Modeling sex-dependent cardiovascular responses to lower body negative pressure.

Lower body negative pressure (LBNP) induces controlled central hypovolemia, yet the regional mechanisms of cardiovascular compensation remain difficult to resolve experimentally. This study presents a computational framework for estimating regional parameter changes consistent with observed hemodynamic responses to progressive LBNP using a refined lumped-parameter model calibrated to experimental data. Hemodynamic responses to graded LBNP (0 to -40 mmHg) and recovery were obtained from a previously published experimental study in 35 healthy adults (17 females, 18 males), including heart rate, cardiac output, arterial pressure, total peripheral resistance, and ultrasound-derived internal jugular and portal venous flow. The model was structurally refined by separating head and arm circulations, enabling explicit modeling of cerebral venous outflow and jugular vein dynamics, and calibrated using a sensitivity- and correlation-guided identification strategy. Baseline calibration revealed distinct vascular architectures, with males exhibiting higher arterial compliance and dominant lower-body resistance, and females showing greater splanchnic and renal tone. During progressive LBNP, the identified splanchnic resistance increased monotonically in both sexes, whereas lower-body resistance rose markedly in males but remained near baseline in females, indicating sex-dependent compensation strategies. The calibrated model quantifies regional vascular resistance changes and venous blood volume redistribution during hypovolemia, providing a model-based interpretation of possible regulatory mechanisms into sex-specific cardiovascular regulation that cannot be directly measured in vivo.NEW & NOTEWORTHY We present the first lumped-parameter cardiovascular model calibrated to sex-specific hemodynamic responses during graded lower body negative pressure, integrating internal jugular and portal venous flow as calibration targets. Baseline identification reveals coherent structural sex differences: females exhibit higher splanchnic and renal vascular resistance, and males exhibit higher lower-limb resistance and arterial compliance. Across all LBNP levels, splanchnic vasoconstriction emerges as the dominant compensatory pathway in both sexes, whereas lower-limb resistance diverges markedly between sexes.