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However, open questions remain regarding the magnitude of LBNP that should be applied. We systematically characterized the cardiovascular effects of LBNP and quantified the effect size of varied LBNP doses across different parts of the cardiovascular system. Twenty\u2010four subjects (12\u00a0male and 12 female) were exposed to graded LBNP, increasing from 0 to \u221250\u00a0mmHg in 10\u00a0mmHg increments, in both supine (0\u00b0) and 15\u00b0 head\u2010down tilt postures. At each pressure level, subjects first underwent a 6\u00a0min stabilization period to reach a steady\u2010state cardiovascular response. We then assessed a wide range of variables, including those related to the systemic circulation, cardiovascular control, and haemodynamics of the eyes and neck. Building on the experimental data, dose\u2013response curves were constructed using a Bayesian multivariate hierarchical modelling framework to quantify the effect size of every variable considered when subjected to LBNP. The methodology allows direct comparison of the variables and the underlying structural relationships between them. Furthermore, we demonstrated the potential for LBNP to reduce jugular venous flow stagnation, which is considered one of the major health risks during human spaceflight. The dose\u2013response curves and effect sizes generated from this research effort establish the most comprehensive framework available to date that characterizes physiological responses to LBNP. These results directly inform the development of countermeasures to mitigate the negative effects of spaceflight, including cardiovascular deconditioning, spaceflight\u2010associated neuro\u2010ocular syndrome and venous thromboembolism events.<\/jats:p>","DOI":"10.1113\/ep092483","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T01:40:58Z","timestamp":1747273258000},"page":"1852-1879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrative cardiovascular dose\u2013response to graded lower\u2010body negative pressure"],"prefix":"10.1113","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7437-5433","authenticated-orcid":false,"given":"Richard S.","family":"Whittle","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering University of California  Davis California USA"},{"name":"Department of Aerospace Engineering Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-5010","authenticated-orcid":false,"given":"Nathan","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Sport Management Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-6964","authenticated-orcid":false,"given":"Eric A.","family":"Hall","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine (EnMed) Texas A&amp;M University  College Station Texas USA"},{"name":"Department of Biomedical Engineering Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiyya","family":"Patanam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie J.","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Department of Aerospace Engineering Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-9327","authenticated-orcid":false,"given":"Ana","family":"Diaz\u2010Artiles","sequence":"additional","affiliation":[{"name":"Department of Aerospace Engineering Texas A&amp;M University  College Station Texas USA"},{"name":"Department of Kinesiology and Sport Management Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0000000000001095"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0267659112436631"},{"key":"e_1_2_10_4_1","volume-title":"Directed acyclic graphs: A tool for understanding the NASA human spaceflight system risks","author":"Antonsen E. 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