Using a Human Circulation Mathematical Model to Simulate the Effects of Hemodialysis and Therapeutic Hypothermia

Background: We developed a hemodynamic mathematical model of human circulation coupled to a virtual hemodialyzer. The model was used to explore mechanisms underlying our clinical observations involving hemodialysis. Methods: The model consists of whole body human circulation, baroreflex feedback control, and a hemodialyzer. Four model populations encompassing baseline, dialysed, therapeutic hypothermia treated, and simultaneous dialysed with hypothermia were generated. In all populations atrial fibrillation and renal failure as co-morbidities, and exercise as a treatment were simulated. Clinically relevant measurables were used to quantify the effects of each in silico experiment. Sensitivity analysis was used to uncover the most relevant parameters. Results: Relative to baseline, the modelled dialysis increased the population mean diastolic blood pressure by 5%, large vessel wall shear stress by 6%, and heart rate by 20%. Therapeutic hypothermia increased systolic blood pressure by 3%, reduced large vessel shear stress by 15%, and did not affect heart rate. Therapeutic hypothermia reduced wall shear stress by 15% in the aorta and 6% in the kidneys, suggesting a potential anti-inflammatory benefit. Therapeutic hypothermia reduced cardiac output under atrial fibrillation by 12% and under renal failure by 20%. Therapeutic hypothermia and exercise did not affect dialyser function, but increased water removal by approximately 40%. Conclusions: This study illuminates some mechanisms of the action of therapeutic hypothermia. It also suggests clinical measurables that may be used as surrogates to diagnose underlying diseases such as atrial fibrillation.