A Microstructurally-Motivated Framework to Study Autoregulation in the Coronary Circulation
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Coronary autoregulation is the vasculature's short-term ability to maintain steady blood flow across a wide range of perfusion pressures for a given metabolic state. This is achieved through vessel diameter modulation, governed by myogenic, metabolic, and shear-dependent control mechanisms that control smooth muscle cell tone [1]. Investigating coronary autoregulation is challenging due to its heterogeneous nature throughout the coronary circulation. While lumped-parameter models provide valuable insights, their 0D nature limits physical interpretation and mechanistic understanding. To address these limitations, we developed a novel structurally-motivated coronary tree model using constrained mixture theory [2]. Our model was constructed in three stages: (1) calibrating the vessel wall constitutive model using passive and myogenic pressure-diameter data from multiple vessel sizes, (2) using a homeostatic optimization approach to determine coronary tree morphometry at three myocardial depths (subepi, midwall, subendo), and (3) tuning metabolic and shear-dependent control to match the flow-pressure relationship. Flow and pressure waveforms throughout the trees were modeled by Womersley's 1D theory, considering intramyocardial pressures. The resulting model contains three coronary trees endowed with passive and active mechanical properties that replicate reported hemodynamic and autoregulation data. The homeostatic optimization framework produced morphometries with hemodynamic distributions agreeing with literature, and exhibit reported transmural variabilities such as thicker subepi walls and greater subendo diastolic circumferential stress. Model utility was validated against held-out experimental datasets: vessel diameter responses to perfusion pressure drops and transmural flow distribution at varying pressures. Good agreement was achieved in each case, indicating successful capture of short-term coronary adaptations. Simulated flow waveforms also exhibit characteristic in-vivo features, including diastolically dominated large-vessel flow and greater pulsatility in subendo versus subepi vessels. In conclusion, this structurally-motivated model captures key coronary autoregulatory physiology and provides a foundation for studying long-term vascular remodeling in disease.
