Centrifuge-Simulated Spaceflight After Aortic Valve Replacement and Atrial Septal Defect Repair.

INTRODUCTION: Human access to space is expanding rapidly in the commercial environment, with various private companies offering commercial flights to spaceflight participants (SFPs). SFPs are more likely than career astronauts to have medical conditions novel to spaceflight and may not have undergone as rigorous a medical screening process as that used for career astronauts, representing new and unstudied risks in the spaceflight environment. We report participation of a subject with recent median sternotomy for aortic valve replacement and atrial septal defect closure in centrifuge-simulated dynamic phases of orbital and suborbital spaceflight.CASE REPORT: A 40-yr-old man with a history of congenital bicuspid aortic valve and atrial septal defect with successful repair 8 mo prior participated in an ongoing human centrifuge research study. The subject had the opportunity to participate in up to five centrifuge runs in an 8-h period, with profiles simulating commercial spaceflight. Maximum exposures included +4.0 Gz, +4.5 Gx, 6.1 G resultant, and maximum onset rate < 0.5 Gz · s-1 and +1 Gx · s-1. Physiological data acquisition included hemodynamics, electrocardiogram, neurovestibular exams, and postrun questionnaires covering motion sickness, disorientation, and similar. The subject tolerated the physiological aspects of hypergravity well, noting progressive sternal pain with increasing +Gx, ultimately leading him to opt out of the final profile.DISCUSSION: Postcardiothoracic surgery risks to SFPs are largely unknown, especially within 12 mo of a significant surgical procedure. This case provides an approach for risk stratification, preparticipation evaluation, and medical management of a postsurgical patient with significant cardiac history in spaceflight and analog environments.Fernandez WL, Blue RS, Harrison MF, Powers W, Shah R, Auñón-Chancellor S. Centrifuge-simulated spaceflight after aortic valve replacement and atrial septal defect repair. Aerosp Med Hum Perform. 2024; 95(2):123-131.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

Layperson Physiological Tolerance and Operational Performance in Centrifuge-Simulated Spaceflight.

INTRODUCTION: Prior study has indicated that individuals of varied age, medical history, and limited-to-no experience tolerate spaceflight conditions. We sought to expand upon the understanding of layperson response to hypergravity conditions expected in commercial spaceflight by exposing subjects, following minimal training, to centrifuge-simulated, high-fidelity commercial spaceflight profiles. We further explored how these individuals perform in simulated operational activities during and following hypergravity.METHODS: Volunteer subjects participated in up to five centrifuge runs (maximum +4.0 Gz, +4.5 Gx, 6.1 G resultant; onset rate <0.5 Gz · s-1, ≤1 Gx · s-1). Profiles included two winged spacecraft simulations with sequential and combined +Gx/+Gz and two capsule simulations representing nominal +Gx launch and reentry. The final profile simulated a capsule launch abort, with a more dynamic cycling of +Gx exposures and oscillatory multi-axis exposures simulating parachutes and water motion. Touchscreen tablets were used to administer pattern-replication tasks during and after profiles.RESULTS: A total of 46 subjects participated, including 4 diabetics and 9 with cardiac disease. There was increased frequency of motion sickness, subjectively associated with capsule-type profiles, and increased termination of participation compared to prior studies. There was no association between medical history, age, sex, or motion sickness history and tolerance or noncompletion. Tablet test errors were common; accuracy and time to completion were associated with age. There was no association between any time metric or accuracy and sex.DISCUSSION: This study improves understanding of layperson tolerance in commercial spaceflight analog conditions, and the capsular profiles broaden the applicability of the findings. The frequency of task errors highlights the potential for mistakes in operational activities when performed by laypersons.Blue RS, Ong KM, Ray K, Menon A, Mateus J, Auñón-Chancellor S, Shah R, Powers W. Layperson physiological tolerance and operational performance in centrifuge-simulated spaceflight. Aerosp Med Hum Perform. 2023; 94(8):584-595.

Tolerance of Centrifuge-Simulated Commercial Spaceflight in a Subject with Hemophilia A.

INTRODUCTION: With increasing engagement of commercial spaceflight participants in spaceflight activities, the evaluation of individuals with medical conditions not previously characterized in the spaceflight environment is of particular interest. Factors such as acceleration forces experienced during launch, reentry, and landing of spacecraft could pose an altered risk profile in some individuals due to known disease. Bleeding diatheses present a unique concern in the spaceflight environment given hypergravity exposure and, particularly, the potential for injury resulting from transient or impact acceleration.CASE REPORT: A 26-yr-old Caucasian man with severe hemophilia A and no detectable endogenous Factor VIII (FVIII) volunteered for participation in hypergravity exposures simulating spaceflight. His treatment regimen included 50 IU · kg-1 FVIII-Fc fusion protein intravenous administration every 96 h, with supplemental FVIII administration as needed for injury or bleeding. The subject experienced two profiles at the National Aerospace Training and Research Center (NASTAR), with maximum exposure +4.0 Gz, +4.5 Gx, 6.1 G resultant, and maximum onset rate <0.5 Gz · s-1 and +1 Gx · s-1. The subject reported no abnormal events during the profiles other than brief mild vertigo. No petechial hemorrhage, ecchymosis, or other bleeding was noted during or after profiles. Supplemental FVIII was not required before, during, or after exposure.DISCUSSION: Inherited bleeding disorders present several potential concerns that must be evaluated prior to spaceflight participation. Cautious review and management of medical history, adherence and barriers to treatment, duration of spaceflight and longitudinal management concerns, and a thorough and detailed risk/benefit assessment may provide a future pathway for inclusion of individuals with hematological disorders in commercial spaceflight.Reeves IA, Blue RS, Auñon-Chancellor S, Harrison MF, Shah R, Powers WE. Tolerance of centrifuge-simulated commercial spaceflight in a subject with hemophilia A. Aerosp Med Hum Perform. 2023; 94(6):470-474.

αKlotho decreases after reduced weight-bearing from both spaceflight and hindlimb unloading.

Alpha(α)Klotho, a soluble transmembrane protein, facilitates calcium-phosphorus homeostasis through feedback between bone and kidney and is a potential systemic biomarker for bone-kidney health during spaceflight. We determined if: (1) plasma αKlotho was reduced after both spaceflight aboard the ISS and hindlimb unloading (HU); and (2) deficiency could be reversed with exercise. Both spaceflight and HU lowered circulating plasma αKlotho: plasma αKlotho recovered with exercise after HU.

Albumin, oral contraceptives, and venous thromboembolism risk in astronauts.

A venous thromboembolism (VTE) event occurred in a female astronaut during long-duration spaceflight. Multiple factors may have contributed to this risk, including the use of combined (progestin + estrogen) oral contraceptives (cOC). Biochemistry data from 65 astronauts were evaluated for associations with cOC use and with sex. The female astronauts who used cOCs had lower concentrations of serum albumin and higher concentrations of transferrin, a protein involved in the clotting cascade, than the male astronauts and the female astronauts who were not taking cOCs (P < 0.001). The women who used cOCs had higher serum concentrations of the acute phase reactant ceruloplasmin and cortisol during flight (P < 0.001) than the men and the women who were not taking cOCs; they also had higher calculated whole blood viscosity than women not taking cOCs (P < 0.001). Lower circulating concentrations of albumin, higher concentrations of transferrin, and elevated markers of inflammation all could contribute to an increased risk of VTE during spaceflight. These changes, in association with a higher blood viscosity, can directly affect endothelial glycocalyx integrity and hypercoagulability status, both of which contribute to VTE risk in terrestrial populations.NEW & NOTEWORTHY We report here evidence of an association between oral contraceptive use and serum albumin, among other factors, which potentially increase the risk of venous thromboembolism in astronauts. These findings highlight potential risks to astronaut health while providing potential alternative countermeasures for decreasing VTE risk during spaceflight. These findings also highlight an underrecognized potential mechanism for hypoalbuminemia to increase VTE risk in terrestrial populations.

Everything you wanted to know about space radiation but were afraid to ask.

The space radiation environment is a complex combination of fast-moving ions derived from all atomic species found in the periodic table. The energy spectrum of each ion species varies widely but is prominently in the range of 400-600 MeV/n. The large dynamic range in ion energy is difficult to simulate in ground-based radiobiology experiments. Most ground-based irradiations with mono-energetic beams of a single one ion species are delivered at comparatively high dose rates. In some cases, sequences of such beams are delivered with various ion species and energies to crudely approximate the complex space radiation environment. This approximation may cause profound experimental bias in processes such as biologic repair of radiation damage, which are known to have strong temporal dependencies. It is possible that this experimental bias leads to an over-prediction of risks of radiation effects that have not been observed in the astronaut cohort. None of the primary health risks presumably attributed to space radiation exposure, such as radiation carcinogenesis, cardiovascular disease, cognitive deficits, etc., have been observed in astronaut or cosmonaut crews. This fundamentally and profoundly limits our understanding of the effects of GCR on humans and limits the development of effective radiation countermeasures.

Real-Time Culture-Independent Microbial Profiling Onboard the International Space Station Using Nanopore Sequencing.

For the past two decades, microbial monitoring of the International Space Station (ISS) has relied on culture-dependent methods that require return to Earth for analysis. This has a number of limitations, with the most significant being bias towards the detection of culturable organisms and the inherent delay between sample collection and ground-based analysis. In recent years, portable and easy-to-use molecular-based tools, such as Oxford Nanopore Technologies' MinION™ sequencer and miniPCR bio's miniPCR™ thermal cycler, have been validated onboard the ISS. Here, we report on the development, validation, and implementation of a swab-to-sequencer method that provides a culture-independent solution to real-time microbial profiling onboard the ISS. Method development focused on analysis of swabs collected in a low-biomass environment with limited facility resources and stringent controls on allowed processes and reagents. ISS-optimized procedures included enzymatic DNA extraction from a swab tip, bead-based purifications, altered buffers, and the use of miniPCR and the MinION. Validation was conducted through extensive ground-based assessments comparing current standard culture-dependent and newly developed culture-independent methods. Similar microbial distributions were observed between the two methods; however, as expected, the culture-independent data revealed microbial profiles with greater diversity. Protocol optimization and verification was established during NASA Extreme Environment Mission Operations (NEEMO) analog missions 21 and 22, respectively. Unique microbial profiles obtained from analog testing validated the swab-to-sequencer method in an extreme environment. Finally, four independent swab-to-sequencer experiments were conducted onboard the ISS by two crewmembers. Microorganisms identified from ISS swabs were consistent with historical culture-based data, and primarily consisted of commonly observed human-associated microbes. This simplified method has been streamlined for high ease-of-use for a non-trained crew to complete in an extreme environment, thereby enabling environmental and human health diagnostics in real-time as future missions take us beyond low-Earth orbit.

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.

Limitations in predicting the space radiation health risk for exploration astronauts.

Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight.

Medical Implications of Space Radiation Exposure Due to Low-Altitude Polar Orbits.

INTRODUCTION: Space radiation research has progressed rapidly in recent years, but there remain large uncertainties in predicting and extrapolating biological responses to humans. Exposure to cosmic radiation and solar particle events (SPEs) may pose a critical health risk to future spaceflight crews and can have a serious impact on all biomedical aspects of space exploration. The relatively minimal shielding of the cancelled 1960s Manned Orbiting Laboratory (MOL) program's space vehicle and the high inclination polar orbits would have left the crew susceptible to high exposures of cosmic radiation and high dose-rate SPEs that are mostly unpredictable in frequency and intensity. METHODS: In this study, we have modeled the nominal and off-nominal radiation environment that a MOL-like spacecraft vehicle would be exposed to during a 30-d mission using high performance, multicore computers. RESULTS: Projected doses from a historically large SPE (e.g., the August 1972 solar event) have been analyzed in the context of the MOL orbit profile, providing an opportunity to study its impact to crew health and subsequent contingencies. DISCUSSION: It is reasonable to presume that future commercial, government, and military spaceflight missions in low-Earth orbit (LEO) will have vehicles with similar shielding and orbital profiles. Studying the impact of cosmic radiation to the mission's operational integrity and the health of MOL crewmembers provides an excellent surrogate and case-study for future commercial and military spaceflight missions.Chancellor JC, Auñon-Chancellor SM, Charles J. Medical implications of space radiation exposure due to low-altitude polar orbits. Aerosp Med Hum Perform. 2018; 89(1):3-8.