A Microstructurally-Motivated Framework to Study Autoregulation in the Coronary Circulation

Coronary autoregulation maintains relatively constant myocardial flow over a wide range of perfusion pressures through myogenic, shear-dependent, and metabolic control mechanisms. Understanding this phenomenon is challenging due to the coupled nature of these mechanisms and their heterogeneous effects throughout the coronary tree. In this study we developed a novel microstructurally-motivated model of coronary autoregulation based on constrained mixture theory, with anatomical and structural parameters calibrated through a homeostatic optimization framework. Autoregulation was simulated at three myocardial depths (subepicardium, midwall, and subendocardium), with the calibrated model accurately reproducing baseline hemodynamics and autoregulatory responses. For changes in epicardial pressure, our model reproduced experimentally measured subendocardium-to-subepicardium flow ratios (ENDO/EPI) and changes in vessel diameter, demonstrating its predictive capability. Furthermore, we extended Womersley's theory to simulate phasic coronary hemodynamics with a time-varying intramyocardial pressure. This microstructurally-motivated framework provides a mechanistic foundation for investigating coronary autoregulation and long-term vascular growth and remodeling in pathphysiological conditions.