dc.description.abstract | The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. For future long-duration spaceflight, these gravitational effects could be related to decreased cardiovascular performance, the pathoetiology of spaceflight associated neuro-ocular syndrome (SANS), and increased venous thromboembolism (VTE) risk. The development of novel countermeasure protocols using, for example, lower body negative pressure (LBNP) or short-radius centrifugation (SRC) requires a full understanding of the detailed cardiovascular response to gravity and to different levels of countermeasure intervention.
In this research effort, we use a complementary experimental and modeling approach to generate acute dose-response curves for systemic, autonomic, and cephalad parameters of the cardiovascular system in graded tilt (as an analog for altered-gravity), graded LBNP, and graded SRC. In the experimental approach, 24 subjects (12 male and 12 female) experienced 1) a graded tilt profile in the range of 45° head-up tilt to 45° head-down tilt in 15° increments; and 2) a graded LBNP profile from 0 mmHg to –50 mmHg in 10 mmHg increments. Using two different statistical techniques (mixed-effects modeling and Bayesian hierarchical multivariate modeling) we generate dose-response curves for the cardiovascular and ocular response. In the computational approach, we further develop an existing lumped-parameter model of the cardiovascular system to incorporate cephalad hemodynamics and the effects of body tissue weight. In addition, we also further develop a complementary lumped-parameter model of the eye. We simulate the same tilt and LBNP profiles, along with a graded SRC profile and a gravitational field change using simulated 50th percentile male and female subjects.
The quantification of cardiovascular hemodynamics as a function of changes in the gravitational vector or the presence of countermeasure interventions presented here provides a terrestrial model to reference spaceflight-induced changes, contributes to the assessment of the pathogenesis of SANS and spaceflight VTE events, and informs the development of countermeasures. | |