The hypothesis being tested in this proposal is that the detailed, local variations in mass transfer in blood flow can account for the distribution of atherosclerotic intimal thickening at the carotid and left coronary arteries. Currently there is high interest in the mechanisms of how specific features of local blood flow can affect vascular cell structure and function, leading ultimately to atherosclerotic intimal thickening. While wall shear stress can alter endothelial cell behavior and low and oscillating shear correlates to local intimal thickening, several alternative mechanisms have been hypothesized by which the local mass transfer between the blood and the arterial wall may be the ultimate biochemical mediator of cellular behavior. Until recently, the local convective mass transfer has not been quantified in detail for realistic arterial anatomies. Our preliminary results indicate that the local variations in wall mass transfer correlate with intimal thickening in the carotid sinus as well as does wall shear stress. We propose to determine the magnitude and range of the local variation in wall shear and mass transfer for the realistic anatomies of the carotid and left coronary arteries. Specifically, we propose to: (l) establish the capability of computational methods to quantify the local wall shear and mass transfer between blood and the artery wall with much higher spatial resolution than experimental measurements; (2) determine the statistical correlation between local variations in wall mass transfer and wall shear stress to the morphologic intimal thickness and location of raised plaque at the carotid and left coronary bifurcations; (3) determine the relative importance of differing diffusivities of several candidate atherogenic substances such as 02, ADP, LDL and platelets on the local mass transfer variations in arteries; and (4) examine the influence of branch angle on the wall shear and mass transfer parameters at the carotid and coronary bifurcations. These studies will delineate the relative contribution of mass transfer on the localization of early human lesion development and define the biochemical and mass transfer environment of vascular cells which should be incorporated in future in vitro cellular studies.
