Integrative cardiovascular dose-response to graded lower-body negative pressure

Lower-body negative pressure (LBNP) has been posited as a potential spaceflight countermeasure to counteract the physiological deconditioning related to fluid shifts in microgravity. 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-four subjects (12 male and 12 female) were exposed to graded LBNP, increasing from 0 to -50 mmHg in 10 mmHg increments, in both supine (0 degrees) and 15 degrees head-down tilt postures. At each pressure level, subjects first underwent a 6 min stabilization period to reach a steady-state 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-response 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-response 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-associated neuro-ocular syndrome and venous thromboembolism events.