Effects of Unilateral Arm Warming or Cooling on the Modulation of Brachial Artery Shear Stress and Endothelial Function during Leg Exercise in Humans

Acute heat exposure protects against endothelial ischemia-reperfusion (I/R) injury in humans. However, the mechanism/s mediating this protective effect remain unclear. We tested the hypothesis that inhibiting the increase in shear stress induced by acute heat exposure would attenuate the protection of endothelial function following I/R injury. Nine (3 women) young healthy participants were studied under 3 experimental conditions: 1) thermoneutral control; 2) whole-body heat exposure to increase body core temperature by 1.2 °C; 3) heat exposure + brachial artery compression to inhibit the temperature-dependent increase in shear stress. Endothelial function was assessed via brachial artery flow-mediated dilatation before (pre-I/R) and after (post-I/R) 20 min of arm ischemia followed by 20 min of reperfusion. Brachial artery shear rate was increased during heat exposure (681 ± 359 s-1), but not for thermoneutral control (140 ± 63 s-1; P < 0.01 vs. heat exposure) nor heat + brachial artery compression (139 ± 60 s-1; P < 0.01 vs. heat exposure). Ischemia-reperfusion injury reduced flow-mediated dilatation following thermoneutral control (pre-I/R, 5.5 ± 2.9 % vs. post-I/R, 3.8 ± 2.9 %; P = 0.06), but was protected following heat exposure (pre-I/R, 5.8 ± 2.9 % vs. post-I/R, 6.1 ± 2.9 %; P = 0.5) and heat + arterial compression (pre-I/R, 4.4 ± 2.8 % vs. post-I/R, 5.8 ± 2.8 %; P = 0.1). Contrary to our hypothesis, our findings demonstrate that shear stress induced by acute heat exposure is not obligatory to protect against endothelial I/R injury in humans.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.01065.2018 ◽

2019 ◽

Vol 126 (5) ◽

pp. 1335-1342 ◽

Cited By ~ 8

Author(s):

Joshua C. Tremblay ◽

Arman S. Grewal ◽

Kyra E. Pyke

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Endothelial Function ◽

Brachial Artery ◽

Duplex Ultrasound ◽

Flow Mediated Dilation ◽

Relative Contribution ◽

Stress Components ◽

Retrograde Shear

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.

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Fluctuation in shear rate, with unaltered mean shear rate, improves brachial artery flow-mediated dilation in healthy, young men

Journal of Applied Physiology ◽

10.1152/japplphysiol.00009.2019 ◽

2019 ◽

Vol 126 (6) ◽

pp. 1687-1693 ◽

Cited By ~ 4

Author(s):

Sophie M. Holder ◽

Ellen A. Dawson ◽

Áine Brislane ◽

Jonny Hisdal ◽

Daniel J. Green ◽

...

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Endothelial Function ◽

Brachial Artery ◽

Negative Pressure ◽

Mixed Model ◽

Linear Mixed Model ◽

Flow Mediated Dilation ◽

Conduit Artery ◽

Artery Flow

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.

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Endothelial dysfunction in workers in underground mining of chrome ores

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-11-914-919 ◽

2019 ◽

pp. 914-919

Author(s):

N. V. Zaitseva ◽

A. E. Nosov ◽

Ju. A. Ivashova ◽

A. S. Baidina ◽

V. G. Kostarev

Keyword(s):

Shear Stress ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Working Conditions ◽

Brachial Artery ◽

Comparison Group ◽

Underground Mining ◽

Relative Increase ◽

Observation Group ◽

Brachial Artery Diameter

Introduction. Currently, endothelial dysfunction is considered as one of the initial stages of the pathogenesis of cardiovascular diseases. By isolating a number of biologically active compounds, the endothelium helps to maintain vascular tone and physiological rheology of the blood. Modern production of chrome ore is characterized by a variety of harmful occupational factors (chromium, dust, noise, vibration, severity and intensity of work, cooling microclimate), which can disrupt the normal functioning of the vascular endothelium and lead to the development of cardiovascular diseases.The aim of the study was to study the features of endothelial function in workers engaged in underground mining of chrome ore in harmful working conditions.Materials and methods. The study included 98 miners of the enterprise for the extraction of chrome ore. The comparison group (working in conditions outside the influence of the studied production factors) consisted of 75 employees-managers and specialists of administrative and managerial personnel of the enterprise, comparable in age and experience with the observation group. To assess the vasomotor function of the endothelium, a flow-dependent (endothelium-dependent) vasodilation test was performed using the D. S. Celermajer technique. Post-occlusive increase in brachial artery diameter, brachial artery sensitivity coefficient to endothelial shift change were evaluated.Results. The endothelial function of mine workers did not differ significantly from the comparison group with work experience up to 10 years (the values of the relative increase in the diameter of the brachial artery 12.2% in the observation group and in the comparison group 12.6%, p=0.74). With experience of more than 10 years, the value of the relative increase in the diameter of the brachial artery in the observation group with experience of more than 10 years corresponded to the signs of endothelial dysfunction and amounted to 8.6%, while in the comparison group this figure was 12.4%, which corresponded to normal endothelial function (p=0.019). Endothelial function progressively deteriorated with increasing seniority in mine workers. Conclusions. For workers engaged in underground mining of chrome ore for more than 10 years, a reduced vasodilation reaction to reperfusion after an occlusion test and a low coefficient of sensitivity of the endothelium to shear stress are characteristic. There was no statistically significant decrease in increase in brachial artery diameter and the coefficient of sensitivity of endothelium to shear stress relative to the comparison group was selected only from persons with experience more than 10 years. The comparative analysis of the results of the evaluation of the functional activity of the endothelium in workers of the compared groups indicates that the change in the functional state of the endothelium in miners is associated not only with age, but also with working conditions. The revealed changes predispose to the development of cardiovascular pathology associated with atherosclerosis in workers of underground chrome ore mining.

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Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study

Diabetes and Vascular Disease Research ◽

10.1177/1479164119883540 ◽

2019 ◽

Vol 17 (1) ◽

pp. 147916411988354 ◽

Cited By ~ 2

Author(s):

Concetta Irace ◽

Antonio Cutruzzolà ◽

Martina Parise ◽

Raffaella Fiorentino ◽

Marco Frazzetto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Shear Stress ◽

Endothelial Function ◽

Brachial Artery ◽

Therapy Group ◽

Glycated Haemoglobin ◽

Flow Mediated Dilation ◽

Endothelial Surface ◽

Significant Difference

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect.

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Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide

Clinical Science ◽

10.1042/cs1010629 ◽

2001 ◽

Vol 101 (6) ◽

pp. 629-635 ◽

Cited By ~ 180

Author(s):

Sagar N. DOSHI ◽

Katerina K. NAKA ◽

Nicola PAYNE ◽

Christopher J.H. JONES ◽

Moira ASHTON ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Function ◽

Brachial Artery ◽

Peak Flow ◽

Ultrasound Probe ◽

Upper Arm ◽

Flow Mediated Dilatation ◽

Synthase Inhibitor ◽

Increased Blood Flow ◽

Similar Peak

Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62±3.17%; wrist, 7.25±2.49%; P = 0.003). During l-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25±2.49% to 0.16±2.24%; P < 0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62±3.17% to 7.51±2.34%; P = 0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. l-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

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Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.4.1516 ◽

1996 ◽

Vol 81 (4) ◽

pp. 1516-1521 ◽

Cited By ~ 50

Author(s):

J. K. Shoemaker ◽

H. L. Naylor ◽

Z. I. Pozeg ◽

R. L. Hughson

Keyword(s):

Blood Flow ◽

Brachial Artery ◽

Time Course ◽

Forearm Blood Flow ◽

Voluntary Contraction ◽

Double Blind ◽

Rate Of Increase ◽

Forearm Exercise ◽

Blind Manner ◽

Exercise In Humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

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Determinants of short-term variation in arterial flow-mediated dilatation in healthy young men

Clinical Science ◽

10.1042/cs20050333 ◽

2006 ◽

Vol 110 (4) ◽

pp. 475-482 ◽

Cited By ~ 28

Author(s):

Mikko J. Järvisalo ◽

Laura Jartti ◽

Jukka Marniemi ◽

Tapani Rönnemaa ◽

Jorma S. A. Viikari ◽

...

Keyword(s):

Endothelial Function ◽

Brachial Artery ◽

Serum Insulin ◽

Circadian Variation ◽

Low Fat ◽

Ultrasound Technique ◽

Brachial Artery Diameter ◽

Flow Mediated Dilatation ◽

Hourly Variation ◽

Fat Meal

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

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Are the dynamic response characteristics of brachial artery flow-mediated dilation sensitive to the magnitude of increase in shear stimulus?

Journal of Applied Physiology ◽

10.1152/japplphysiol.01190.2007 ◽

2008 ◽

Vol 105 (1) ◽

pp. 282-292 ◽

Cited By ~ 50

Author(s):

K. E. Pyke ◽

J. A. Hartnett ◽

M. E. Tschakovsky

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Dynamic Response ◽

Phase I ◽

Brachial Artery ◽

Flow Mediated Dilation ◽

Final Phase ◽

Stimulus Magnitude ◽

Brachial Artery Diameter ◽

Response Characteristics

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.

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