Modeling individual differences in cardiovascular response to gravitational stress using a sensitivity analysis

Abstract

The human cardiovascular (CV) system elicits a physiological response to gravitational environments, with significant variation between different individuals. Computational modeling can predict CV response, however model complexity and variation of physiological parameters in a normal population makes it challenging to capture individual responses. We conducted a sensitivity analysis on an existing 21-compartment lumped-parameter hemodynamic model in a range of gravitational conditions to 1) investigate the influence of model parameters on a tilt test CV response and 2) to determine the subset of those parameters with the most influence on systemic physiological outcomes. A supine virtual subject was tilted to upright under the influence of a constant gravitational field ranging from 0g to 1g. The sensitivity analysis was conducted using a Latin Hypercube Sampling/Partial Rank Correlation Coefficient methodology with subsets of model parameters varied across a normal physiological range. Sensitivity was determined by variation in outcome measures including heart rate, stroke volume, central venous pressure, systemic blood pressures, and cardiac output. Results showed that model parameters related to the length, resistance, and compliance of the large veins and parameters related to right ventricular function have the most influence on model outcomes. For most outcome measures considered, parameters related to the heart are dominant. Results highlight which model parameters to accurately value in simulations of individual subjects' CV response to gravitational stress, improving the accuracy of predictions. Influential parameters remain largely similar across gravity levels, highlighting that accurate model fitting in 1g can increase the accuracy of predictive responses in reduced gravity.