Development of a Simplified Multi-Physics Computational Model of the Coronary Microcirculation

Coronary blood flow (CBF) is influenced by multiple biophysical factors, including vascular function (vasoconstriction/vasodilation), structural remodeling (vascular wall thickening), tissue mechanical properties (stiffness), cardiac electrophysiology, and dynamic extravascular forces. However, it is difficult to experimentally determine how these biophysical factors interact to regulate CBF. For example, during type 2 diabetes (T2D) reduced vascular wall stiffness due to reduced coronary vascular smooth muscle cell (VSMC) stiffness, increased wall thickness due to inward hypertrophic remodeling and increased myocardial stiffness may alter CBF. However, the relative importance of these biophysical factors and their direct effect on CBF is not known. Here, we developed a simplified multi-physics computational model of myocardial tissue deformation and intramyocardial blood flow and used this model to investigate how several biophysical factors influence CBF. This model accounts for excitation-contraction coupling, myocardial fiber structure, dynamic myocardial contraction, passive myocardial mechanical properties, and the mechanics of VSMCs in the coronary microvascular walls. Baseline models yielded CBF velocity waveforms that exhibited peak diastolic velocities and waveform morphologies that were comparable to Doppler echocardiography measurements in normal adult humans. Parameter variation studies were conducted to investigate how several biophysical factors alter the morphological properties of the CBF velocity waveform, and results indicate that VSMC and passive myocardial tissue stiffness were the major drivers of CBF. In addition, the flow regulatory properties of VSMCs were found to depend on the degree of myocardial stiffness. This computational framework represents a new way to investigate how coronary-cardiac interactions regulate CBF.