scholarly journals Examining the acute effects of retrograde versus low mean shear rate on flow-mediated dilation

2019 ◽  
Vol 126 (5) ◽  
pp. 1335-1342 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Arman S. Grewal ◽  
Kyra E. Pyke

Arterial endothelial function is acutely and chronically regulated by blood flow-associated shear stress. An acute intervention employing modest forearm cuff occlusion to simultaneously increase retrograde and decrease mean brachial artery shear rate for 30 min evokes transient impairments in flow-mediated dilation (FMD). However, the independent influence of the low mean versus the retrograde shear stress components is unclear. Healthy young adults [ n = 24 (12 women, 12 men); 22 ± 2 yr, body mass index = 25 ± 2 kg/m2 (mean ± SD)] completed three laboratory visits within 1 wk. Visits consisted of 45 min of supine rest followed by a brachial artery FMD test (duplex ultrasound) before and after a 30-min intervention: control (shear rate unchanged), cuff (mean shear rate decreased, retrograde shear rate increased), or arterial compression (mean shear rate decreased, no increase in retrograde shear rate). The mean shear rate on the compression visit was targeted to match that achieved on the cuff visit. Cuff and compression trials decreased mean shear rate to a similar extent (cuff: 43 ± 22 s−1, compression: 43 ± 21 s−1; P = 0.850) compared with control (65 ± 21 s−1; both P < 0.001), with the retrograde component elevated only in the former (cuff: −83 ± 30 s−1, compression: −7 ± 5 s−1; P < 0.001). FMD decreased by 29 ± 30% ( P < 0.001) after the cuff intervention and 32 ± 24% ( P < 0.001) after the compression trial but was unchanged on the control visit (−0.3 ± 18%; P = 0.754). This was not altered by accounting for the shear rate stimulus. An increased retrograde shear stress does not appear to be obligatory for the transient reduction in FMD achieved after a 30-min exposure to low mean shear stress. These findings provide novel mechanistic insight on the regulation of endothelial function in vivo. NEW & NOTEWORTHY Low mean and retrograde shear stress are considered atherogenic; however, their relative contribution to the acute regulation of endothelial function in humans is unclear. Matched reductions in mean shear stress (30 min), with and without increases in retrograde shear stress, elicited equivalent reductions in flow-mediated dilation in men and women. These findings afford novel insight regarding the shear stress components governing the acute (dys)regulation of conduit artery endothelial function in vivo.

2019 ◽  
Vol 126 (6) ◽  
pp. 1687-1693 ◽  
Author(s):  
Sophie M. Holder ◽  
Ellen A. Dawson ◽  
Áine Brislane ◽  
Jonny Hisdal ◽  
Daniel J. Green ◽  
...  

Increase in mean shear stress represents an important and potent hemodynamic stimulus to improve conduit artery endothelial function in humans. No previous study has examined whether fluctuations in shear rate patterns, without altering mean shear stress, impacts conduit artery endothelial function. This study examined the hypothesis that 30-min exposure to fluctuations in shear rate patterns, in the presence of unaltered mean shear rate, improves brachial artery flow-mediated dilation. Fifteen healthy men (27.3 ± 5.0 yr) completed the study. Bilateral brachial artery flow-mediated dilation was assessed before and after unilateral exposure to 30 min of intermittent negative pressure (10 s, −40mmHg; 7 s, 0 mmHg) to induce fluctuation in shear rate, while the contralateral arm was exposed to a resting period. Negative pressure significantly increased shear rate, followed by a decrease in shear rate upon pressure release (both P < 0.001). Across the 30-min intervention, mean shear rate was not different compared with baseline ( P = 0.458). A linear mixed model revealed a significant effect of time observed for flow-mediated dilation ( P = 0.029), with exploratory post hoc analysis showing an increase in the intervention arm (∆FMD +2.0%, P = 0.008), but not in the contralateral control arm (∆FMD +0.5%, P = 0.664). However, there was no effect for arm ( P = 0.619) or interaction effect ( P = 0.096). In conclusion, we found that fluctuations in shear patterns, with unaltered mean shear, improves brachial artery flow-mediated dilation. These novel data suggest that fluctuations in shear pattern, even in the absence of altered mean shear, represent a stimulus to acute change in endothelial function in healthy individuals. NEW & NOTEWORTHY Intermittent negative pressure applied to the forearm induced significant fluctuations in antegrade and retrograde shear rate, while mean shear was preserved relative to baseline. Our exploratory study revealed that brachial artery flow-mediated dilation was significantly improved following 30-min exposure to intermittent negative pressure. Fluctuations in blood flow or shear rate, with unaltered mean shear, may have important implications for vascular health; however, further research is required to identify the underlying mechanisms and potential long-term health benefits.


2008 ◽  
Vol 105 (1) ◽  
pp. 282-292 ◽  
Author(s):  
K. E. Pyke ◽  
J. A. Hartnett ◽  
M. E. Tschakovsky

The purpose of this study was to determine the dynamic characteristics of brachial artery dilation in response to step increases in shear stress [flow-mediated dilation (FMD)]. Brachial artery diameter (BAD) and mean blood velocity (MBV) (Doppler ultrasound) were obtained in 15 healthy subjects. Step increases in MBV at two shear stimulus magnitudes were investigated: large (L; maximal MBV attainable), and small (S; MBV at 50% of the large step). Increase in shear rate (estimate of shear stress: MBV/BAD) was 76.8 ± 15.6 s−1 for L and 41.4 ± 8.7 s−1 for S. The peak %FMD was 14.5 ± 3.8% for L and 5.7 ± 2.1% for S ( P < 0.001). Both the L (all subjects) and the S step trials (12 of 15 subjects) elicited a biphasic diameter response with a fast initial phase (phase I) followed by a slower final phase. Relative contribution of phase I to total FMD when two phases occurred was not sensitive to shear rate magnitude ( r2 = 0.003, slope P = 0.775). Parameters quantifying the dynamics of the FMD response [time delay (TD), time constant (τ)] were also not sensitive to shear rate magnitude for both phases (phase I: TD r2 = 0.03, slope P = 0.376, τ r2 = 0.04, slope P = 0.261; final phase: TD r2 = 0.07, slope P = 0.169, τ r2 = 0.07, slope P = 0.996). These data support the existence of two distinct mechanisms, or sets of mechanisms, in the human conduit artery FMD response that are proportionally sensitive to shear stimulus magnitude and whose dynamic response is not sensitive to shear stimulus magnitude.


2004 ◽  
Vol 287 (1) ◽  
pp. H374-H380 ◽  
Author(s):  
Patricia C. E. de Groot ◽  
Fleur Poelkens ◽  
Miriam Kooijman ◽  
Maria T. E. Hopman

The aim of the study was to assess endothelial function, measured by flow-mediated dilation (FMD), in an inactive extremity (leg) and chronically active extremity (arm) within one subject. Eleven male spinal cord-injured (SCI) individuals and eleven male controls (C) were included. Echo Doppler measurements were performed to measure FMD responses after 10 and 5 min of arterial occlusion of the leg (superficial femoral artery, SFA) and the arm (brachial artery, BA), respectively. A nitroglycerine spray was administered to determine the endothelium independent vasodilatation in the SFA. In the SFA, relative changes in FMD were significantly enhanced in SCI compared with C (SCI: 14.1 ± 1.3%; C: 9.2 ± 2.3%), whereas no differences were found in the BA (SCI: 12.5 ± 2.9%; C: 14.2 ± 3.3%). Because the FMD response is directly proportional to the magnitude of the stimulus, the FMD response was also expressed relative to the shear rate. No differences between the groups were found for the FMD-to-shear rate ratio in the SFA (SCI:0.061 ± 0.023%/s−1; C: 0.049 ± 0.024%/s−1), whereas the FMD-to-shear rate ratio was significantly decreased in the BA of SCI individuals (SCI: 0.037 ± 0.01%/s−1; C: 0.061 ± 0.027%/s−1). The relative dilatory response to nitroglycerine did not differ between the groups. (SCI: 15.6 ± 2.0%; C: 13.4 ± 2.3%). In conclusion, our results indicate that SCI individuals have a preserved endothelial function in the inactive legs and possibly an attenuated endothelial function in the active arms compared with controls.


2012 ◽  
Vol 10 (1) ◽  
Author(s):  
Blair D Johnson ◽  
Kieren J Mather ◽  
Sean C Newcomer ◽  
Timothy D Mickleborough ◽  
Janet P Wallace

2014 ◽  
Vol 39 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Ingrid C. Szijgyarto ◽  
Veronica J. Poitras ◽  
Brendon J. Gurd ◽  
Kyra E. Pyke

Exercise elevates conduit artery shear stress and stimulates flow-mediated dilation (FMD). However, little is known regarding the impact of acute psychological and physical stress on this response. The purpose of this study was to examine the impact of the Trier Social Stress Test (TSST (speech and arithmetic tasks)) and a cold pressor test (CPT) with and without social evaluation (SE) on exercise-induced brachial artery FMD (EX-FMD). A total of 59 healthy male subjects were randomly assigned to 1 of 3 conditions: TSST, CPT, or CPT with SE. During 6 min of handgrip exercise, brachial artery EX-FMD was assessed before and 15 and 35 min poststress with echo and Doppler ultrasound. Shear stress was estimated as shear rate, calculated as brachial artery mean blood velocity/brachial artery diameter. Results are means ± SD. All conditions elicited significant physiological stress responses. Salivary cortisol increased from 4.6 ± 2.4 nmol/L to 10.0 ± 5.0 nmol/L (p < 0.001; condition effect: p = 0.292). Mean arterial pressure increased from 98.6 ± 12.1 mm Hg to 131.9 ± 18.7 mm Hg (p < 0.001; condition effect: p = 0.664). Exercise shear rate did not differ between conditions (p = 0.592), although it was modestly lower poststress (prestress: 72.3 ± 4.5 s−1; 15 min poststress: 70.8 ± 5.4 s−1; 35 min poststress: 70.6 ± 6.1 s−1; trial effect: p = 0.011). EX-FMD increased from prestress to 15 min poststress in all conditions (prestress: 6.2% ± 2.8%; 15 min poststress: 7.9% ± 3.2%; 35 min poststress: 6.6% ± 2.9%; trial effect: p < 0.001; condition effect: p = 0.611). In conclusion, all conditions elicited similar stress responses that transiently enhanced EX-FMD. This response may help to support muscle perfusion during stress.


2017 ◽  
Vol 39 (5) ◽  
pp. 849-858 ◽  
Author(s):  
Kurt J Smith ◽  
Ryan L Hoiland ◽  
Ryan Grove ◽  
Hamish McKirdy ◽  
Louise Naylor ◽  
...  

The mechanistic role of arterial shear stress in the regulation of cerebrovascular responses to physiological stimuli (exercise and hypercapnia) is poorly understood. We hypothesised that, if shear stress is a key regulator of arterial dilation, then matched increases in shear, induced by distinct physiological stimuli, would trigger similar dilation of the large extra-cranial arteries. Participants ( n = 10) participated in three 30-min experimental interventions, each separated by ≥48 h: (1) mild-hypercapnia (FICO2:∼0.045); (2) submaximal cycling (EX; 60%HRreserve); or (3) resting (time-matched control, CTRL). Blood flow, diameter, and shear rate were assessed (via Duplex ultrasound) in the internal carotid and vertebral arteries (ICA, VA) at baseline, during and following the interventions. Hypercapnia and EX produced similar elevations in blood flow and shear rate through the ICA and VA ( p < 0.001), which were both greater than CTRL. Vasodilation of ICA and VA diameter in response to hypercapnia (5.3 ± 0.8 and 4.4 ± 2.0%) and EX (4.7 ± 0.7 and 4.7 ± 2.2%) were similar, and greater than CTRL ( p < 0.001). Our findings indicate that matched levels of shear, irrespective of their driving stimulus, induce similar extra-cranial artery dilation. We demonstrate, for the first time in humans, an important mechanistic role for the endothelium in regulating cerebrovascular response to common physiological stimuli in vivo.


2005 ◽  
Vol 98 (6) ◽  
pp. 2185-2190 ◽  
Author(s):  
M. Rakobowchuk ◽  
C. L. McGowan ◽  
P. C. de Groot ◽  
J. W. Hartman ◽  
S. M. Phillips ◽  
...  

Given the increasing emphasis on performance of resistance exercise as an essential component of health, we evaluated, using a prospective longitudinal design, the potential for resistance training to affect arterial endothelial function. Twenty-eight men (23 ± 3.9 yr old; mean ± SE) engaged in 12 wk of whole body resistance training five times per week using a repeating split-body 3-day cycle. Brachial endothelial function was measured using occlusion cuff-induced flow-mediated dilation. After occlusion of the forearm for 4.5 min, brachial artery dilation and postocclusion blood flow was measured continuously for 15 and 70 s, respectively. Peak and 10-s postocclusion blood flow, shear rate, and brachial artery flow-mediated dilation (relative and normalized to shear rate) were measured pretraining (Pre), at 6 wk of training (Mid), and at 13 wk of training (Post). Results indicated an increase of mean brachial artery diameter by Mid and Post vs. Pre. Peak and 10-s postocclusion blood flow increased by Mid and remained elevated at Post; however, shear rates were not different at any time point. Relative and normalized flow-mediated dilation was also not different at any time point. This study is the first to show that peripheral arterial remodeling does occur with resistance training in healthy young men. In addition, the increase in postocclusion blood flow may indicate improved resistance vessel function. However, unlike studies involving endurance training, flow-mediated dilation did not increase with resistance training. Thus arterial adaptations with high-pressure loads, such as those experienced during resistance exercise, may be quite different compared with endurance training.


2018 ◽  
Vol 315 (6) ◽  
pp. H1532-H1543 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Ryan L. Hoiland ◽  
Howard H. Carter ◽  
Connor A. Howe ◽  
Mike Stembridge ◽  
...  

The study of conduit artery endothelial adaptation to hypoxia has been restricted to the brachial artery, and comparisons with highlanders have been confounded by differences in altitude exposure, exercise, and unknown levels of blood viscosity. To address these gaps, we tested the hypothesis that lowlanders, but not Sherpa, would demonstrate decreased mean shear stress and increased retrograde shear stress and subsequently reduced flow-mediated dilation (FMD) in the upper and lower limb conduit arteries on ascent to 5,050 m. Healthy lowlanders (means ± SD, n = 22, 28 ± 6 yr) and Sherpa ( n = 12, 34 ± 11 yr) ascended over 10 days, with measurements taken on nontrekking days at 1,400 m (baseline), 3,440 m ( day 4), 4,371 m ( day 7), and 5,050 m ( day 10). Arterial blood gases, blood viscosity, shear stress, and FMD [duplex ultrasound of the brachial and superficial femoral arteries (BA and SFA, respectively)] were acquired at each time point. Ascent decreased mean and increased retrograde shear stress in the upper and lower limb of lowlanders and Sherpa. Although BA FMD decreased in lowlanders from 7.1 ± 3.9% to 3.8 ± 2.8% at 5,050 versus 1,400 m ( P < 0.001), SFA FMD was preserved. In Sherpa, neither BA nor SFA FMD were changed upon ascent to 5,050 m. In lowlanders, the ascent-related exercise may favorably influence endothelial function in the active limb (SFA); selective impairment in FMD in the BA in lowlanders is likely mediated via the low mean or high oscillatory baseline shear stress. In contrast, Sherpa presented protected endothelial function, suggesting a potential vascular aspect of high-altitude acclimatization/adaptation. NEW & NOTEWORTHY Upper and lower limb arterial shear stress and flow-mediated dilation (FMD) were assessed on matched ascent from 1,400 to 5,050 m in lowlanders and Sherpa. A shear stress pattern associated with vascular dysfunction/risk manifested in both limbs of lowlanders and Sherpa. FMD was impaired only in the upper limb of lowlanders. The findings indicate a limb-specific impact of high-altitude trekking on FMD and a vascular basis to acclimatization wherein endothelial function is protected in Sherpa on ascent


2004 ◽  
Vol 97 (2) ◽  
pp. 499-508 ◽  
Author(s):  
Kyra E. Pyke ◽  
Erin M. Dwyer ◽  
Michael E. Tschakovsky

The reactive hyperemia test (RHtest) evokes a transient increase in shear stress as a stimulus for endothelial-dependent flow-mediated vasodilation (EDFMD). We developed a noninvasive method to create controlled elevations in brachial artery (BA) shear rate (SR, estimate of shear stress), controlled hyperemia test (CHtest), and assessed the impact of this vs. the RHtest approach on EDFMD. Eight healthy subjects participated in two trials of each test on 3 separate days. For the CHtest, SR was step increased from 8 to 50 s−1, created by controlled release of BA compression during forearm heating. For the RHtest, transient increases in SR were achieved after 5 min of forearm occlusion. BA diameter and blood flow velocity (ultrasound) were measured upstream of compression and occlusion sites. Both tests elicited significant dilation (RHtest: 6.33 ± 3.12%; CHtest: 3.00 ± 1.05%). The CHtest resulted in 1) reduced between-subject SR and EDFMD variability vs. the RHtest [SR coefficient of variation (CV): 4.9% vs. 36.6%; EDFMD CV: 36.16% vs. 51.80%] and 2) virtual elimination of the impact of BA diameter on the peak EDFMD response (peak EDFMD vs. baseline diameter for RHtest, r2 = 0.64, P < 0.01, vs. CHtest, r2 = 0.14, P < 0.01). Normalization of the RHtest EDFMD response to the magnitude of the SR stimulus eliminated test differences in between-subject response variability. Reductions in trial-to-trial and day-to-day SR variability with the CHtest did not reduce EDFMD variability. Between-subject SR variability contributes to EDFMD variability with the RHtest. SR controls with the CHtest or RHtest response normalization are essential for examining EDFMD between groups differing in baseline arterial diameter.


2008 ◽  
Vol 294 (6) ◽  
pp. H2669-H2679 ◽  
Author(s):  
K. E. Pyke ◽  
V. Poitras ◽  
M. E. Tschakovsky

Exercise elevates shear stress in the supplying conduit artery. Although this is the most relevant physiological stimulus for flow-mediated dilation (FMD), the fluctuating pattern of shear that occurs may influence the shear stress-FMD stimulus response relationship. This study tested the hypothesis that the brachial artery FMD response to a step increase in shear is influenced by the fluctuating characteristics of the stimulus, as evoked by forearm exercise. In 16 healthy subjects, we examined FMD responses to step increases in shear rate in three conditions: stable shear upstream of heat-induced forearm vasodilation (FHStable); fluctuating shear upstream of heat-induced forearm vasodilation and rhythmic forearm cuff inflation/deflation (FHFluctuating); and fluctuating shear upstream of exercise-induced forearm vasodilation (FEStep Increase). The mean increase in shear rate (±SD) was the same in all trials (FHFluctuating: 51.69 ± 15.70 s−1; FHStable: 52.16 ± 14.10 s−1; FEStep Increase: 50.14 ± 13.03 s−1 P = 0.131). However, the FHFluctuating and FEStep Increase trials resulted in a fluctuating shear stress stimulus with rhythmic high and low shear periods that were 96.18 ± 24.54 and 11.80 ± 7.30 s−1, respectively. The initial phase of FMD (phase I) was followed by a second, delayed-onset FMD and was not different between conditions (phase I: FHFluctuating: 5.63 ± 2.15%; FHStable: 5.33 ± 1.85%; FEStep Increase: 5.30 ± 2.03%; end-trial: FHFluctuating: 7.76 ± 3.40%; FHStable: 7.00 ± 3.03%; FEStep Increase: 6.68 ± 3.04%; P = 0.196). Phase I speed also did not differ ( P = 0.685). In conclusion, the endothelium transduced the mean shear when exposed to shear fluctuations created by a typical handgrip protocol. Muscle activation did not alter the FMD response. Forearm exercise may provide a viable technique to investigate brachial artery FMD in humans.


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