Developing a Technique to Create a Uniform, Targeted, Transient Shear Stress Stimulus to Assess Endothelial Function

Abstract

The lining (endothelium) of blood vessels regulates vessel health and diameter. Blood flow-associated shear stress (frictional force) imparted on the endothelium stimulates vasodilation (flow-mediated dilation, FMD). FMD as an index of endothelial function is stimulated by an uncontrolled increase in shear stress created with limb occlusion release [reactive hyperemia (RH)-FMD]. RH-FMD interpretation is complicated because differences in RH-FMD between groups/conditions may reflect stimulus magnitude variability rather than distinct endothelial function. Moreover, smaller diameter arteries tend to have larger FMD responses and it is unclear whether this can be attributed to a larger stimulus or other factors related to artery size. The purpose of this thesis was to develop a controlled, targeted, transient RH (CTRH) shear stress stimulus and to compare CTRH-FMD to standard RH-FMD. We hypothesized that the CTRH test would reduce stimulus and FMD response variability and eliminate any relationships between artery size, shear stress, and FMD. Twenty-one healthy adults (ages 22 ± 3) participated in two visits each involving three trials of the RH or CTRH test. The CTRH test incorporated three minutes of handgrip exercise during the occlusion to create a large RH “reserve”. During 40s of cuff release, RH in the brachial artery of the arm was controlled at a target shear stress of 120s-1 by pressing on the vessel at the inside of the elbow. The CTRH test reduced stimulus variability compared to the RH test [within-subject coefficient of variation (CV) CTRH: 3.4 ± 2.3% vs. RH: 8.9 ± 4.6%; p < 0.001] , while FMD response variability remained unchanged (within-subject CV CTRH: 28.9 ± 17.9% vs. RH: 26.8 ± 26.6%; p = 0.350). Although smaller arteries experienced a larger stimulus in the RH test (r2 = 0.27; p = 0.0181), there was an unexpected positive relationship between artery size and FMD (r2 = 0.22; p = 0.0451). The artery size-FMD relationship in the CTRH test was eliminated, however, the importance of stimulus control to this elimination is unclear. We demonstrated that a transient shear stress stimulus can be controlled and targeted. Future research is needed to assess the utility of CTRH-FMD for investigations of vascular function and health in a wider population.