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Abstract INTRODUCTION: 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.

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.

Background: Intermittent artificial gravity (AG) training over days and weeks has been shown to improve the human orthostatic tolerance limit (OTL) and improve cardiovascular regulation in response to orthostatic stress. Effects of a single AG exposure are currently unknown., Methods: We tested cardiovascular responses to orthostatic stress in 16 hypovolemic subjects (9 men and 7 women), once following a single, short (∼90 min) bout of AG and once following a similar period of head-down bed rest (HDBR). Hypovolemia was produced by intravenous furosemide infusion (20 mg) and orthostatic stress was produced by combined 70° head-up tilt (HUT) and progressively increasing lower body negative pressure until symptoms of presyncope developed. To assess reflex-induced changes in cardiovascular regulation, heart rate and blood pressure variability were analyzed by spectral analysis and baroreflex activity was evaluated by transfer function analysis., Results: Compared to HDBR, a short AG exposure increased men's low frequency (0.04-0.15 Hz) power of systolic blood pressure (SBPLF), but did not change women's SBPLF responses to orthostatic stress. In response to 70° HUT, compared to supine, low frequency phase delay (PhaseLF) between systolic blood pressure and RR intervals increased by ∼20% following HDBR, but did not change following AG, reflecting improved baroreflex activity at a milder level of orthostatic stress after AG., Conclusions: These results indicate that a short bout of AG increased both sympathetic and baroreflex responsiveness to orthostatic stress in hypovolemia-induced, cardiovascular-deconditioned men and women, which may contribute to the AG-induced improvement of OTL shown in our previous reports.Zhang Q, Evans JM, Stenger MB, Moore FB, Knapp CF. Autonomic cardiovascular responses to orthostatic stress after a short artificial gravity exposure. Aerosp Med Hum Perform. 2017; 88(9):827-833.

Introduction: Cardiovascular deconditioning apparently progresses with flight duration, resulting in a greater incidence of orthostatic intolerance following long-duration missions. Therefore, we anticipated that the proportion of astronauts who could not complete an orthostatic tilt test (OTT) would be higher on landing day and the number of days to recover greater after International Space Station (ISS) than after Space Shuttle missions., Methods: There were 20 ISS and 65 Shuttle astronauts who participated in 10-min 80° head-up tilt tests 10 d before launch, on landing day (R+0), and 3 d after landing (R+3). Fisher's Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the OTT. Cox regression was used to identify cardiovascular parameters associated with OTT completion and mixed model analysis was used to compare the change and recovery rates between groups., Results: The proportion of astronauts who completed the OTT on R+0 (2 of 6) was less in ISS than in Shuttle astronauts (52 of 65). On R+3, 13 of 15 and 19 of 19 of the ISS and Shuttle astronauts, respectively, completed the OTT. An index comprised of stroke volume and diastolic blood pressure provided a good prediction of OTT completion and was altered by spaceflight similarly for both astronaut groups, but recovery was slower in ISS than in Shuttle astronauts., Conclusions: The proportion of ISS astronauts who could not complete the OTT on R+0 was greater and the recovery rate slower after ISS compared to Shuttle missions. Thus, mission planners and crew surgeons should anticipate the need to tailor scheduled activities and level of medical support to accommodate protracted recovery after long-duration microgravity exposures.