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.

Early-phase musculoskeletal adaptations to different levels of eccentric resistance after 8 weeks of lower body training.

PURPOSE: Eccentric muscle actions are important to the development of muscle mass and strength and may affect bone mineral density (BMD). This study's purpose was to determine the relative effectiveness of five different eccentric:concentric load ratios to increase musculoskeletal parameters during early adaptations to resistance training. METHODS: Forty male subjects performed a supine leg press and calf press training program 3 days week(-1) for 8 weeks. Subjects were matched for pre-training leg press 1-repetition maximum strength (1-RM) and randomly assigned to one of five training groups. Concentric training load (% 1-RM) was constant across groups, but within groups, eccentric load was 0, 33, 66, 100, or 138% of concentric load. Muscle mass (dual energy X-ray absorptiometry; DXA), strength (1-RM), and BMD (DXA) were measured pre- and post-training. Markers of bone metabolism were assessed pre-, mid- and post-training. RESULTS: The increase in leg press 1-RM in the 138% group (20 ± 4%) was significantly greater (P < 0.05) than the 0% (8 ± 3%), 33% (8 ± 5%) and 66% (8 ± 4%) groups, but not the 100% group (13 ± 6 %; P = 0.15). All groups, except the 0% group, increased calf press 1-RM (P < 0.05). Leg lean mass and greater trochanter BMD were increased only in the 138% group (P < 0.05). CONCLUSIONS: Early-phase adaptations to eccentric overload training include increases in muscle mass and site-specific increases in BMD and muscle strength which are not present or are less with traditional and eccentric underload training. Eccentric overload provides a robust musculoskeletal stimulus that may benefit bedridden patients, individuals recovering from injury or illness, and astronauts during spaceflight.

Gradient compression garments protect against orthostatic intolerance during recovery from bed rest.

INTRODUCTION: Abdomen-high, lower body graded compression garments (GCGs) may represent the next-generation of orthostatic intolerance protection with applications for exploration missions and commercial space flight. PURPOSE: To evaluate the efficacy of the GCG to prevent orthostatic intolerance after a 14-day 6° head-down tilt bed rest (BR) and to determine whether wearing thigh-high compression garments impairs recovery from BR. METHODS: Sixteen (12 M, 4 F) subjects participated in a 15-min 80° head-up tilt test 5 day before BR (BR-5), on the last morning of BR (BR+0), and on day 1 (BR+1) and 3 after BR (BR+3). No subjects wore the GCG on BR-5, and all subjects wore the GCG during testing on BR+0. Control subjects (n = 8) wore the GCG only through testing on BR+0. Treatment subjects (n = 8) wore the GCG on BR+0 and thigh-high garments on BR+1 and BR+2. RESULTS: No subjects were presyncopal during tilt on BR+0 while wearing the GCG. Despite lower plasma volume index (BR-5: 1.52 ± 0.06, BR+0: 1.32 ± 0.05 l/m(2)), the tilt-induced increase in heart rate (ΔHR, 17 ± 2 bpm) and decrease in stroke volume (ΔSV, -28 ± 3 ml) on BR+0 were less than on BR-5 (24 ± 2 bpm, -43 ± 4 ml). On BR+1 ΔHR in the control group (33 ± 4 bpm) was higher than in the treatment group (23 ± 2 bpm) but there were no group differences on BR+3. CONCLUSIONS: Wearing the GCG prevented the orthostatic intolerance that is normally present after BR. Thigh-high garments provided protection after BR, and wearing these garments did not impair recovery.

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.

Sex differences in blood pressure control during 6° head-down tilt bed rest.

Spaceflight-induced orthostatic intolerance has been studied for decades. Although ∼22% of the astronaut corps are women, most mechanistic studies use mostly male subjects, despite known sex differences in autonomic control and postflight orthostatic intolerance. We studied adrenergic, baroreflex, and autonomic indexes during continuous infusions of vasoactive drugs in men and women during a 60-day head-down bed rest. Volunteers were tested before bed rest (20 men and 10 women) and around day 30 (20 men and 10 women) and day 60 (16 men and 8 women) of bed rest. Three increasing doses of phenylephrine (PE) and sodium nitroprusside were infused for 10 min after an infusion of normal saline. A 20-min rest period separated the phenylephrine and sodium nitroprusside infusions. Autonomic activity was approximated by spectral indexes of heart rate and blood pressure variability, and baroreflex sensitivity was measured by the spontaneous baroreflex slope. Parasympathetic modulation and baroreflex sensitivity decreased with bed rest, with women experiencing a larger decrease in baroreflex sensitivity by day 30 than men. The sympathetic activation of men and parasympathetic responsiveness of women in blood pressure control during physiological stress were preserved throughout bed rest. During PE infusions, women experienced saturation of the R-R interval at high frequency, whereas men did not, revealing a sex difference in the parabolic relationship between high-frequency R-R interval, a measurement of respiratory sinus arrhythmia, and R-R interval. These sex differences in blood pressure control during simulated microgravity reveal the need to study sex differences in long-duration spaceflight to ensure the health and safety of the entire astronaut corps.

Abdomen-high elastic gradient compression garments during post-spaceflight stand tests.

UNLABELLED: Space Shuttle astronauts wore an inflatable antigravity suit during reentry and landing, and astronauts and cosmonauts wear an elastic-compression garment (with lacing) during Soyuz re-entry and landings and in the first few days of recovery. However, neither garment is an ideal countermeasure to spaceflight-induced orthostatic intolerance. Our laboratory has been investigating an elastic graded compression garment (GCG) that applies graduated pressures from the feet to the abdomen for use following International Space Station missions and possibly during exploration missions. METHODS: Before and after Shuttle missions, 14 astronauts participated in a 3.5-min stand test. The stand test was conducted without garments preflight. On landing day, 7 astronauts wore the GCG while 7 astronauts did not (controls). Heart rate and blood pressure were measured in all astronauts during prone rest and standing. Stroke volume and cardiac output were measured only in GCG subjects. RESULTS: No astronauts in either group became presyncopal during the stand test preflight or postflight. The change in heart rate from prone to standing was lower in the GCG subjects on landing day than in the control subjects. Within the GCG subjects only, the increase in total peripheral resistance from prone to standing was higher after spaceflight. CONCLUSIONS: The GCG prevented tachycardia and increased total peripheral resistance with standing after spaceflight. The GCG shows promise as a countermeasure against post-spaceflight orthostatic intolerance, can be easily donned, and is relatively comfortable to wear, but has not been validated after long-duration spaceflight.

Artificial gravity training reduces bed rest-induced cardiovascular deconditioning.

We studied 15 men (8 treatment, 7 control) before and after 21 days of 6º head-down tilt to determine whether daily, 1-h exposures to 1.0 G(z) (at the heart) artificial gravity (AG) would prevent bed rest-induced cardiovascular deconditioning. Testing included echocardiographic analysis of cardiac function, plasma volume (PV), aerobic power (VO(2)pk) and cardiovascular and neuroendocrine responses to 80º head-up tilt (HUT). Data collected during HUT were ECG, stroke volume (SV), blood pressure (BP) and blood for catecholamines and vasoactive hormones. Heart rate (HR), cardiac output (CO), total peripheral resistance, and spectral power of BP and HR were calculated. Bed rest decreased PV, supine and HUT SV, and indices of cardiac function in both groups. Although PV was decreased in control and AG after bed rest, AG attenuated the decrease in orthostatic tolerance [pre- to post-bed rest change; control: -11.8 ± 2.0, AG: -6.0 ± 2.8 min (p = 0.012)] and VO(2)pk [pre- to post-bed rest change; control: -0.39 ± 0.11, AG: -0.17 ± 0.06 L/min (p = 0.041)]. AG prevented increases in pre-tilt levels of plasma renin activity [pre- to post-bed rest change; control: 1.53 ± 0.23, AG: -0.07 ± 0.34 ng/mL/h (p = 0.001)] and angiotensin II [pre- to post-bed rest change; control: 3.00 ± 1.04, AG: -0.63 ± 0.81 pg/mL (p = 0.009)] and increased HUT aldosterone [post-bed rest; control: 107 ± 30 pg/mL, AG: 229 ± 68 pg/mL (p = 0.045)] and norepinephrine [post-bed rest; control: 453 ± 107, AG: 732 ± 131 pg/mL (p = 0.003)]. We conclude that AG can mitigate some aspects of bed rest-induced cardiovascular deconditioning, including orthostatic intolerance and aerobic power. Mechanisms of improvement were not cardiac-mediated, but likely through improved sympathetic responsiveness to orthostatic stress.

Virtual guidance as a tool to obtain diagnostic ultrasound for spaceflight and remote environments.

INTRODUCTION: With missions planned to travel greater distances from Earth at ranges that make real-time two-way communication impractical, astronauts will be required to perform autonomous medical diagnostic procedures during future exploration missions. Virtual guidance is a form of just-in-time training developed to allow novice ultrasound operators to acquire diagnostically-adequate images of clinically relevant anatomical structures using a prerecorded audio/visual tutorial viewed in real-time. METHODS: Individuals without previous experience in ultrasound were recruited to perform carotid artery (N = 10) and ophthalmic (N = 9) ultrasound examinations using virtual guidance as their only training tool. In the carotid group, each untrained operator acquired two-dimensional, pulsed and color Doppler of the carotid artery. In the ophthalmic group, operators acquired representative images of the anterior chamber of the eye, retina, optic nerve, and nerve sheath. Ultrasound image quality was evaluated by independent imaging experts. RESULTS: Of the studies, 8 of the 10 carotid and 17 of 18 of the ophthalmic images (2 images collected per study) were judged to be diagnostically adequate. The quality of all but one of the ophthalmic images ranged from adequate to excellent. DISCUSSION: Diagnostically-adequate carotid and ophthalmic ultrasound examinations can be obtained by previously untrained operators with assistance from only an audio/video tutorial viewed in real time while scanning. This form of just-in-time training, which can be applied to other examinations, represents an opportunity to acquire important information for NASA flight surgeons and researchers when trained medical personnel are not available or when remote guidance is impractical.

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.

Near infrared spectroscopy-derived interstitial hydrogen ion concentration and tissue oxygen saturation during ambulation.

The objective of this study was to determine whether walking and running at different treadmill speeds resulted in different metabolic and cardiovascular responses in the vastus lateralis (VL) and lateral gastrocnemius (LG) by examining metabolite accumulation and tissue oxygen saturation. Ten healthy subjects (6 males, 4 females) completed a submaximal treadmill exercise test, beginning at 3.2 km h(-1) and increasing by 1.6 km h(-1) increments every 3 min until reaching 85% of age-predicted maximal heart rate. Muscle tissue oxygenation (SO(2)), total hemoglobin (HbT) and interstitial hydrogen ion concentration ([H(+)]) were calculated from near infrared spectra collected from VL and LG. The [H(+)] threshold for each muscle was determined using a simultaneous bilinear regression. Muscle and treadmill speed effects were analyzed using a linear mixed model analysis. Paired t-tests were used to test for differences between muscles in the [H(+)] threshold. SO(2) decreased (P = 0.001) during running in the VL and LG, but the SO(2) response across treadmill speeds was different between muscles (P = 0.047). In both muscles, HbT and [H(+)] increased as treadmill speed increased (P < 0.001), but the response to exercise was not different between muscles. The [H(+)] threshold occurred at a lower whole-body VO(2) in the LG (1.22 ± 0.63 L min(-1)) than in the VL (1.46 ± 0.58 L min(-1), P = 0.01). In conclusion, interstitial [H(+)] and SO(2) are aggregate measures of local metabolite production and the cardiovascular response. Inferred from simultaneous SO(2) and [H(+)] measures in the VL and LG muscles, muscle perfusion is well matched to VL and LG work during walking, but not running.

Test battery designed to quickly and safely assess diverse indices of neuromuscular function after unweighting.

Adequately describing the functional consequences of unweighting (e.g., bed rest, immobilization, spaceflight) requires assessing diverse indices of neuromuscular function (i.e., strength, power, endurance, central activation, force steadiness). Additionally, because unweighting increases the susceptibility of muscle to damage, testing should consider supplementary safety features. The purpose of this study was to develop a test battery for quickly assessing diverse indices of neuromuscular function. Commercially available exercise equipment was modified to include data acquisition hardware (e.g., force plates, position transducers) and auxiliary safety hardware (e.g., magnetic brakes). Ten healthy, ambulatory subjects (31 ± 5 years, 173 ± 11 cm, 73 ± 14 kg) completed a battery of lower- and upper-body neuromuscular function tests on 3 occasions separated by at least 48 hours. The battery consisted of the following tests, in order: (1) knee extension central activation, (2) knee extension force steadiness, (3) leg press maximal strength, (4) leg press maximal power, (5) leg press power endurance, (6) bench press maximal strength, (7) bench press force steadiness, (8) bench press maximal power, and (9) bench press power endurance. Central activation, strength, rate of force development, maximal power, and power endurance (total work) demonstrated good-to-excellent measurement reliability (SEM = 3-14%; intraclass correlation coefficient [ICC] = 0.87-0.99). The SEM of the force steadiness variables was 20-35% (ICC = 0.20-0.60). After familiarization, the test battery required 49 ± 6 minutes to complete. In conclusion, we successfully developed a test battery that could be used to quickly and reliably assess diverse indices of neuromuscular function. Because the test battery involves minimal eccentric muscle actions and impact forces, the potential for muscle injury has likely been reduced.

Metabolic consequences of garments worn to protect against post-spaceflight orthostatic intolerance.

INTRODUCTION: Astronauts have worn an inflatable antigravity suit (AGS) during Space Shuttle re-entry and landing to protect against hypotension and syncope, but ambulation with an inflated AGS requires significant effort and may prevent successful completion of an unaided emergency egress from the vehicle. NASA is considering the use of alternative garments to provide protection against post-spaceflight orthostatic intolerance. The purpose of this study was to compare the metabolic cost of walking in NASA's current AGS with that of walking in a commercially available elastic compression garment (thigh-high stockings), a candidate garment for use after exploration missions. METHODS: There were 10 volunteers (5 men, 5 women) who walked on a treadmill at 5.6 km x h(-1) for 5 min, a simulation of unaided egress previously used in our laboratory, in 3 different conditions presented in random order: wearing exercise clothes, wearing elastic compression garments, and wearing the AGS. Oxygen consumption (Vo2), carbon dioxide production (Vco2), and ventilation (V(E)) were compared using repeated-measures ANOVA and Tukey's Honestly Significant Difference test. RESULTS: Vo2 while wearing the AGS was 12% greater than when wearing the elastic compression garments and 15% greater than while wearing exercise clothes. There were no differences between the elastic compression garments and exercise clothes only conditions. Vco2 and VE also were greater while walking in the AGS than walking in the elastic compression garments or exercise clothes. CONCLUSIONS: Wearing elastic compression garments as a countermeasure to post-spaceflight orthostatic intolerance may not impair unaided egress from a space vehicle.

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.

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.