LAUSR

Cardiac-coronary interaction and the effects of its patho-physiological variations on spatial heterogeneity of coronary perfusion and myocardial work are still poorly understood. This hypothesis-generating study predicts spatial heterogeneities in both regional cardiac work and perfusion that offer a new paradigm on the vulnerability of the sub-endocardium to ischemia, particularly at the apex. We propose a mathematical and computational modeling framework to simulate the interaction of left ventricular mechanics, systemic circulation and coronary microcirculation. The computational simulations revealed that the relaxation rate of the myocardium has a significant affect whereas the contractility has a marginal effect on both the magnitude and transmural distribution of coronary perfusion. The ratio of sub-endocardial to sub-epicardial perfusion density (Qendo/Qepi) changed by -12 to +6% from a baseline value of 1.16 when myocardial contractility was varied respectively by +25 and -10%; Qendo/Qepi changed by 37%, when sarcomere relaxation rate was faster, b, increased by 10% from the baseline value. The model predicts axial differences in regional myocardial work and perfusion density across the wall thickness. Regional myofiber work done at the apex is 30-50% lower than at the center region, whereas perfusion density in the apex is lower by only 18% compared to the center. There are large axial differences in coronary flow and myocardial work at the sub-endocardial locations with the highest differences located at the apex region. A mismatch exists between perfusion density and regional work done at the sub-endocardium. This mismatch is speculated to be compensated by coronary autoregulation.