A Constrained Mixture Theory Model to Study Autoregulation in the Coronary Circulation

Abstract

Coronary autoregulation is a short-term response manifested by a relatively constant flow over a wide range of perfusion pressures for a given metabolic state. This phenomenon is thought to be facilitated through a combination of mechanisms, including myogenic, shear dependent, and metabolic controls. The study of coronary autoregulation is challenging due to the coupled nature of the mechanisms and their differential effects through the coronary tree. In this paper, we developed a novel framework to study coronary autoregulation based on the constrained mixture theory. This structurally-motivated autoregulation model required calibration of anatomical and structural parameters of coronary trees via a homeostatic optimization approach using extensive literature data. Autoregulation was then simulated for two different coronary trees: subepicardial and subendocardial. The structurally calibrated model reproduced available baseline hemodynamics and autoregulation data for each coronary tree. The autoregulation analysis showed that the diameter of the intermediate and small arterioles varies the most in response to changes in perfusion pressure. Finally, we demonstrated the utility of the model in two application examples: 1) response to drops in epicardial pressure, and 2) response to drug infusion in the coronary arteries. The proposed structurally-motivated model could be extended to study long-term growth and remodeling in the coronary circulation in response to hypertension, atherosclerosis, etc.