Multiscale Computational Modeling of Myocardial Hemodynamics, Oxygen Transport, and Autoregulation in Health and Disease

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

Project Summary/Abstract Myocardial hemodynamic function is heavily influenced by intramyocardial pressure which increases during systole and is highest in the subendocardial region. The complex interaction between myocardial tissue and vasculature leads to unique hemodynamic phenomena in the myocardium including vascular compression during systole in the subendocardium, diastolic-dominant arterial blood flow, bouts of retrograde arterial flow during systole, and systolic dominant venous flow. Vasoregulation, adjusting the diameter of blood vessels through the constriction or relaxation of smooth muscle cells in vessel walls, can alter myocardial hemodynamics and help match oxygen delivery to myocardial oxygen demand. Currently, there exist numerous hypotheses regarding how the biomechanics of myocardial hemodynamics and physiological vasoregulatory responses must operate in order to supply sufficient oxygen to all areas of the myocardium. The overall goals of this project are to develop comprehensive computational models of myocardial hemodynamics and oxygen perfusion that incorporates vasoregulatory mechanisms and to use these models to test hypotheses on the mechanisms governing transmural variation of hemodynamics and oxygen perfusion. Key model constituents will include: 1) anatomically realistic arterial, capillary, and venous networks; 2) temporally varying inlet arterial pressure and temporally and spatially varying transmural pressures; 3) high- fidelity oxygen transport at the capillary scale. Models will be identified and validated based on data from in vivo and in vitro experiments through an ongoing collaboration between research groups at the University of Michigan and University of North Texas. The integrated model, in turn, will be used to analyze results, make novel predictions, develop and refine new hypotheses, and design new experiments.