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

Area of Science:

• Cardiovascular Physiology
• Biomechanical Modeling
• Computational Biology

Background:

• Coronary autoregulation maintains constant myocardial blood flow via complex mechanisms.
• Understanding these coupled mechanisms and their heterogeneity is challenging.
• Existing models often use simplified lumped parameter approaches.

Purpose of the Study:

• To develop a novel, microstructurally-motivated model of coronary autoregulation.
• To simulate autoregulation across different myocardial depths (subepicardium, midwall, subendocardium).
• To investigate the mechanisms of coronary autoregulation and potential for vascular remodeling studies.

Main Methods:

• Developed a model based on constrained mixture theory with anatomical and structural parameters.
• Calibrated the model using a homeostatic optimization framework.
• Extended Womersley's theory to simulate phasic coronary hemodynamics with time-varying intramyocardial pressure.

Main Results:

• The calibrated model accurately reproduced baseline hemodynamics and autoregulatory responses.
• Simulations matched experimentally measured subendocardium-to-subepicardium flow ratios (ENDO/EPI).
• The model demonstrated predictive capability for changes in vessel diameter and epicardial pressure.

Conclusions:

• The microstructurally-motivated framework provides a mechanistic basis for studying coronary autoregulation.
• The model accurately simulates heterogeneous autoregulatory responses in the coronary tree.
• This approach is suitable for investigating long-term vascular growth and remodeling in pathological conditions.