Unraveling autonomic cardiovascular control complexity during orthostatic stress: Insights from a mathematical model

Understanding cardiovascular control mediated by the autonomic system remains challenging due to its inherent complexity. Consequently, syndromes such as orthostatic intolerance continue to evoke debates regarding the underlying pathophysiological mechanisms. This study develops a comprehensive mathematical model simulating the control of the sympathetic branch of the cardiovascular system in individuals with normal and abnormal responses to the head-up-tilt test. We recruited four young women: one control, one with vasovagal syncope, one with orthostatic hypertension, and one with orthostatic hypotension, exposing them to an orthostatic head-up tilt test (HUTT) employing non-invasive methods to measure electrocardiography and continuous blood pressure. Our work encompasses a compartmental model formulated using a system of ordinary differential equations. Using heart rate as input, we predict blood pressure, flow, and volume in compartments representing the veins, arteries, heart, and the sympathetic branch of the baroreflex control system. The latter is modulated by high- and low-pressure baroreceptor afferents activated by changes in blood pressure induced by the HUTT. Sensitivity analysis, parameter subset selection, and optimization are employed to estimate patient-specific parameters associated with autonomic performance. The model has seven sensitive and identifiable parameters with significant physiological relevance that can serve as biomarkers for patient classification. Results show that the model can reproduce a spectrum of blood pressure responses successfully, fitting the trajectory displayed by the experimental data. The controller exhibits behavior that emulates the operation of the sympathetic system. These encouraging findings underscore the potential of computational methods in evaluating pathologies associated with autonomic nervous system control, warranting further exploration and novel approaches.