Ocular And Jugular Gravitational Dose-Response Curves During Hypovolemia: Preliminary Results

Introduction: During spaceflight, astronauts are exposed to several risks and concerns associated with microgravity exposure, including spaceflight associated neuro-ocular syndrome, stagnant or retrograde blood flow in the internal jugular vein (IJV), and an increased risk of venous thrombosis. The chronic redistribution of fluid experienced in microgravity and subsequent relative hypovolemia are hypothesized to contribute to these deleterious effects. The present study aims to characterize: (1) the ocular and jugular vein responses of subjects exposed to a range of fluid shifts (using a tilt paradigm) (2) the effect of induced hypovolemia, and (3) the differences in response between women and men. Methods: This protocol propose to construct dose-response curves in deconditioned participants, either by drug-induced acute hypovolemia or by 48h 6° head-down bed rest, as a model of microgravity. In the present work, we discuss preliminary results (n=6; 5M/1F) from the drug-induced hypovolemia campaign (40mg oral furosemide diuretic). Before and 3 hours after ingestion of furosemide, participants are tilted in 15° increments from 45° head-down tilt (HDT) to 45° head-up tilt (HUT) to construct gravitational dose-response curves. Measurements at each tilt angle include IJV cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Results: The diuretic protocol led to a significant hypovolemia after 3h (–16±3% in plasma volume, paired t-test p=0.001). We observed a general decrease in stroke volume and cardiac output (ANOVA drug effect p<0.001) and an increase in heart rate (p<0.001) compared to control tilt. We also observed a non-linear gravitational dependence of the IOP, and IJV CSA and a linear dependence of the IJV pressure. IOP globally decreased during hypovolemia (Control: from 33.6±1.1 at 45°HDT to 12.2±1.0 mmHg at 45°HUT, Hypovolemia: from 27.1±1.9 at 45°HDT to 11.2±1.6 mmHg at 45°HUT, angle effect p<0.001 and drug effect p=0.003). The IJV pressure had a global tendency to decrease during hypovolemia (Control: from 57.0±2.6 at 45°HDT to 7.3±3.4 mmHg at 45°HUT, Hypovolemia: from 49.9±5.1 at 45°HDT to 9.5±3.0 mmHg at 45°HUT, angle effect p<0.001 and drug effect p=0.06). Finally, the IJV CSA did not decrease significantly with hypovolemia (Control: from 134±7 at 45°HDT to 14±5 mm 2 at 45°HUT, Hypovolemia: from 126±20 at 45°HDT to 12±3 mm 2 at 45°HUT, angle effect p<0.001 and drug effect p=0.117) Discussion: In the present study, the observed hypovolemia closely mimics a microgravity exposure. During spaceflight, decrease in plasma volume and fluid redistributions are part of the main factors contributing to the cardiovascular deconditioning and ocular alterations in astronauts. At the end of the study, a comprehensive framework will be proposed for cephalic cardiovascular and ocular responses to gravitational vector changes before and after hypovolemia. This ground model will contribute to assess spaceflight induced changes in men and women. This work is supported by the Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.