Dose-dependent effects of graded altered gravity during hypovolaemia on central haemodynamics and cardiovascular...

The cardiovascular system is strongly influenced by gravitational loading and blood volume status. Quantifying central haemodynamic and autonomic reflex responses to fluid redistribution is important in altered-gravity conditions, with relevance to spaceflight and clinical medicine. However, the continuous physiological response to graded gravitational loading under hypovolaemia has not been characterized. Here, we used graded tilt to derive continuous dose-response relationships to altered gravity during acute hypovolaemia. Sixteen healthy adults (8 males, 25 ± 2 years; 8 females, 23 ± 1 years) completed a graded tilt protocol from 45° head-down to 45° head-up in 15° increments, before and after oral furosemide administration (40 mg). Steady-state haemodynamics and heart-rate variability (HRV) were assessed at seated and supine baselines and at each tilt angle. Hypovolaemia (15.3 ± 0.2% reduction in plasma volume) increased heart rate and total peripheral resistance, while stroke volume and cardiac output decreased, with no significant change in arterial pressure. HRV decreased in the time domain and shifted towards sympathetic predominance in the frequency domain. Continuous dose-response curves were generated by projecting the gravitational vector along the cranio-caudal axis across tilt, enabling inclusion of Moon (∼0.17G at 9° head-up) and Mars (∼0.38G, at 22° head-up) equivalent gravity levels within the model. These findings provide an integrative continuous cardiovascular dose-response framework for altered gravity under hypovolaemia. This framework may help guide development of countermeasures across specific gravitational loads and inform conditions in which orthostatic stress and impaired volume regulation coexist.