In vivo blood velocity parameters that contribute to flow-mediated dilation
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Flow-mediated dilation (FMD) is the auto-regulation of blood vessel size in response to flow-induced increases in shear stress. FMD is governed by the vascular endothelium, an important monolayer which also regulates vascular homeostasis. Tests of FMD offer the potential to predict future cardiovascular disease event. The usefulness of these tests can be improved if FMD is normalized to the shear stimulus. The purpose of study one was to determine the importance of velocity acceleration to FMD. FMD was measured prior to and following induced increases in velocity acceleration. Mean blood velocity was kept constant between conditions. Fourteen physically active, young (26+5 years) male subjects were tested. Blood flow to the forearm was manipulated using progressive local heating and handgrip exercise. Brachial artery blood velocities and diameters were measured using ultrasound. Velocity acceleration was increased by inflating a tourniquet around the forearm to 40 mmHg. Hierarchical linear modeling (HLM) was used to estimate change in diameter with repeated measures of shear rate nested within each subject. The shear rate-diameter slope was used to represent FMD. When velocity acceleration was increased FMD was attenuated by 11% (P = 0.015). The second study assessed whether peak- and time integrated-shear rates independently predict FMD. Eleven physically active, young (2+5 years) male subjects were tested. Each subject was tested under transient and steady-state shear rate conditions. During the transient condition, shear rate was increased using four down-stream ischemic durations (2, 4, 6 & 10 min). During the steady-state condition, shear rate was manipulated using progressive local heating and handgrip exercise. HLM was used to estimate change in diameter with repeated measures of shear rate nested within each subject. When accounting for both time integrated and peak shear rates, FMD did not significantly differ between transient and steady-state conditions (P = 0.067). Collectively, these findings suggest that the velocity profile and the peak shear response contribute to the shear stimulus for FMD.