A microstructurally motivated framework to study autoregulation in the coronary circulation.

Area of Science:

• Cardiovascular Physiology
• Biomedical Engineering
• Computational Biology

Background:

• Coronary autoregulation ensures constant myocardial blood flow despite perfusion pressure changes.
• Mechanisms include myogenic, shear-dependent, and metabolic controls, acting heterogeneously across the coronary tree.
• Previous models struggle to integrate these coupled mechanisms and their spatial variations.

Purpose of the Study:

• To develop a microstructurally motivated computational framework for studying coronary autoregulation.
• To simulate autoregulation across three myocardial depths (subepicardium, midwall, subendocardium).
• To investigate the contributions of different control mechanisms and the impact of microstructural changes.

Main Methods:

• Developed a framework based on constrained mixture theory and non-linear continuum mechanics.
• Constructed coronary trees using a homeostatic optimization approach for morphology and hemodynamics.
• Incorporated passive/active vessel wall properties, autoregulatory stimuli (myogenic, metabolic, shear), and phasic dynamics.

Main Results:

• The framework successfully reproduced experimental autoregulatory responses, transmural flow ratios, and diameter changes.
• Sensitivity analysis identified metabolic mechanisms as the primary drivers of autoregulation, with myogenic response being important.
• Simulations demonstrated how microstructural alterations (e.g., collagen stiffening) impair autoregulatory capacity.

Conclusions:

• The microstructurally motivated framework provides a unified platform for studying coronary autoregulation.
• It offers mechanistic insights into pathophysiological states affecting autoregulatory function.
• This approach facilitates hypothesis testing for both short-term tone regulation and long-term vascular remodeling.