Variability of flow-mediated dilation measurements with repetitive reactive hyperemia

We investigated the independent contributions of the peak and continued reactive hyperemia on flow-mediated dilation (FMD). 1) For the duration manipulation experiment (DME), 10 healthy males experienced reactive hyperemia durations of 10 s, 20 s, 30 s, 40 s, 50 s, or full reactive hyperemia (RH). 2) For the peak manipulation experiment (PME), eight healthy males experienced reactive hyperemia trials with three peak shear rate magnitudes (large, medium, and small). Data are means ± SD. For the DME, peak shear rate was not different between trials ( P = 0.326). Shear rate area under the curve (AUC) was P < 0.001. Peak %FMD was dependent on shear rate AUC: 10 s, 2.7 ± 1.3; 20 s, 6.2 ± 1.9; 30 s, 7.9 ± 2.9; 40 s, 8.3 ± 3.2; 50 s, 7.9 ± 3.2; full RH, 9.3 ± 4.1, with 10 and 20 s less than full RH ( P < 0.001). For the PME, peak shear rate was different between trials (large, 1,049.1 ± 285.8; medium, 726.4 ± 228.8; small, 512.8 ± 161.8; P < 0.001). AUC of the continued shear rate was not ( P = 0.412). Peak %FMD was unaffected by peak shear rate (large, 7.0 ± 2.7%; medium, 7.4 ± 2.6%; small, 6.6 ± 1.8%; P = 0.542). Peak and AUC shear stimulus were not significantly related in full RH ( r2 = 0.35, P = 0.07). We conclude that the shear stimulus AUC, not the peak itself, is the critical determinant of the peak FMD response. This indicates AUC as the best method of quantifying reactive hyperemia shear stimulus for %FMD normalization.

Download Full-text

Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00571.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. H119-H126 ◽

Cited By ~ 47

Author(s):

Kyra Pyke ◽

Daniel J. Green ◽

Cara Weisbrod ◽

Matthew Best ◽

Lawrence Dembo ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Shear Rate ◽

Flow Velocity ◽

Radial Artery ◽

Blood Flow Velocity ◽

Reactive Hyperemia ◽

Area Under The Curve ◽

Flow Mediated Dilation ◽

Significant Difference

This study investigated the nitric oxide (NO) dependence of radial artery (RA) flow-mediated dilation (FMD) in response to three different reactive hyperemia (RH) shear stimulus profiles. Ten healthy males underwent the following three RH trials: 1) 5 min occlusion (5 trial), 2) 10 min occlusion (10 trial), and 3) 10 min occlusion with cuff reinflation at 30 s (10–30 trial). Trials were performed during saline infusion and repeated during NG-monomethyl-l-arginine (l-NMMA) infusion in the brachial artery. RA blood flow velocity was measured with Doppler ultrasound, and B-mode RA images were analyzed using automated edge detection software. Shear rate estimation of shear stress was calculated as the blood flow velocity/vessel diameter. l-NMMA decreased baseline vascular conductance by 35%. l-NMMA infusion did not affect the peak shear rate stimulus ( P = 0.681) or the area under the curve (AUC) of shear rate to peak FMD ( P = 0.088). The AUC was significantly larger in the 10 trial vs. the 10–30 or 5 trial ( P < 0.001). Although percent FMD (%change in diameter) in the 10 trial was larger than that in the 5 trial ( P = 0.035), there was no significant difference in %FMD between the saline and l-NMMA conditions in any trial: 5 trial, 5.62 ± 1.48 vs. 5.63 ± 1.27%; 10 trial, 9.07 ± 1.16 vs. 11.22 ± 2.21%; 10–30 trial, 6.52 ± 1.43 vs. 7.98 ± 1.51% for saline and l-NMMA, respectively ( P = 0.158). We conclude the following: 1) RH following 10 min of occlusion results in an enhanced stimulus and %FMD compared with 5 min of occlusion. 2) When the occlusion cuff is reinflated 30 s postrelease of a 10 min occlusion, it does not result in an enhanced %FMD compared with that which results from RH following 5 min of occlusion. 3) The lack of effect of l-NMMA on FMD suggests that NO may not be obligatory for radial artery FMD in response to either 5 or 10 min of occlusion in healthy volunteers.

Download Full-text

Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00314.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. H442-H448 ◽

Cited By ~ 98

Author(s):

Andrew C. Betik ◽

Victoria B. Luckham ◽

Richard L. Hughson

Keyword(s):

Blood Flow ◽

Brachial Artery ◽

Reactive Hyperemia ◽

Flow Mediated Dilation ◽

High Frequency Ultrasound ◽

Upper Arm ◽

Random Measurement Error ◽

Occlusion Cuff ◽

Proximal Occlusion ◽

Forearm Occlusion

Different magnitudes and durations of postocclusion reactive hyperemia were achieved by occluding different volumes of tissue with and without ischemic exercise to test the hypotheses that flow-mediated dilation (FMD) of the brachial artery would depend on the increase in peak flow rate or shear stress and that the position of the occlusion cuff would affect the response. The brachial artery FMD response was observed by high-frequency ultrasound imaging with curve fitting to minimize the effects of random measurement error in eight healthy, young, nonsmoking men. Reactive hyperemia was graded by 5-min occlusion distal to the measurement site at the wrist and the forearm and proximal to the site in the upper arm. Flow was further increased by exercise during occlusion at the wrist and forearm positions. For the two wrist occlusion conditions, flow increased eightfold and FMD was only 1 to 2% ( P > 0.05). After the forearm and upper arm occlusions, blood flow was almost identical but FMD after forearm occlusions was 3.4% ( P < 0.05), whereas it was significantly greater (6.6%, P < 0.05) and more prolonged after proximal occlusion. Forearm occlusion plus exercise caused a greater and more prolonged increase in blood flow, yet FMD (7.0%) was qualitatively and quantitatively similar to that after proximal occlusion. Overall, the magnitude of FMD was significantly correlated with peak forearm blood flow ( r = 0.59, P < 0.001), peak shear rate ( r = 0.49, P < 0.002), and total 5-min reactive hyperemia ( r = 0.52, P < 0.001). The prolonged FMD after upper arm occlusion suggests that the mechanism for FMD differs with occlusion cuff position.

Download Full-text

Noninvasive Assessment of Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery

Vascular Medicine ◽

10.1177/1358863x9700200203 ◽

1997 ◽

Vol 2 (2) ◽

pp. 87-92 ◽

Cited By ~ 128

Author(s):

Akimi Uehata ◽

Eric H Lieberman ◽

Marie D Gerhard ◽

Todd J Anderson ◽

Peter Ganz ◽

...

Keyword(s):

Blood Flow ◽

Endothelial Function ◽

Brachial Artery ◽

Vascular Function ◽

Reactive Hyperemia ◽

Intraobserver Variability ◽

Flow Mediated Dilation ◽

Noninvasive Technique ◽

Brachial Artery Diameter ◽

Cuff Occlusion

Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 ± 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 ± 376%. Five min of cuff occlusion was sufficient to achieve 97 ± 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9 % and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.

Download Full-text

Effect of heat stress on vascular outcomes in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00682.2018 ◽

2019 ◽

Vol 126 (3) ◽

pp. 771-781 ◽

Cited By ~ 5

Author(s):

Jem L. Cheng ◽

Maureen J. MacDonald

Keyword(s):

Disease Burden ◽

Pulse Wave ◽

Reactive Hyperemia ◽

Stiffness Index ◽

Flow Mediated Dilation ◽

Environmental Stressor ◽

Beneficial Effects ◽

Promising Area ◽

At Risk Populations ◽

Cutaneous Vascular Conductance

In addition to its role as an environmental stressor, scientists have recently demonstrated the potential for heat to be a therapy for improving or mitigating declines in arterial health. Many studies at both ends of the scientific controls spectrum (tightly controlled, experimental vs. practical) have demonstrated the beneficial effects of heating on microvascular function (e.g., reactive hyperemia, cutaneous vascular conductance); endothelial function (e.g., flow-mediated dilation); and arterial stiffness (e.g., pulse-wave velocity, compliance, β-stiffness index). It is important to note that findings of beneficial effects are not unanimous, likely owing to the varied methodology in both heating protocols and assessments of outcome measures. Mechanisms of action for the effects of both acute and chronic heating are also understudied. Heat science is a very promising area of human physiology research, as it has the potential to contribute to approaches addressing the global cardiovascular disease burden, particularly in aging and at risk populations, and those for whom exercise is not feasible or recommended.

Download Full-text

Relation of Long-Term Exposure to Air Pollution to Brachial Artery Flow-Mediated Dilation and Reactive Hyperemia

The American Journal of Cardiology ◽

10.1016/j.amjcard.2014.03.048 ◽

2014 ◽

Vol 113 (12) ◽

pp. 2057-2063 ◽

Cited By ~ 35

Author(s):

Elissa H. Wilker ◽

Petter L. Ljungman ◽

Mary B. Rice ◽

Itai Kloog ◽

Joel Schwartz ◽

...

Keyword(s):

Air Pollution ◽

Brachial Artery ◽

Reactive Hyperemia ◽

Flow Mediated Dilation ◽

Artery Flow

Download Full-text

Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes

Hypertension ◽

10.1161/hypertensionaha.120.15721 ◽

2020 ◽

Vol 76 (6) ◽

pp. 1734-1743

Author(s):

Scott T. Chiesa ◽

M. Loredana Marcovecchio ◽

Paul Benitez-Aguirre ◽

Fergus J. Cameron ◽

Maria E. Craig ◽

...

Keyword(s):

Type 1 Diabetes ◽

High Risk ◽

Pulse Wave Velocity ◽

Pulse Wave ◽

Controlled Trial ◽

Reactive Hyperemia ◽

Flow Mediated Dilation ◽

Reactive Hyperemia Index

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0–7.2] versus 5.3% [4.7–5.9]; P =0.005), whereas no effect was observed following statin use (6.2% [5.5–6.8] versus 5.8% [5.1–6.4]; P =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8–5.9] versus 6.3% [5.8–6.7] for high-risk versus low-risk groups; P =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment ( P >0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03–0.12]; P =0.001 and 0.5 m/s [0.4–0.6]; P <0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier NCT01581476.

Download Full-text

Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.01245.2003 ◽

2004 ◽

Vol 97 (2) ◽

pp. 499-508 ◽

Cited By ~ 179

Author(s):

Kyra E. Pyke ◽

Erin M. Dwyer ◽

Michael E. Tschakovsky

Keyword(s):

Shear Stress ◽

Shear Rate ◽

Brachial Artery ◽

Reactive Hyperemia ◽

Flow Mediated Dilation ◽

Response Peak ◽

Dependent Flow ◽

Flow Mediated Vasodilation ◽

The Impact ◽

Forearm Occlusion

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.

Download Full-text

The impact of acute mental stress on brachial artery flow-mediated dilation differs when shear stress is elevated by reactive hyperemia versus handgrip exercise

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0328 ◽

2013 ◽

Vol 38 (5) ◽

pp. 498-506 ◽

Cited By ~ 16

Author(s):

Ingrid C. Szijgyarto ◽

Trevor J. King ◽

Jennifer Ku ◽

Veronica J. Poitras ◽

Brendon J. Gurd ◽

...

Keyword(s):

Shear Stress ◽

Brachial Artery ◽

Mental Stress ◽

Stress Reactivity ◽

Reactive Hyperemia ◽

Blood Velocity ◽

Flow Mediated Dilation ◽

Handgrip Exercise ◽

Stress Task ◽

The Impact

Acute mental stress can impair brachial artery (BA) flow-mediated dilation (FMD) in response to reactive hyperemia (RH) induced increases in shear stress. Handgrip exercise (HGEX) is emerging as a useful tool to increase shear stress for FMD assessment; however, the impact of acute mental stress on HGEX-FMD is unknown. The purpose of this study was to determine whether acute mental stress attenuates RH- and HGEX-induced BA-FMD to a similar extent. In 2 counterbalanced visits, 16 healthy males (19–27 years of age) performed RH-FMD or HGEX-FMD tests after a counting control task (prestress FMD) and a speech and arithmetic stress task (poststress FMD). BA diameter and mean blood velocity were assessed with echo and Doppler ultrasound, respectively. Shear stress was estimated using shear rate (SR = BA blood velocity/BA diameter). Mean arterial pressure (MAP), heart rate (HR), and salivary cortisol were used to assess stress reactivity. Results are expressed as mean ± SE. The stress task elevated MAP (Δ24.0 ± 2.6 mm Hg) and HR (Δ15.5 ± 1.9 beats·min–1), but not cortisol (prestress vs. poststress: 4.4 ± 0.7 nmol·L–1 vs. 4.7 ± 0.7 nmol·L–1; p = 0.625). There was no difference between the pre- and poststress SR stimulus for RH (p = 0.115) or HGEX (p = 0.664). RH-FMD decreased from 5.2% ± 0.6% prestress to 4.1% ± 0.5% poststress (p = 0.071); however, stress did not attenuate HGEX-FMD (prestress vs. poststress: 4.1% ± 0.6% vs. 5.3% ± 0.6%; p = 0.154). The pre- to poststress change in FMD was significantly different in the RH-FMD vs. the HGEX-FMD test (–1.1% ± 0.6% vs. +1.1% ± 0.8%; p = 0.015). In conclusion, acute mental stress appears to have a disparate impact on FMD stimulated by RH vs. HGEX induced increases in shear stress.

Download Full-text