supported by the NASA Human Research Program and NASA Exploration Capabilities

A N Varanoske↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

Introduction: Current exercise countermeasures on the International Space Station (ISS), including treadmill running, cycle ergometry, and resistive exercise, are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices that provide both aerobic and resistive training on one platform without including a treadmill, such as the European Enhanced Exploration Exercise Device (E4D). It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. Methods: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40) who will partake in nominal exercise on the ISS, including running on the treadmill with vibration isolation system 2 (T2), ergometry on the cycle ergometer with vibration isolation and stabilization device (CEVIS), and strength training on the advanced resistive exercise device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. Results: Data collection for this study is currently in progress. Conclusions: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRS1996

Effects of Sustained Low-Level Elevations of Carbon Dioxide on Cerebral Blood Flow and Autoregulation of the Intracerebral Arteries in Humans

Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of 4 subjects using a 2 Mhz transcranial Doppler. Ambient CO2 was elevated to 0.7% for 23 days in the first study and to 1.2% for 23 days in the same subjects in the second study. By non-parametric testing CBFv was elevated significantly by +35% above pre-exposure levels during the first 1-3 days at both exposure levels after which CBFv progressively readjusted to pre-exposure levels. Despite similar CBFv responses, headache was only reported during the initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by rebreathing showed a similar pattern with the CBFv increases early in the exposures being greater than those elicited later. An increase in metabolic rate of the visual cortex was evoked by having the subjects open and close their eyes during a visual stimulus. Evoked CBFv responses measured in the posterior cerebral artery were also elevated in the first 1-3 days of both studies returning to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation assessed by raising head pressure during 10 deg head-down tilt both during the low-level exposures and during rebreathing was unaltered. There were no changes in the retinal microcirculation during serial fundoscopy studies. The time-dependent changes in CO2 vascular reactivity might be due either to retention of bicarbonate in brain extracellular fluid or to progressive increases in ventilation, or both. Cerebral vascular autoregulation appears preserved during chronic exposure to these levels of ambient CO2.

Sliwka, U.↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

INTRODUCTION: Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices (such as the European Enhanced Exploration Exercise Device [E4D]) that provide both aerobic and resistive training on one platform without including a treadmill. It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40), who will partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), ergometry on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) device, and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. RESULTS: Thirteen subjects (3 Active [CEVIS + ARED], 10 Control) have been recruited for this study. Data collection is currently in progress. CONCLUSIONS: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

INTRODUCTION: Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices (such as the European Enhanced Exploration Exercise Device [E4D]) that provide both aerobic and resistive training on one platform without including a treadmill. It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40), who will partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), ergometry on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) device, and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. RESULTS: Thirteen subjects (3 Active [CEVIS + ARED], 10 Control) have been recruited for this study. Data collection is currently in progress. CONCLUSIONS: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRSDate not supplied

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Critical mission tasks required by crews immediately after landing on a planetary surface include walking, jumping, and egressing from a seat. Understanding how these functional tasks are performed in partial gravity such as on the moon or Mars is necessary to define effective and comprehensive countermeasure strategies for preserving crew performance during exploration-class missions. We propose to study the performance of these tasks during the partial gravity phases of parabolic flight. These tasks will be performed using the same equipment and procedures as those used with astronauts returning from spaceflight and with ground-based subjects after prolonged axial body unloading during bed rest (sensorimotor standard measures). HYPOTHESIS We hypothesize that partial gravity during parabolic flight will cause acute changes in vestibular, proprioceptive, and sensorimotor functions, and these changes will impact the performance of mission critical tasks such as standing, walking, and jumping. The largest changes in performance are expected at the lowest gravity level (0.25g) because subjects will no longer be able to use the gravitational reference for the perception of upright. Ultimately, this information could be used to assess performance risks and inform the design of countermeasures for NASA exploration-class human missions. METHODS Twelve subjects will be tested during three flights of 30 parabolas, including 10 parabolas at 0.25g, 10 parabolas at 0.5g, and 10 parabolas at 0.75g. Subjects also will perform tests in 1g between parabolas. The tasks will be the same as those tested on astronauts returning from spaceflight: sit-to-stand with obstacle walk, tandem rail balance, jump down, and recovery from fall. Measurements will include: (a) time to test completion (sit-to-stand with obstacle walk, recovery from fall); (b) time elapsed between the start of motion and the stabilization of upright posture (recovery from fall, jump down); (c) mean sway speed during quiet standing (recovery from fall, jump down); (d) changes in heart rate and blood pressure (recovery from fall); (e) balance time and torso accelerations (tandem rail balance); (f) cone of stability (jump down); and (g) severity of motion sickness symptoms. RELEVANCE Although gravitational dose-response curves have been obtained for some biochemical systems in animals, these dose-responses are unknown for most human physiologic systems. Our study will compare the outcomes of four functional task tests in 0.25g, 0.5g, 0.75g, and 1g with those previously obtained in ground-based subjects after prolonged axial body unloading and in astronauts immediately after spaceflight. These comparisons will help us understand the true extent of functional task performance deficits in partial gravity. The dose-response relationship between gravity level and task performance decrement also will help determining the gravity threshold for these functional tasks. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element.

T. R. Macaulay↗
NASA NTRS2011

Nutrition Coupled with High-Load Traditional or Low-Load Blood Flow Restricted Exercise During Human Limb Suspension

High-load resistance exercise (HRE) and low-load blood flow restricted (BFR) exercise have demonstrated efficacy for attenuating unloading related muscle atrophy and dysfunction. In recreational exercisers, protein consumption immediately before and/or after exercise has been shown to increase the skeletal muscle anabolic response to resistance training. PURPOSE: To compare the skeletal muscle adaptations when chocolate milk intake was coupled with HRE or low-load BFR exercise [3 d/wk] during simulated lower limb weightlessness. METHODS: Eleven subjects were counterbalanced [based on age and gender] to HRE (31 +/- 14 yr, 170 +/- 13 cm, 71 +/- 18 kg, 2M/3W) or low-load BFR exercise (31 +/- 12 yr, 169 +/- 13 cm, 66 +/- 14 kg, 2M/4W) during 30 days of unilateral lower limb suspension (ULLS). Both HRE and BFR completed 3 sets of single leg press and calf raise exercise during ULLS. BFR exercise intensity was 20% of repetition maximum (1RM) with a cuff inflation pressure of 1.3 systolic blood pressure (143 4 mmHg). Cuff pressure was maintained during all 3 sets including rest intervals (90s). HRE intensity was 75% 1RM and was performed without cuff inflation. Immediately (<10 min) before and after exercise 8 fl oz of chocolate milk (150 kcal, 2.5g total fat, 22g total carbohydrate, 8g protein) was consumed to optimize acute exercise responses in favor of muscle anabolism. ULLS analog compliance was assessed from leg skin temperature recordings and plantar accelerometry. Muscle cross-sectional area (CSA) for knee extensor and plantar flexor muscle groups were determined from analysis of magnetic resonance images using ImageJ software. 1RM strength for leg press and calf raise was assessed on the Agaton exercise system. Muscular endurance during leg press and calf raise was evaluated from the maximal number of repetitions performed to volitional fatigue using 40% of pre-ULLS 1RM. RESULTS: Steps detected by plantar acceleometry declined by 98.9% during ULLS relative to an ambulatory control period. Average skin temperature of the unloaded calf declined from 27.4 C to 26.8 C (-2.1%), while there was a slight increase (+1.1%) in skin temperature in the loaded calf (27.6 C to 27.9 C). Collectively, these measures indicate strong subject compliance with the ULLS analog. Unloaded limb work performed during leg press (1514 +/- 334 vs. 576 +/- 103) and calf raise (2886 +/- 508 vs. 1233 +/- 153) exercises sessions was greater in HRE vs. BFR, respectively. Leg press training loads were 44 +/- 7 kg in HRE compared to 11 +/- 1 kg in BFR. Similarly, calf raise training loads were 81 +/- 11 kg in HRE and 16 +/- 1 kg in BFR. Pre to post-ULLS training adaptations in the unloaded leg are shown in the table. CONCLUSION: The preliminary results of this investigation suggest when HRE is optimized for muscle anabolism during unloading muscle size and strength are preserved (or enhanced) at the expense of muscle endurance. In contrast, when BFR exercise is optimized for muscle anabolism during unloading muscle endurance is preserved (or enhanced) at the expense of muscle size and strength

Hackney, K. J.↗
NASA NTRSDate not supplied

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Critical mission tasks that are required by crews immediately after landing on a planetary surface are seat egress, jump, and walk. To be able to define an effective and comprehensive countermeasure strategy for preserving crew performance during exploration-class missions, there is a need to understand how these functional tasks are actually performed in partial gravity such as on the Moon or Mars. We propose to study the performance in the execution of these tasks during the partial gravity and hypergravity phases of parabolic flight. These tasks will be completed using the same equipment and procedures as the Standard Measures Sensorimotor protocol, which is performed by astronauts returning from spaceflight and by ground-based subjects after prolonged axial body unloading during bed rest. HYPOTHESIS We hypothesize that partial gravity during parabolic flight will cause acute changes in vestibular, proprioceptive, and sensorimotor functions, and these changes will impact the performance of mission critical tasks such as standing, walking, and jumping. The largest changes in performance are expected at the lowest gravity level (0.25g) because subjects will no longer be able to use the gravitational reference for the perception of vertical. Ultimately, this information could be used to assess performance risks and inform the design of countermeasures for NASA exploration-class human missions. METHODS Twelve subjects will be tested during three flights of 30 parabolas, including 10 parabolas at 0.25g, 10 parabolas at 0.5g and 10 parabolas at 0.75g. Subject also will perform tests in 1g between parabolas and in hypergravity (1.8g) during the pull-out phases. Subjects will perform the same tasks as those tested on astronauts returning from spaceflight: sit-to-stand and obstacle walk, tandem walk, jump down, and recovery from fall. Measurements will include: (a) the time for the subject to complete the test (sit-to-stand and obstacle walk, recovery from fall); (b) the time elapsed between the start of motion and the stabilization of upright posture (recovery from fall, jump down); (c) the mean sway speed during quiet standing (recovery from fall, jump down); (d) changes in heart rate and blood pressure (recovery from fall); (e) the percentage of correct steps and torso acceleration (tandem walk); and (f) the severity of motion sickness symptoms. RELEVANCE Although gravitational dose-response curves have been obtained for some biochemical systems in animals, these dose-responses are unknown for most human physiologic systems. Our study will compare the outcomes of 5 functional task tests in 0.25g, 0.5g, 0.75g, 1g, and 1.8g with those previously obtained in ground-based subjects after prolonged axial body unloading and in astronauts immediately after spaceflight. This comparison will help understanding the true extent of functional task performance deficits in partial gravity. The dose-response relationship between gravity level and task performance decrement also will help determining the gravity threshold for these functional tasks. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element

Gilles Clement↗
NASA NTRS2025

Countermeasures for Mitigation of Sensorimotor Decrements Following Head-Down Tilt Bed Rest

BACKGROUND Astronauts experience postflight disturbances in postural and locomotor control due to sensorimotor adaptations during spaceflight. These alterations may have adverse consequences if a rapid egress is required after landing. Although exercise is partially effective for mitigating cardiovascular and muscular deconditioning, additional countermeasures are needed to further preserve sensorimotor function. Proprioception training and electrical muscle stimulation (EMS) are two promising in-flight countermeasures. Since prolonged head down tilt bed rest (HDTBR) is a spaceflight analog for body unloading and causes postural and locomotor control decrements that parallel those observed after spaceflight, it can be used to facilitate the development of these countermeasures. METHODS This study will determine the effects of proprioception training and EMS on functional task performance and sensorimotor function following 60 days of 6° HDTBR. Subjects will be randomly assigned to one of four groups: 1) an EMS arm, 2) a proprioception training arm, 3) an exercise plus proprioceptive training arm, and 4) a control arm. The EMS countermeasure will include daily bilateral stimulation of selected bilateral lower extremity muscles (30 minutes per session). Proprioception training will be performed three days per week (25 minutes per session) consisting of body-loaded postural tasks in the horizontal position on an air bearing sled. Exercise training will mimic current protocols used on the International Space Station, but treadmill aerobic exercise will be replaced with additional cycling aerobic exercise. Primary outcome measures will include pre- and post- HDTBR functional tests that require high demand for dynamic control of postural stability. Secondary measures will be used to explore key physiological changes that underlie countermeasure benefits. All HDTBR and data collection activities will be completed by the German Aerospace Center (DLR) at the :envihab facility. Given the constrained samples size, a Bayesian modelling approach will be used to quantify the probability that there is an effect of a given magnitude. HARDWARE AND PROTOCOL DEVELOPMENT Final hardware modifications and protocol developments were completed in preparation for Campaign 1, which began in September 2024. These included shipment, setup, and operator training for the transportable gravity bed, horizontal squat device, foam obstacle course, EMS devices, leg dexterity system, foot sole skin sensitivity system, and Radiofrequency Echographic Multi Spectrometry (REMS) ultrasound device. In addition, specialized protocols were developed for data collection using DLR’s equipment, including muscle morphology magnetic resonance imaging (MRI), optical coherence tomography, venous blood flow MRI and ultrasound, muscle ultrasound and impedance, and skin blood flow ultrasound. We will present early data from the first campaign, which concluded in November, 2024. These will be compared with previous data from the recent 30-day HDTBR campaigns (Spaceflight associated neuro-ocular syndrome countermeasures (SANS-CM)) conducted at DLR. RELEVANCE The deliverable from this project will be proof-of-concept sensorimotor countermeasure designs for functional task performance with full assessment of efficacy in a spaceflight analog. If one or more countermeasures are effective, they will be translated for validation with the suite of operationally implemented in-flight countermeasures.

T R Macaulay↗