THE ROLE OF FLUID-MECHANICS IN THE LOCALIZATION AND DETECTION OF ATHEROSCLEROSIS

Fluid dynamics research over the past twenty years has contributed immensely to our knowledge of atherosclerosis. The ability to detect localized atherosclerotic plaques using noninvasive ultrasonic methods was advanced significantly by investigations into the nature and occurrence of velocity disturbances created by arterial stenoses, and diagnosis of carotid bifurcation disease using a combination of ultrasonic imaging and Doppler measurement of blood velocity is now quite routine. Since atherosclerotic plaques tend to be localized at sites of branching and artery curvature and since these locations would be expected to harbor complex flow patterns, investigators postulated that fluid dynamics might play an initiating role in atherogenesis. Several fluid dynamic variables were proposed as initiating factors. Investigations were undertaken during the 1980s in which fluid dynamic model experiments with physiologic geometries and flow conditions were employed to simulate arterial flows and in which morphometric mapping of intimal thickness was performed in human arteries. Correlations between fluid dynamic variables and intimal thickness revealed that atherosclerotic plaques tended to occur at sites of low and oscillating wall shear stress, and these observations were reinforced by studies in a monkey model of atherosclerosis. Concomitantly, it was realized that arteries adapt their diameters so as to maintain wall shear stress in a narrow range of values around 15 dynes/cm2, findings which were based both on observations of normal arteries and on animal studies in which flow rates were manipulated and arterial diameter adaptation was measured. Currently, a working hypothesis for the role of fluid dynamics in atherogenesis is that intimal thickening is a normal response to low wall shear stress, and this intimal thickening can develop into an early atherosclerotic plaque under certain circumstances such as excessive low density lipoprotein concentrations in blood.