Integrative cardiovascular dose-response to graded lower body negative pressure
BackgroundLower body negative pressure (LBNP) has been posited as a potential spaceflight countermeasure to counteract the physiological deconditioning related to fluid shifts in micro-gravity. However, open questions remain as to 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. MethodsTwenty-four subjects (12M, 12F) were exposed to graded LBNP from 0 mmHg to -50 mmHg in 10 mmHg increments, both in supine (0{degrees}) and 15{degrees} head-down tilt postures. We measured the steady-state response in a large range of variables, including those related to the systemic circulation, cardiovascular control, and hemodynamics of the eyes and neck. ResultsBuilding on the experimental data, dose-response curves were constructed using a Bayesian multivariate hierarchical modeling 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. Further, we demonstrated the potential for LBNP to reduce jugular venous flow stagnation, which is considered one of the major health risks during human spaceflight. ConclusionsThe 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. Key Points SummaryO_LILower body negative pressure (LBNP) has been posited as a potential countermeasure for multiple risks associated with spaceflight, including cardiovascular deconditioning, spaceflight-associated neuro-ocular syndrome, and venous thromboembolism events. However, the specific LBNP dose needed to mitigate these risks is still unknown. C_LIO_LIWe constructed the LBNP dose-response curves in supine and 15{degrees} head-down-tilt positions to quantify the acute response of a large variety of hemodynamics, autonomic, ocular, and neck variables across a range of LBNP levels. C_LIO_LIWe also used a Bayesian multivariate modeling framework to identify significant relationships between variables and to compare their effect sizes under different levels of LBNP. C_LIO_LIIn addition, results indicate that LBNP is a promising countermeasure to reduce jugular venous flow stagnation occurring during microgravity exposure. C_LIO_LIThis study constitutes the most comprehensive analysis of cardiovascular hemodynamics, autonomic, and cephalad response to LBNP to date. This framework informs the development of countermeasures to mitigate the detrimental effects of spaceflight. C_LI