Computer simulated modeling of healthy and diseased right ventricular and pulmonary circulation

We have previously developed a simulated cardiovascular physiology model for in-silico testing and validation of novel closed-loop controllers. To date, a detailed model of the right heart and pulmonary circulation was not needed, as previous controllers were not intended for use in patients with cardiac or pulmonary pathology. With new development of controllers for vasopressors, and looking forward, for combined vasopressor-fluid controllers, modeling of right-sided and pulmonary pathology is now relevant to further in-silico validation, so we aimed to expand our existing simulation platform to include these elements. Our hypothesis was that the completed platform could be tuned and stabilized such that the distributions of a randomized sample of simulated patients’ baseline characteristics would be similar to reported population values. Our secondary outcomes were to further test the system in representing acute right heart failure and pulmonary artery hypertension. After development and tuning of the right-sided circulation, the model was validated against clinical data from multiple previously published articles. The model was considered ‘tuned’ when 100% of generated randomized patients converged to stability (steady, physiologically-plausible compartmental volumes, flows, and pressures) and ‘valid’ when the means for the model data in each health condition were contained within the standard deviations for the published data for the condition. A fully described right heart and pulmonary circulation model including non-linear pressure/volume relationships and pressure dependent flows was created over a 6-month span. The model was successfully tuned such that 100% of simulated patients converged into a steady state within 30 s. Simulation results in the healthy state for central venous volume (3350 ± 132 ml) pulmonary blood volume (405 ± 39 ml), pulmonary artery pressures (systolic 20.8 ± 4.1 mmHg and diastolic 9.4 ± 1.8 mmHg), left atrial pressure (4.6 ± 0.8 mmHg), PVR (1.0 ± 0.2 wood units), and CI (3.8 ± 0.5 l/min/m2) all met criteria for acceptance of the model, though the standard deviations of LAP and CI were somewhat narrower than published comparators. The simulation results for right ventricular infarction also fell within the published ranges: pulmonary blood volume (727 ± 102 ml), pulmonary arterial pressures (30 ± 4 mmHg systolic, 12 ± 2 mmHg diastolic), left atrial pressure (13 ± 2 mmHg), PVR (1.6 ± 0.3 wood units), and CI (2.0 ± 0.4 l/min/m2) all fell within one standard deviation of the reported population values and vice-versa. In the pulmonary hypertension model, pulmonary blood volume of 615 ± 90 ml, pulmonary arterial pressures of 80 ± 14 mmHg systolic, 36 ± 7 mmHg diastolic, and the left atrial pressure of 11 ± 2 mmHg all met criteria for acceptance. For CI, the simulated value of 2.8 ± 0.4 l/min/m2 once again had a narrower spread than most of the published data, but fell inside of the SD of all published data, and the PVR value of 7.5 ± 1.6 wood units fell in the middle of the four published studies. The right-ventricular and pulmonary circulation simulation appears to be a reasonable approximation of the right-sided circulation for healthy physiology as well as the pathologic conditions tested.