INTERACTION BETWEEN ADENOSINE AND FLOW-INDUCED DILATION IN CORONARY MICROVASCULAR NETWORK

Previous studies have demonstrated that coronary microvessels are regu lated by at least three possible means: metabolite-induced, shear-indu ced, and pressure-induced (myogenic) mechanisms. Adenosine, a putative metabolic vasodilator, preferentially dilates downstream coronary mic rovessels, whereas the shear-sensitive mechanism is detected predomina ntly in upstream larger microvessels. However, the interaction of thes e mechanisms and the significance of the heterogeneous vascular respon siveness in flow regulation have not been evaluated. These tasks canno t be performed experimentally because of several confounding factors t hat cannot be separated. Therefore, the present study employed a data- based modeling approach to investigate the role of response heterogene ity in a coronary vascular network and to test the hypothesis that she ar-sensitive mechanism or the myogenic mechanisms will enhance the vas cular sensitivity to adenosine due to the heterogeneity of the vascula r responsiveness. We obtained necessary data and developed empirical m odels for the responsiveness of single vessels to pressure, shear stre ss, and adenosine. With the single-vessel models, a network model was established based on the branching pattern of coronary microvessels, m ass balance, and fluid mechanics laws. Model simulation predicted an e nhanced vascular response to adenosine in the network. Such an enhance ment is caused by the heterogeneous vascular response to adenosine and the predominant flow-induced dilation in the large arterioles. Prefer ential dilation of the downstream small arterioles to adenosine initia tes an increase in flow and a decrease in pressure at upstream vessels . The increased flow activates the shear-sensitive mechanism of the up stream large arterioles and further enhances the flow This hemodynamic interaction contributes up to similar to 20% of the adenosine-induced flow increase and also reduces the adenosine-induced pressure drop. I n contrast to the shear-sensitive mechanism, myogenic response contrib utes relatively little to the vascular response to adenosine. These re sults suggest that various vascular regulation mechanisms and the resp onse heterogeneity of vessels of different sizes may act in an integra tive fashion for the optimal control of microvascular perfusion.