Previous studies have demonstrated that coronary microvessels are regulated by at least three possible means: metabolite-induced, shear-induced, and pressure-induced (myogenic) mechanisms. Adenosine, a putative metabolic vasodilator, preferentially dilates downstream coronary microvessels, whereas the shear-sensitive mechanism is detected predominantly in upstream larger microvessels. However, the interaction of these mechanisms and the significance of the heterogeneous vascular responsiveness in flow regulation have not been evaluated. These tasks cannot be performed experimentally because of several confounding factors that cannot be separated. Therefore, the present study employed a data-based modeling approach to investigate the role of response heterogeneity in a coronary vascular network and to test the hypothesis that shear-sensitive mechanism or the myogenic mechanisms will enhance the vascular sensitivity to adenosine due to the heterogeneity of the vascular responsiveness. We obtained necessary data and developed empirical models for the responsiveness of single vessels to pressure, shear stress, and adenosine. With the single-vessel models, a network model was established based on the branching pattern of coronary microvessels, mass balance, and fluid mechanics laws. Model simulation predicted an enhanced vascular response to adenosine in the network. Such an enhancement is caused by the heterogeneous vascular response to adenosine and the predominant flow-induced dilation in the large arterioles. Preferential dilation of the downstream small arterioles to adenosine initiates an increase in flow and a decrease in pressure at upstream vessels. The increased flow activates the shear-sensitive mechanism of the upstream large arterioles and further enhances the flow. This hemodynamic interaction contributes up to approximately 20% of the adenosine-induced flow increase and also reduces the adenosine-induced pressure drop. In contrast to the shear-sensitive mechanism, myogenic response contributes relatively little to the vascular response to adenosine. These results suggest that various vascular regulation mechanisms and the response heterogeneity of vessels of different sizes may act in an integrative fashion for the optimal control of microvascular perfusion.

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The dynamics of the coronary system is complicated by its dependence on the mechanical properties of the coronary vessels, the anatomical distribution of the vasculature, the biochemical and neurohormonal regulation, and the effect of myocardial contraction. Several types of coronary system models were proposed, focusing on different aspects of coronary system behavior and supported by different animal experiment methodologies. The lumped models were based on well-controlled coronary pressure-flow measurement and simplified assumptions. They are probably most useful for interpreting hemodynamic data measured in modern catheterizaton labs. Anatomical models, with the advancement in morphometric research, coronary angiography, and video densitometry, provided branching pattern, geometric distribution, and distensibility of coronary vessels. Mathematical description based on vascular waterfall theory, intramyocardial pump model, and time varying elastance concept provided some explanation of the interaction between the coronary system and myocardial contraction. More accurate models would include intramyocardial pressure, microcirculatory hemodynamics, coronary flow regulation, and myocardial oxygen supply and consumption. The combination of different models, may lead to a more comprehensive understanding of the coronary system.

Several lumped models have been proposed to characterize the elastic behavior of the epicardial coronary artery, which are based on well-controlled animal experiments. It is still unclear as to which model is most suitable for analyzing the physiological pressure-flow data for the normal catheterization labs. In this research, different perfusion pressure patterns measured from a mongrel dog were used to drive four mathematical models to investigate the influence of the pressure dependence and viscoelastic effect on epicardial capacitive flow. Results show that the nonlinear behavior of the epicardial capacitance can be approximated with a linear model, and the viscoelastic effect only slightly reduces the amplitude of the protosystolic peak. Further analysis in frequency and time domain revealed the underlying mechanism for the above observation. We conclude that a constant capacitance model can be used to analyze the protosystolic data for estimating the epicardial capacitance.

Coronary angioplasty and pressure tracing records of patients with coronary artery stenosis and subsequent hyperemia conditions were obtained and analyzed. Fractional flow reserve (FFR) was calculated and plotted against percent of area stenosis. Under adenosine-induced hyperemia, FFR decreased. The extent of decrease is determined by the percent of stenosis and the responsiveness of intramural coronary artery.