INTRODUCTION: Microgravity exposure alters the hydrostatic pressure gradient in the body, inducing a headward fluid shift. This affects cardiovascular autonomic function, leading to an increased risk of orthostatic intolerance [1][2]. Short-term exposures to weightlessness are becoming more prevalent with the growth of commercial spaceflight. Therefore, this study aims to investigate the initial autonomic response during the first 60 minutes of exposure to a simulated microgravity environment using 6º head-down tilt (HDT).

METHOD: Eleven subjects (6F/5M, mean age ± standard deviation: 25.4 ± 3.9 years old) were exposed to 60 minutes of 6º HDT. Several autonomic and hemodynamic indices were collected every 10 minutes during the 60-minute 6º HDT exposure. Data collected include standard deviation of all NN intervals (SDNN), root mean square of adjacent NN interval differences (RMSDD), heart rate variability triangular index (HRVTi), low frequency power (LF), high frequency power (HF), normalized low frequency power (LFn), normalized high frequency power (HFn), normalized low frequency-high frequency ratio (LF-HFn), baroreceptor sensitivity (BRS), mean arterial pressure (MAP) and heart rate (HR), all of which were collected with a Finapres NOVA. In addition, cardiac output (CO) and stroke volume (SV) were collected using an Innocor device. Measurements at the beginning and end of exposure were analyzed using paired t-tests or the Wilcoxon Signed Rank test when parametric assumptions were not met. Results are presented as mean ± standard error.

RESULTS: Preliminary results suggest that there were no significant changes in autonomic variables during 60 minutes of 6º HDT (SDNN = 66.8±6.3 to 63.7±4.8 (p=0.437), RMSDD = 42.1±7.2 to 41.5±6.3 (p=0.783), HRVTi = 14.7±1.5 to 15.0±0.7 (p=0.798), LFn = 64.8±4.7 to 70.5±3.5 Hz (p=0.081), HFn = 35.2±4.7 to 29.5±3.5 Hz (p=0.081), LF-HFn = 2.5±0.5 to 3.0±0.6 (p=0.054), and BRS = 13.7±3.5 to 15.3±1.9 (p=0.413)). MAP significantly increased from 71.9±2.8 to 79.3±2.2 mmHg (p=0.002) and SV significantly increased from 64.7±5.8 to 71.7±4.8 mL (p=0.018). No significant changes were observed in HR (73.4±4.2 to 72.5±3.1 BPM, p=0.669).

DISCUSSION: The autonomic response does not seem to evolve during the first 60 minutes of headward fluid shift exposure. However, significant increases were observed in the associated hemodynamic responses (i.e., MAP and SV). These results contribute to the understanding of the physiological responses elicited by short microgravity exposures and inform the development of human countermeasures for future human spaceflight missions.

Introduction
Potential consequences of prolonged microgravity exposure to lower limb perfusion, may present in the same way as ischaemic disease¹. Complications of ischaemia in the lower limb are known to include pain – effecting mobility and quality of life, and tissue death – presenting as ulceration and gangrene. Healing of traumatic wound injuries is also likely to be impaired until reperfusion takes place. When wound healing is delayed, risk of further complications such as infection and limb amputation increases². With an anticipated increase in human involvement in future space projects and the potential for future space tourism, the development of rapid assessment and risk modification strategies are essential³.

Methods
This observational study simultaneously measured key factors used to determine lower limb perfusion: peripheral arterial oxygen saturation (Sp02%), capillary bed oxygen saturation (S02%), toe systolic blood pressure (mm/hg) and peripheral skin temperature(°C). The experiment was conducted onboard a parabolic flight and lower limb perfusion values were compared from periods of steady flight (1G) hypergravity (1.75G+) and microgravity (<0.05G). Four pieces of frequently used clinical equipment were secured to each participants’ foot and perfusion continuously monitored for five parabolas. A Friedmans test of variance was used to explore the impact different gravitational conditions had on the lower limb perfusion values obtained.

Results
18 healthy participants (10 male, 8 female) took part in the experiment. When comparing lower limb perfusion values to 1G (control) the study found: 1) no significant difference between Sp02 values in hyper or microgravity was detected when using a pulse oximeter; 2) a significant difference in S02 in microgravity was detected by white light spectroscopy; 3) a significant difference in skin temperature of the foot was detected by thermography in both hyper and microgravity with the lowest mean temperatures recorded in microgravity (19.6⁰C).

Conclusion
This study found evidence that S02 and peripheral skin temperature decreases in microgravity compared to 1G, suggesting a reduction in blood flow. White light spectroscopy and thermography devices demonstrated they functioned the same in altered gravity conditions offering a quick, reliable method of assessing the acute effects of hyper and microgravity on lower limb perfusion. These methods may be useful to predict healing potential when injuries occur and highlight early warning signs of tissue damage due to poor perfusion. However, additional work to further establish the impact on lower limb micro circulation in sustained microgravity and whether vascular adaptation occurs, would be beneficial.

For the first time in more than 60 years of human spaceflight, a deep venous thrombus (DVT) was identified in an astronaut during an International Space Station mission. The incidental finding occurred during remotely-guided ultrasound imaging of the left internal jugular vein (IJV) by a research team studying hemodynamics in weightlessness and was confirmed by a second, medically-directed ultrasound examination with compression. The astronaut was successfully managed on-orbit using anti-coagulation and was safely returned to Earth without further complications. Although a postflight inherited thrombophilia evaluation was negative, a potential risk factor for the DVT that was identified was the use of estrogen-containing contraception. However, use of oral contraceptives to suppress menses is not a new practice in spaceflight and may not be the causative factor for this issue. Indeed, a suspected partially-occlusive DVT was identified in the left IJV of another astronaut who was not taking oral contraceptives, though diagnosis of DVT in this second individual was not confirmed with standard diagnostic practices because the identification was made during a retrospective review of research imaging. Several peer-reviewed publications have described factors that might contribute to venous thrombosis during spaceflight, but data from original research and medical surveillance are limited. Hypotheses regarding the mechanisms of venous thrombosis during spaceflight have included a strong emphasis on those factors described by Virchow’s Triad: flow stasis, hypercoagulability, and endothelial dysfunction and/or vessel wall damage. Recent observations of left IJV flow stasis in brief periods of weightlessness during parabolic flight suggest that conditions that could contribute to thrombus development may occur early in spaceflight and may be directly related to headward fluid shift and movement of organs and vessels in the thoracic cavity and neck. To date, biomarkers of hemostasis have not clearly differentiated the definitive and potential IJV thrombus cases from 12 other astronauts in the same study, and stasis was observed >30% of all participants. Subsequently, a venous surveillance protocol was initiated by NASA Space Medicine, and no additional thrombus cases in NASA crewmembers have been observed to date. Given that the confirmed and suspected cases of IJV thrombus in 2 astronauts during spaceflight were asymptomatic, the actual incidence of DVT remains unknown in the 88 NASA astronauts who have flown on ISS for >30 days, and the etiology requires further investigation.

Ultrasound (US) as an imaging modality has expanded rapidly in recent decades finding itself in the hands clinicians for point-of-care ultrasound (POCUS). Proven beneficial in isolated and austere environments including micogravity since 1982. Onboard the International space station (ISS), US has solidified its place as the imaging modality of choice being versatile, small volume and low power, as well as non-invasive with non-ionising radiation.

As we look to travel beyond lower earth orbit (LEO) to the Moon and Mars we need to change the paradigm of how we practice medicine, including the use of newer technologies and the training of crew members.

US has been used in space for several decades now, albeit exclusively in LEO and likely will be the diagnostic tool of choice for exploration missions. Currently, POCUS training in microgravity is based on a ‘just-in-time’ training model with real time remote guidance from experts, with some basic training for crew medical officers. Additional challenges include delayed communication, limited resources and no immediate evacuation for definitive care. This will force crews to be more autonomous during medical emergencies.

POCUS has good diagnostic accuracy for a range of pathologies in different organ systems, including cardiac, pulmonary, vascular, and intra-abdominal. US has been shown to be superior to X-ray in detection of life-threatening pathologies, such as pneumothorax, pulmonary oedema, tamponade and pleural effusions, and comparable to computed tomography.

Integrating artificial intelligence (AI) systems to support image capture and interpretation can help bridge gaps in training. AI shows promise in healthcare, but US is highly operator dependent with image variability, both in +1Gz and then there is the complexity of body fluid distribution in microgravity.

Our review continues the discussion into research for enhanced medical training in POCUS. Research is needed to determine optimal training duration with POCUS to be automonous, also how to maintain skill retention. This can be done using ground-based analogues and ISS. Can also learn from terrestrial accreditation pathways for POCUS. We need research to assess the practicality and usefulness of AI in aiding image acquisition and diagnostic interpretation, potentially needing large microgravity data sets.

As the space sector grows, integrating POCUS technology and medical training will be essential. There will be debate amongst space experts on the optimal training. But a combination of increased hours of medical and POCUS training combined with enhanced hardware and AI will equip crews for autonomous medical capabilities for exploration missions.

INTRODUCTION
Pathology-induced left ventricular shape alterations, with increased left ventricular sphericity index, are determinants of mitral valve dysfunction [1, 2]. Long-term exposure to microgravity can lead to cardiac muscle atrophy and alter cardiac function [3, 4]. Furthermore, long-term exposure to microgravity has been shown to increase the left ventricular sphericity index [5, 6]. This research project investigates the impact of long-term spaceflight on mitral valve-related parameters.

METHOD
We conducted a before-after study on nine male cosmonauts, aged 44 ± 6 years, with a BMI of 26.28 ± 1.83 kg/m², spending an average of 247 days on the International Space Station (ISS) between 2020 and 2023. A cardiac MRI, without contrast agents, was performed at the Medical Educational and Scientific Center University Hospital in Moscow. Cosmonauts were scanned in the supine position using retrospective electrocardiography-gated multi-breath-hold balanced steady-state free precession cine sequences, including two-chamber (2CV) and four-chamber (4CV) views. Each slice comprised 25 cardiac phases. The procedure was repeated before (60 ± 30 days prior to launch) and after (6 ± 2 days after landing) ISS missions. CAAS MR Solutions 5.1.2. software was used for MRI data analysis. Mitral leaflet billowing (> 2 mm systolic protrusion [7]) was assessed in the 2CV view, and a quantification was done if the billowing was present. Mitral annulus diameter was assessed in end-systole and end-diastole in the two cine views. Statistical analysis employed paired t-tests (p < 0.05). Compliance with test conditions was ensured before analysis.

RESULT
Post-flight, billowing was present for five cosmonauts (see Table 1), without prolapse and without thickening of the leaflet. The mitral annulus diameter was larger post-flight than pre-flight. This dilation was observed in end-systole and end-diastole, both in 2CV and 4CV (see Table 1 and Figure 1).

CONCLUSION
This study shows alterations of the mitral valve after long-term exposure to microgravity. Moreover, billowing was present on five out of nine cosmonauts. This highlights additional alteration of the valve, however not systematically present on this cohort of cosmonauts. Subsequent investigations need to assess if those mitral modifications could lead to mitral valve regurgitation and if an even prolonged exposure to microgravity could worsen those alterations.

Artemis astronauts returning to the Moon will experience head-to-foot (+Gz) accelerations during the descent to and ascent from the lunar surface. Weightlessness induced cardiovascular deconditioning increases the risk of orthostatic intolerance (OI) during +Gz exposures. Given that females are more susceptible to OI when re-exposed to 1-G, the effect of sex on OI and OI countermeasures (CM) must be considered for these missions. Compression garments are used as an OI CM after spaceflight, but data are limited in females. The goals of this study are to to assess the effect of sex on 1) OI and 2) the efficacy of the Orion orthostatic intolerance garment (OIG), over a range of hydrostatic pressure challenges simulating the range of +Gz anticipated during Artemis missions. Thirty-eight (19 females) healthy participants will be recruited to participate. First, baseline OI will be assessed using a 20-minute 80° head-up tilt (HUT) test. Second, we will induce hypovolemia (20mg furosemide) and participants will complete three HUT tests (20-min or until presyncope) simulating 0.50-, 0.75- and 1.00-Gz, (randomized order). Finally, participants will complete the same protocol, while wearing a custom-built OIG. Plasma volume, tilt tolerance time, blood pressure, heart rate and stroke volume will be measured. To date, ten participants (36.8±8.8 years, 178.0±12.4 cm, 75.5±12.2 kg) have completed this study. Two males and four females became presyncopal during the baseline 80° HUT. Infusion of furosemide reduced plasma volume by 11.7 ± 2.0 and 13.0 ± 0.8 % in males and females, respectively. While hypovolemic without the OIG, four males and two females became presyncopal at 80° HUT, and three males and two females became presyncopal at 50° HUT. One male became presyncopal at 30° HUT. Females became presyncopal earlier than males during 0.5, 0.75 and 1-Gz tilts. While hypovolemic with the OIG all, participants tested to date completed the HUT at each angle. Based on the preliminary data, OI occurs in males and females simulated 0.50-, 0.75- and 1.00-Gz without the OIG and females appear to be more susceptible to OI. Further, the OIG appears effective in mitigating OI across the range of G-levels expected during descent to and ascent from the lunar surface.