Modeling sex-dependent cardiovascular responses to lower body negative pressure

Bergauer, Andrej (author), Urevc, Janez (author), Halilovič, Miroslav (author), Batzel, Jerry J. (author), Pivec, Vid (author), Goswami, Nandu (author)

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.

• Language: English
• Keywords: cardiovascular system, hemodynamics, computational modeling, baroregulation, sex differences, lower body negative pressure
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FS - Faculty of Mechanical Engineering
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. H240-H259
• Numbering: Vol. 331, iss. 1
• PID: 20.500.12556/RUL-184107
• UDC: 612.1:519.6
• ISSN on article: 0363-6135
• DOI: 10.1152/ajpheart.00258.2026
• COBISS.SI-ID: 280868611
• Publication date in RUL: 29.06.2026

Record is a part of a journal

• Title: American journal of physiology : heart and circulatory physiology
• Shortened title: Am J Physiol Heart Circ Physiol
• Publisher: American Physiological Society.
• ISSN: 0363-6135
• COBISS.SI-ID: 24932096

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: srčno žilni sistem, hemodinamika, matematično modeliranje, baroregulacija, razlika med spoloma, negativni tlak

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: European Space Agency
• Project number: 4000137614/22/NL/SC
• Name: Prediction model of countermeasures efficiency on cardiovascular system and fluid shifting in simulated microgravity conditions