The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile—with emphasis on velocity acceleration—to endothelial function and vascular tone. 1. Introduction The pathological complications of atherosclerosis, namely, heart attacks and strokes, remain the leading cause of mortality in the Western world [1]. Preceding atherosclerosis is endothelial dysfunction [2–4]. The flow-mediated dilation (FMD) test has emerged as the noninvasive standard for assessing in vivo endothelial function [5]. Despite its potential, the validity of the FMD test has been questioned due to the lack of normalization to the primary stimulus, shear stress [6–10]. Fortunately, the ultrasound technology used to conduct the FMD test can also provide estimates of shear stress [11]. Typically, shear stress is estimated by employing a simplified mathematical model based on Poiseuille’s law. More sophisticated approaches using magnetic resonance imaging are available, but are beyond the reach of most clinical studies since such techniques are not readily available, are too expensive, and are technically challenging and time consuming [12–14]. Little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady shear component. In vitro studies suggest that these two distinct fluid stimuli regulate short- and long-term endothelial function via independent biomechanical pathways [15–17]. The parameter typically incorporated into the Poiseuille’s law equation for shear stress is time-averaged blood velocity, that is, blood velocity averaged across the
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