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.

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.

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.

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.

Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight.

Importance: Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. Objectives: To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. Design, Setting, and Participants: This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. Exposures: Posture changes on Earth, spaceflight, and lower body negative pressure. Main Outcomes and Measures: Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. Results: The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, -1.2 to 20.7) mm2 in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm2 during spaceflight (P < .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (P < .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. Conclusions and Relevance: This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

Cell wall teichoic acids of streptomycetes of the phenetic cluster 'Streptomyces fulvissimus'.

Structures of the anionic polymers of streptomycetes Streptomyces fulvissimus VKM Ac-994(T), Streptomyces longispororuber VKM Ac-1735(T), Streptomyces aureoveticillatus VKM Ac-48(T) and Streptomyces spectabilis INA 00606 belonging to the phenetic cluster 'S. fulvissimus' were investigated by chemical and NMR spectroscopic methods. A teichoic acid from the cell wall of S. spectabilis INA 00606 was studied in more detail, and this was shown to represent 1,3-poly(glycerol phosphate) substituted with glucosamine (alpha-D-GlcNAc) and L-glutamic acid (non-stoichiometric substitution). For the first time, glutamic acid is identified as an acyl substituent in teichoic acids of streptomycetes. The polymer chain is built of the following fragments: Cell walls of other streptomycetes of the phenocluster under study contain 1,3-poly(glycerol phosphates) with glucosamine as a glycosyl substituent at O-2 of the glycerol phosphate units and L-glutamic acid and lysine as O-2 acyl substituents. Not all amino sugar residues in the polymers of these strains are N-acetylated, and the content of the glucosamine and lysine residues in the polymers of different strains is not the same. Despite certain quantitative differences in the structures of the polymers, one may consider streptomycetes of the phenocluster 'S. fulvissimus' as closely related microorganisms, the details of the structures serving as additional criteria for the determination of the species status of a strain under study.

Cardiac and vascular responses to thigh cuffs and respiratory maneuvers on crewmembers of the International Space Station.

BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and under the influence of thigh occlusion cuffs available as a countermeasure device (Braslet cuffs). METHODS: Nine International Space Station crewmember subjects (expeditions 16-20) were examined in 15 experiment sessions 101 ± 46 days after launch (mean ± SD; 33-185). Twenty-seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs (162 parameter states/session). Quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by investigators from the NASA Telescience Center in Houston, TX, and the Mission Control Center in Korolyov, Moscow region, Russia. RESULTS: 14 of 81 conditions (27 parameters measured at baseline, Valsalva, and Mueller maneuver) were significantly different when the Braslet was applied. Seven of 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression. CONCLUSIONS: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient at the "microgravity bedside."