Impact of repeated increases in shear stress via reactive hyperemia and handgrip exercise: no evidence of systematic changes in brachial artery FMD

Abstract

Reactive hyperemia (RH) creates an uncontrolled, transient increase in brachial artery (BA) shear stress (SS) for flow-mediated dilation (FMD) assessment. In contrast, handgrip exercise (HGEX) can create similar, sustained SS increases over repeated trials. The purpose of this study was to examine the impact of repeated SS elevation via RH or HGEX and the relationship between RH and HGEX %FMD. BA diameter and blood velocity were assessed with echo and Doppler ultrasound in 20 healthy subjects. Visit A consisted of four 6-min HGEX trials (HGEX trials 1-4) at the intensity required to achieve a shear rate (SR = mean blood velocity/BA diameter; an estimate of SS) of 65 s(-1). Visit B consisted of four RH trials (RH trials 1-4). The RH SR area under the curve (AUC) was higher in trial 1 versus trial 3 and trial 4 (P = 0.019 and 0.047). The HGEX mean SR was similar across trials (mean SR = 66.1 ± 5.8 s(-1), P = 0.152). There were no differences in %FMD across trials or tests (RH trial 1: 6.9 ± 3.5%, trial 2: 6.9 ± 2.3%, trial 3: 7.1 ± 3.5%, and trial 4: 7.0 ± 2.8%; HGEX trial 1: 7.3 ± 3.6%, trial 2: 7.0 ± 3.6%, trial 3: 6.5 ± 3.5%, and trial 4: 6.8 ± 2.9%, P = 0.913). No relationship between subject's RH %FMD and HGEX %FMD was detected (r(2) = 0.12, P = 0.137). However, with response normalization, a relationship emerged (RH %FMD/SR AUC vs. HGEX %FMD/mean SR, r(2) = 0.44, P = 0.002). In conclusion, with repeat trials, there were no systematic changes in RH or HGEX %FMD. The relationship between normalized RH and HGEX %FMD suggests that endothelial responses to different SS profiles provide related information regarding endothelial function.

Use of Ultrasound for Non-Invasive Assessment of Flow-Mediated Dilation

“…This is consistent with a recent study by Pyke et al 92) , who similarly found a significant relationship between ischemia-induced FMD and handgrip exercise-induced FMD when the FMD responses were normalized to shear rate. Consideration has to be given to the mechanisms inducing FMD; the mechanisms regulating vascular tone may be dependent on the duration of the shear stimulus 81,116,[118][119][120] , with FMD in response to a sustained shear rate likely being less NO-dependent 121) .…”

“…Emphasis is placed on 'consider' since the FMD test should not be normalized to the shear rate using conventional approaches. A number of studies have attempted to account for the effect of shear stimulus on FMD by evaluating the quotient of FMD and shear, rather than FMD alone, or by using analysis of covariance (ANCOVA), with shear stimulus as the cofactor 34,51,[91][92][93][94] . The techniques described above require use of the general linear model (GLM) for determining statistical probabilities associated with the differences found between groups or experimental treatments; however, when using a GLM, the following assumptions must hold true: 1) there must be at least a moderate correlation between the two variables (i.e., shear and FMD), 2) the relationship between shear and diameter must be linear, 3) the intercept of the regression slope must be zero, 4) variance must be similar between groups, and 5) data must be normally distributed 93,95) .…”

“…A number of laboratories are now able to make semi-automated diameter measurements across the cardiac cycle using edge detection software 35,51,92,[101][102][103][104][105][106] . Studies using edge detection software to estimate FMD have reported intersession coefficients of variation of approximately 11-18% 101,106,107) .…”

Assessment of Endothelial Function Using Ultrasound

“…This is consistent with a recent study by Pyke et al (Pyke & Jazuli 2011), who similarly found a significant relationship between ischemia-induced FMD and handgrip exercise-induced FMD when the FMD responses were normalized to shear rate. Consideration has to be given to the mechanism(s) inducing FMD; the mechanisms regulating vascular tone may be dependent on the duration of the shear stimulus (Frangos & Eskin et al 1985;Macarthur & Kuchan & Jo et al 1994;Frangos & Huang et al 1996;Mullen & Kharbanda et al 2001), with FMD in response to sustained shear rate likely being less NO-dependent (Doshi & Naka et al 2001).…”

“…A number of laboratories, using commercial or custom edge-detection software, are now able to make semi-automated diameter measurements (Woodman & Playford et al 2001;Craiem & Chironi et al 2007;Peretz & Leotta et al 2007;Padilla & Johnson et al 2008;Pyke & Jazuli 2011;Thijssen & Tinken et al 2011). The authors of this chapter, using custom edge-detection software, are able to make thirty diameter measurements per second.…”