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.

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal.

Importance: Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. Objective: To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. Design, Setting, and Participants: In the National Aeronautics and Space Administration's "Fluid Shifts Study," a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Interventions or Exposures: Spaceflight and lower-body negative pressure. Main Outcomes and Measures: Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Results: Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 µm; 95% CI, 27.9-39.7 µm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (-9.0 µm; 95% CI, -15.7 to -2.2 µm; P = .009), and decrease in macular thickness (fovea to 500 µm, 5.1 µm; 95% CI, 3.5-6.8 µm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Conclusions and Relevance: Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

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.

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.

Changes in the Optic Nerve Head and Choroid Over 1 Year of Spaceflight.

IMPORTANCE: While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. OBJECTIVE: To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. DESIGN, SETTING, AND PARTICIPANTS: The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year-long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. EXPOSURES: Crew members were tested before, during, and up to 1 year after spaceflight. MAIN OUTCOMES AND MEASURES: This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. RESULTS: Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] µm at flight day 270; participant 2, 539 [+56 from preflight] µm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] µm at flight day 90; participant 2, 528 [+45 from preflight] µm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. CONCLUSIONS AND RELEVANCE: This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted.

Automated MRI-based quantification of posterior ocular globe flattening and recovery after long-duration spaceflight.

BACKGROUND/OBJECTIVES: Spaceflight associated neuro-ocular syndrome (SANS), a health risk related to long-duration spaceflight, is hypothesized to result from a headward fluid shift that occurs with the loss of hydrostatic pressure gradients in weightlessness. Shifts in the vascular and cerebrospinal fluid compartments alter the mechanical forces at the posterior eye and lead to flattening of the posterior ocular globe. The goal of the present study was to develop a method to quantify globe flattening observed by magnetic resonance imaging after spaceflight. SUBJECTS/METHODS: Volumetric displacement of the posterior globe was quantified in 10 astronauts at 5 time points after spaceflight missions of ~6 months. RESULTS: Mean globe volumetric displacement was 9.88 mm3 (95% CI 4.56-15.19 mm3, p < 0.001) on the first day of assessment after the mission (R[return]+ 1 day); 9.00 mm3 (95% CI 3.73-14.27 mm3, p = 0.001) at R + 30 days; 6.53 mm3 (95% CI 1.24-11.83 mm3, p < 0.05) at R + 90 days; 4.45 mm3 (95% CI -0.96 to 9.86 mm3, p = 0.12) at R + 180 days; and 7.21 mm3 (95% CI 1.82-12.60 mm3, p < 0.01) at R + 360 days. CONCLUSIONS: There was a consistent inward displacement of the globe at the optic nerve, which had only partially resolved 1 year after landing. More pronounced globe flattening has been observed in previous studies of astronauts; however, those observations lacked quantitative measures and were subjective in nature. The novel automated method described here allows for detailed quantification of structural changes in the posterior globe that may lead to an improved understanding of SANS.

Quantitative magnetic resonance image assessment of the optic nerve and surrounding sheath after spaceflight.

A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery time points extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were -0.14 mm (95% CI: -0.36 to 0.08, Bonferroni-adjusted P = 1.00), 0.13 mm2 (95% CI -0.66 to 0.91, Bonferroni-adjusted P = 1.00), and -0.22 mm2 (95% CI: -1.78 to 1.34, Bonferroni-adjusted P = 1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.

In vivo estimation of optic nerve sheath stiffness using noninvasive MRI measurements and finite element modeling.

The optic nerve sheath (ONS) is biomechanically important. It is acted on by tension due to ocular movements, and by fluid shifts and/or alterations in intracranial pressure (ICP) in human disease, specifically in pathologies leading to intracranial hypertension. It has also been hypothesized that the ONS is acted on by altered ICP in astronauts exposed chronically to microgravity. However, a non-invasive method to quantify ONS biomechanical properties is not presently available; knowledge of such properties is desirable to allow characterization of the biomechanical forces exerted on the optic nerve head and other ocular structures due to the ONS. Thus, the primary objective of this study was to characterize the biomechanical properties (stiffness) of the human ONS in vivo as a necessary step towards investigating the role of ICP in various conditions, including Spaceflight Associated Neuro-ocular Syndrome (SANS). We acquired non-invasive magnetic resonance imaging (MRI) scans of ostensibly healthy subjects (n = 18, age = 30.4 ± 11.6 [mean ± SD] years) during supine and 15-degree head-down-tilt (HDT) postures, and extracted ONS contours from these scans. We then used finite element modeling to quantify ONS expansion due to postural changes and an inverse approach to estimate ONS stiffness. Using this non-invasive procedure, we estimated an in vivo ONS stiffness of 39.2 ± 21.9 kPa (mean ± SD), although a small subset of individuals had very stiff ONS that precluded accurate estimates of their stiffness values. ONS stiffness was not correlated with age and was higher in males than females.

Venous and Arterial Responses to Partial Gravity.

Introduction: Chronic exposure to the weightlessness-induced cephalad fluid shift is hypothesized to be a primary contributor to the development of spaceflight-associated neuro-ocular syndrome (SANS) and may be associated with an increased risk of venous thrombosis in the jugular vein. This study characterized the relationship between gravitational level (Gz-level) and acute vascular changes. Methods: Internal jugular vein (IJV) cross-sectional area, inferior vena cava (IVC) diameter, and common carotid artery (CCA) flow were measured using ultrasound in nine subjects (5F, 4M) while seated when exposed to 1.00-Gz, 0.75-Gz, 0.50-Gz, and 0.25-Gz during parabolic flight and while supine before flight (0-G analog). Additionally, IJV flow patterns were characterized. Results: IJV cross-sectional area progressively increased from 12 (95% CI: 9-16) mm2 during 1.00-Gz seated to 24 (13-35), 34 (21-46), 68 (40-97), and 103 (75-131) mm2 during 0.75-Gz, 0.50-Gz, and 0.25-Gz seated and 1.00-Gz supine, respectively. Also, IJV flow pattern shifted from the continuous forward flow observed during 1.00-Gz and 0.75-Gz seated to pulsatile flow during 0.50-Gz seated, 0.25-Gz seated, and 1.00-Gz supine. In contrast, we were unable to detect differences in IVC diameter measured during 1.00-G seated and any level of partial gravity or during 1.00-Gz supine. CCA blood flow during 1.00-G seated was significantly less than 0.75-Gz and 1.00-Gz supine but differences were not detected at partial gravity levels 0.50-Gz and 0.25-Gz. Conclusions: Acute exposure to decreasing Gz-levels is associated with an expansion of the IJV and flow patterns that become similar to those observed in supine subjects and in astronauts during spaceflight. These data suggest that Gz-levels greater than 0.50-Gz may be required to reduce the weightlessness-induced headward fluid shift that may contribute to the risks of SANS and venous thrombosis during spaceflight.

Efficacy of Gradient Compression Garments in the Hours After Long-Duration Spaceflight.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods: Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1-4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results: All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual's blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion: Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test.

Vestibular and Cardiovascular Responses After Long-Duration Spaceflight.

BACKGROUND: The vestibulo-sympathetic reflex operates during orthostatically challenging movements to initiate cardiovascular responses in advance of a baroreceptor-mediated response. The objective of this study was to determine whether there was an association between changes in vestibular function and cardiovascular responses during a prone-to-stand movement in astronauts after return from long-duration spaceflight.METHODS: Thirteen crewmembers who participated in International Space Station missions were tested before spaceflight and 1 d after landing. Vestibular function was evaluated by computerized dynamic posturography while their head was erect and while they performed dynamic head tilts. Heart rate and mean arterial blood pressure were measured while the subjects were in prone and standing positions.RESULTS: The 21.4% increase in the astronauts' heart rate during the prone to stand maneuver after spaceflight correlated significantly with their spaceflight-induced 48.7% decrease in postural stability during dynamic head tilts. The larger mean arterial pressure in the prone position after spaceflight compared to preflight (+7%) also correlated with the postflight decrease in postural stability during dynamic head tilts.CONCLUSION: These results indicate that an appropriate vestibular function is important to evoke optimum vestibulo-sympathetic response during orthostatically challenging voluntary movements performed after spaceflight. They also suggest that there may be a greater need to generate an anticipatory cardiovascular response after spaceflight.Deshpande N, Laurie SS, Lee SMC, Miller CA, Mulavara AP, Peters BT,Reschke MF, Stenger MB, Taylor LC, Wood SJ, Clément GR, Bloomberg JJ. Vestibular and cardiovascular responses after long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(8):621-627.

Arterial structure and function during and after long-duration spaceflight.

Spaceflight missions expose astronauts to increased risk of oxidative stress and inflammatory damage that might accelerate the development of asymptomatic cardiovascular disease. The purpose of this investigation was to determine whether long-duration spaceflight (>4 mo) results in structural and functional changes in the carotid and brachial arteries. Common carotid artery (CCA) intima-media thickness (cIMT), CCA distensibility and stiffness, and brachial artery endothelium-dependent and -independent vasodilation were measured in 13 astronauts (10 men, 3 women) ~180 and 60 days before launch, during the mission on ~15, 60, and 160 days of spaceflight, and within 1 wk after landing. Biomarkers of oxidative stress and inflammation were measured at corresponding times in fasting blood samples and urine samples from 24- or 48-h pools. Biomarkers of oxidative stress and inflammation increased during spaceflight, but most returned to preflight levels within 1 wk of landing. Mean cIMT, CCA stiffness, and distensibility were not significantly different from preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from preflight to postflight, but changes within individuals in endothelial function related to some biomarkers of oxidative stress. Whereas biomarkers of oxidative stress and inflammation are elevated during spaceflight, CCA and brachial artery structure and function were not changed by spaceflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and higher radiation exposure, may be problematic.NEW & NOTEWORTHY Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.

Association of Long-Duration Spaceflight With Anterior and Posterior Ocular Structure Changes in Astronauts and Their Recovery.

Importance: During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. Objective: To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). Design, Setting, and Participants: The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Main Outcomes and Measures: Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Results: Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 µm; 95% CI, 28.5-42.9 µm; P < .001; mean choroidal thickness change on flight day 150: 43 µm; 95% CI, 35-46 µm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). Conclusions and Relevance: This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

Intracranial Effects of Microgravity: A Prospective Longitudinal MRI Study.

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 µL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Unchanged cerebrovascular CO2 reactivity and hypercapnic ventilatory response during strict head-down tilt bed rest in a mild hypercapnic environment.

KEY POINTS: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts. We combined ∼4 mmHg ambient PCO2 with the strict head-down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one-half of the subjects. We demonstrate no change in arterialized PCO2 , cerebrovascular reactivity to CO2 or the hypercapnic ventilatory response. Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro-ocular syndrome. ABSTRACT: Chronically elevated carbon dioxide (CO2 ) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head-down tilt bed rest (HDTBR) in a mild hypercapnic environment ( PCO2 = ∼4 mmHg), we investigated arterialized PCO2 , cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized PCO2 was not significantly different from the pre-HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (-0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022-0.043; P < 0.001), which remained elevated by 0.021 (0.011-0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre-HDTBR levels 13 days after BR with a change of -0.001 (-0.009 to 0.007; P = 0.991). Compared to pre-HDTBR, cerebrovascular reactivity during and after HDTBR did not change. Baseline ventilation, ventilatory recruitment threshold and the slope of the ventilatory response were similar between pre-HDTBR and all other time points. Taken together, these data suggest that the mildly increased ambient PCO2 combined with 30 days of strict 6° HDTBR did not change arterialized PCO2 levels. Therefore, the experimental conditions were not sufficient to elicit a detectable physiological response.