Self-Generated Lower Body Negative Pressure Exercise: A Low Power Countermeasure for Acute Space Missions.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Computational modelling of cardiovascular pathophysiology to risk stratify commercial spaceflight.

For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases. While data exist on the effects of gravitational and acceleration (G) forces on human physiology, data on the effects of the aerospace environment in unselected members of the public, and particularly in those with clinically significant pathology, are limited. Although short in duration, these high acceleration forces can potentially either impair the experience or, more seriously, pose a risk to health in some individuals. Rather than expose individuals with existing pathology to G forces to collect data, computational modelling might be useful to predict the nature and severity of cardiovascular diseases that are of sufficient risk to restrict access, require modification, or suggest further investigation or training before flight. In this Review, we explore state-of-the-art, zero-dimensional, compartmentalized models of human cardiovascular pathophysiology that can be used to simulate the effects of acceleration forces, homeostatic regulation and ventilation-perfusion matching, using data generated by long-arm centrifuge facilities of the US National Aeronautics and Space Administration and the European Space Agency to risk stratify individuals and help to improve safety in commercial suborbital spaceflight.

Jugular venous flow dynamics during acute weightlessness.

During spaceflight, fluids shift headward, causing internal jugular vein (IJV) distension and altered hemodynamics, including stasis and retrograde flow, that may increase the risk of thrombosis. This study's purpose was to determine the effects of acute exposure to weightlessness (0-G) on IJV dimensions and flow dynamics. We used two-dimensional (2-D) ultrasound to measure IJV cross-sectional area (CSA) and Doppler ultrasound to characterize venous blood flow patterns in the right and left IJV in 13 healthy participants (6 females) while 1) seated and supine on the ground, 2) supine during 0-G parabolic flight, and 3) supine during level flight (at 1-G). On Earth, in 1-G, moving from seated to supine posture increased CSA in both left (+62 [95% CI: +42 to 81] mm2, P < 0.0001) and right (+86 [95% CI: +58 to 113] mm2, P < 0.00012) IJV. Entry into 0-G further increased IJV CSA in both left (+27 [95% CI: +5 to 48] mm2, P = 0.02) and right (+30 [95% CI: +0.3 to 61] mm2, P = 0.02) relative to supine in 1-G. We observed stagnant flow in the left IJV of one participant during 0-G parabolic flight that remained during level flight but was not present during any imaging during preflight measures in the seated or supine postures; normal venous flow patterns were observed in the right IJV during all conditions in all participants. Alterations to cerebral outflow dynamics in the left IJV can occur during acute exposure to weightlessness and thus, may increase the risk of venous thrombosis during any duration of spaceflight.NEW & NOTEWORTHY The absence of hydrostatic pressure gradients in the vascular system and loss of tissue weight during weightlessness results in altered flow dynamics in the left internal jugular vein in some astronauts that may contribute to an increased risk of thromboembolism during spaceflight. Here, we report that the internal jugular veins distend bilaterally in healthy participants and that flow stasis can occur in the left internal jugular vein during acute weightlessness produced by parabolic flight.

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study.

OBJECTIVE: To determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort. METHODS: National Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index. RESULTS: There were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63). CONCLUSION: No increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.

Noninvasive indicators of intracranial pressure before, during, and after long-duration spaceflight.

Weightlessness induces a cephalad shift of blood and cerebrospinal fluid that may increase intracranial pressure (ICP) during spaceflight, whereas lower body negative pressure (LBNP) may provide an opportunity to caudally redistribute fluids and lower ICP. To investigate the effects of spaceflight and LBNP on noninvasive indicators of ICP (nICP), we studied 13 crewmembers before and after spaceflight in seated, supine, and 15° head-down tilt postures, and at ∼45 and ∼150 days of spaceflight with and without 25 mmHg LBNP. We used four techniques to quantify nICP: cerebral and cochlear fluid pressure (CCFP), otoacoustic emissions (OAE), ultrasound measures of optic nerve sheath diameter (ONSD), and ultrasound-based internal jugular vein pressure (IJVp). On flight day 45, two nICP measures were lower than preflight supine posture [CCFP: mean difference -98.5 -nL (CI: -190.8 to -6.1 -nL), P = 0.037]; [OAE: -19.7° (CI: -10.4° to -29.1°), P < 0.001], but not significantly different from preflight seated measures. Conversely, ONSD was not different than any preflight posture, whereas IJVp was significantly greater than preflight seated measures [14.3 mmHg (CI: 10.1 to 18.5 mmHg), P < 0.001], but not significantly different than preflight supine measures. During spaceflight, acute LBNP application did not cause a significant change in nICP indicators. These data suggest that during spaceflight, nICP is not elevated above values observed in the seated posture on Earth. Invasive measures would be needed to provide absolute ICP values and more precise indications of ICP change during various phases of spaceflight.NEW & NOTEWORTHY The current study provides new evidence that intracranial pressure (ICP), as assessed with noninvasive measures, may not be elevated during long-duration spaceflight. In addition, the acute use of lower body negative pressure did not significantly reduce indicators of ICP during weightlessness.

Bellagio II Report: Terrestrial Applications of Space Medicine Research.

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.

Optic disc edema and chorioretinal folds develop during strict 6° head-down tilt bed rest with or without artificial gravity.

Spaceflight associated neuro-ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head-down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two-thirds of the subjects received a daily 30-min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short-arm centrifugation to investigate whether this intervention would attenuate headward fluid shift-induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9-51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7-68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8-46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS.

Intraocular pressure and choroidal thickness respond differently to lower body negative pressure during spaceflight.

Spaceflight-associated neuro-ocular syndrome (SANS) develops during long-duration (>1 mo) spaceflight presumably because of chronic exposure to a headward fluid shift that occurs in weightlessness. We aimed to determine whether reversing this headward fluid shift with acute application of lower body negative pressure (LBNP) can influence outcome measures at the eye. Intraocular pressure (IOP) and subfoveal choroidal thickness were therefore evaluated by tonometry and optical coherence tomography (OCT), respectively, in 14 International Space Station crewmembers before flight in the seated, supine, and 15° head-down tilt (HDT) postures and during spaceflight, without and with application of 25 mmHg LBNP. IOP in the preflight seated posture was 14.4 mmHg (95% CI, 13.5-15.2 mmHg), and spaceflight elevated this value by 1.3 mmHg (95% CI, 0.7-1.8 mmHg, P < 0.001). Acute exposure to LBNP during spaceflight reduced IOP to 14.2 mmHg (95% CI, 13.4-15.0 mmHg), which was equivalent to that of the seated posture (P > 0.99), indicating that venous fluid redistribution by LBNP can influence ocular outcome variables during spaceflight. Choroidal thickness during spaceflight (374 µm, 95% CI, 325-423 µm) increased by 35 µm (95% CI, 25-45 µm, P < 0.001), compared with the preflight seated posture (339 µm, 95% CI, 289-388 µm). Acute use of LBNP during spaceflight did not affect choroidal thickness (381 µm, 95% CI, 331-430 µm, P = 0.99). The finding that transmission of reduced venous pressure by LBNP did not decrease choroidal thickness suggests that engorgement of this tissue during spaceflight may reflect changes that are secondary to the chronic cerebral venous congestion associated with spaceflight.NEW & NOTEWORTHY Spaceflight induces a chronic headward fluid shift that is believed to underlie ocular changes observed in astronauts. The present study demonstrates, for the first time, that reversing this headward fluid shift via application of lower body negative pressure (LBNP) during spaceflight may alter the ocular venous system, as evidenced by a decrease in intraocular pressure. This finding indicates that LBNP has the potential to be an effective countermeasure against the headward fluid shift during spaceflight, which may then be beneficial in preventing or reversing associated ocular changes.

Association of Structural Changes in the Brain and Retina After Long-Duration Spaceflight.

IMPORTANCE: Long-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments. OBJECTIVE: To determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020. EXPOSURES: Long-duration spaceflight (mean [SD], 191 [55] days). MAIN OUTCOMES AND MEASURES: Optical coherence tomography-derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging-derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume. RESULTS: In 19 healthy crew members included in this study (5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years), analyses revealed a positive, although not definitive, association between spaceflight-induced changes in total retinal thickness and lateral ventricle volume (4.7-µm increase in postflight total retinal thickness [95% CI, -1.5 to 10.8 µm; P = .13] per 1-mL postflight increase in lateral ventricle volume). Adjustments for mission duration improved the strength of association (5.1 µm; 95% CI, -0.4 to 10.5 µm; P = .07). No associations were detected between spaceflight-induced changes in total retinal thickness and white matter volume (0.02 µm; 95% CI, -0.5 to 0.5 µm; P = .94) or brain tissue plus cerebrospinal fluid volume, an estimate of intracranial volume (0.02 µm; 95% CI, -0.6 to 0.6 µm; P = .95). CONCLUSIONS AND RELEVANCE: These results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.

Mechanical countermeasures to headward fluid shifts.

Head-to-foot gravitationally induced hydrostatic pressure gradients in the upright posture on Earth are absent in weightlessness. This results in a relative headward fluid shift in the vascular and cerebrospinal fluid compartments and may underlie multiple physiological consequences of spaceflight, including the spaceflight-associated neuro-ocular syndrome. Here, we tested three mechanical countermeasures [lower body negative pressure (LBNP), venoconstrictive thigh cuffs (VTC), and impedance threshold device (ITD) resistive inspiratory breathing] individually and in combination to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog. Ten healthy subjects (5 male) underwent baseline measures (seated and supine postures) followed by countermeasure exposure in the supine posture. Noninvasive measurements included ultrasound [internal jugular veins (IJV) cross-sectional area, cardiac stroke volume, optic nerve sheath diameter, noninvasive IJV pressure], transient evoked otoacoustic emissions (OAE; intracranial pressure index), intraocular pressure, choroidal thickness from optical coherence tomography imaging, and brachial blood pressure. Compared with the supine posture, IJV area decreased 48% with application of LBNP [mean ratio: 0.52, 95% confidence interval (CI): 0.44-0.60, P < 0.001], 31% with VTC (mean ratio: 0.69, 95% CI: 0.55-0.87, P < 0.001), and 56% with ITD (mean ratio: 0.44, 95% CI: 0.12-1.70, P = 0.46), measured at end-inspiration. LBNP was the only individual countermeasure to decrease the OAE phase angle (Δ -12.9 degrees, 95% CI: -25 to -0.9, P = 0.027), and use of combined countermeasures did not result in greater effects. Thus, LBNP, and to a lesser extent VTC and ITD, represents promising headward fluid shift countermeasures but will require future testing in analog and spaceflight environments.NEW & NOTEWORTHY As a weightlessness-induced headward fluid shift is hypothesized to be a primary factor underlying several physiological consequences of spaceflight, countermeasures aimed at reversing the fluid shift will likely be crucial during exploration-class spaceflight missions. Here, we tested three mechanical countermeasures individually and in various combinations to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog.