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Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus.

Padilla J, Johnson BD, Newcomer SC, Wilhite DP, Mickleborough TD, Fly AD, Mather KJ, Wallace JP - Cardiovasc Ultrasound (2008)

Bottom Line: The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Kinesiology, Indiana University, Bloomington, IN, USA. jpadilla@indiana.edu

ABSTRACT

Background: Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.

Methods: Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 +/- 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation.

Results: One-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p < 0.0001) across forearm occlusion durations. Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).

Conclusion: Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

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Related in: MedlinePlus

Experimental set-up.
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Figure 1: Experimental set-up.

Mentions: On the vascular session day, subjects were instructed to report to the laboratory between 6:00 and 10:00 am having 1) fasted for 12 h, 2) abstained from caffeine, tobacco products, and vitamin supplements for 12 h, and 3) abstained from exercise for 12 h [1]. Women were studied during days 1–7 of their menstrual cycle to minimize the influence of cyclical changes in female hormones. Subjects were instructed to lie supine in a dark, climate-controlled quiet room (22–24°C), with their right arm extended out laterally. A venous blood draw was performed from the antecubital vein. Samples were collected into 6-mL heparin vacutainer tubes for determination of whole blood viscosity and hematocrit. Each subject underwent an acclimation phase (20 min) to obtain a hemodynamic steady state. Heart rate was continuously monitored using a three-lead ECG. Blood pressures were taken in the left arm with a mercury sphygmomanometer to confirm a steady state. A 5 × 84 cm automatic cuff (E-20 rapid cuff inflator, D.E. Hokanson, Bellevue, WA) was placed around the forearm immediately distal to the olecranon process following established guidelines for assessing FMD [1]. To quantify the magnitude of occlusion-induced ischemia (volume and peak), a dual-wavelength near-infrared spectrometry (NIRS) (ISS, Champaign, IL) probe was positioned over the right extensor digitorum muscle (medial aspect, distally from the cuff). The probe was held in place with an elastic bandage. The forearm oxygen tissue saturation (%StO2) was recorded throughout the study. The ultrasound image of the brachial artery was obtained longitudinally 2–10 cm above the antecubital fossa by 2D high resolution (Terason T3000, Teratech Corporation, Burlington, MA) ultrasound system, using a 5 to 12-MHz multifrequency linear-array transducer. Once a satisfactory image was obtained, the right arm was secured using a custom-designed arm immobilizer and the transducer was stabilized using a clamp (Figure 1). Minor corrections of transducer placement were made to maintain optimal imaging. Doppler velocity was also measured via ultrasound. Doppler flow signals were corrected at an insonation angle of 60° and measurements were performed with the sample volume placed in mid-artery. Ultrasound parameters were not changed during the study. Simultaneous Doppler measurements for blood velocity and 2D ultrasound imaging for diameter were continuously recorded for 30 sec at baseline. The automatic forearm cuff was then inflated to 250 mm Hg and maintained for 1, 2, 3, 4 or 5 min; in a randomized order. Diameter and velocity recordings resumed before cuff deflation and continued for 2 min thereafter. Ultrasound images were recorded at 5 frames/second using Camtasia (TechSmith, Okemos, MI) and converted into an AVI file. R-wave gated frames were not captured exclusively because internal data in our laboratory shows that continuous assessment of diameter at 5 frames/second yields the same FMD results (n = 10; FMD = 7.58 ± 0.9 vs. 7.62 ± 0.9%, p = 0.655; Intraclass correlation coefficient = 0.998, p < 0.0001). The occlusion conditions were applied 10 min apart from each other and baseline measurements were re-established prior to each condition.


Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus.

Padilla J, Johnson BD, Newcomer SC, Wilhite DP, Mickleborough TD, Fly AD, Mather KJ, Wallace JP - Cardiovasc Ultrasound (2008)

Experimental set-up.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2542351&req=5

Figure 1: Experimental set-up.
Mentions: On the vascular session day, subjects were instructed to report to the laboratory between 6:00 and 10:00 am having 1) fasted for 12 h, 2) abstained from caffeine, tobacco products, and vitamin supplements for 12 h, and 3) abstained from exercise for 12 h [1]. Women were studied during days 1–7 of their menstrual cycle to minimize the influence of cyclical changes in female hormones. Subjects were instructed to lie supine in a dark, climate-controlled quiet room (22–24°C), with their right arm extended out laterally. A venous blood draw was performed from the antecubital vein. Samples were collected into 6-mL heparin vacutainer tubes for determination of whole blood viscosity and hematocrit. Each subject underwent an acclimation phase (20 min) to obtain a hemodynamic steady state. Heart rate was continuously monitored using a three-lead ECG. Blood pressures were taken in the left arm with a mercury sphygmomanometer to confirm a steady state. A 5 × 84 cm automatic cuff (E-20 rapid cuff inflator, D.E. Hokanson, Bellevue, WA) was placed around the forearm immediately distal to the olecranon process following established guidelines for assessing FMD [1]. To quantify the magnitude of occlusion-induced ischemia (volume and peak), a dual-wavelength near-infrared spectrometry (NIRS) (ISS, Champaign, IL) probe was positioned over the right extensor digitorum muscle (medial aspect, distally from the cuff). The probe was held in place with an elastic bandage. The forearm oxygen tissue saturation (%StO2) was recorded throughout the study. The ultrasound image of the brachial artery was obtained longitudinally 2–10 cm above the antecubital fossa by 2D high resolution (Terason T3000, Teratech Corporation, Burlington, MA) ultrasound system, using a 5 to 12-MHz multifrequency linear-array transducer. Once a satisfactory image was obtained, the right arm was secured using a custom-designed arm immobilizer and the transducer was stabilized using a clamp (Figure 1). Minor corrections of transducer placement were made to maintain optimal imaging. Doppler velocity was also measured via ultrasound. Doppler flow signals were corrected at an insonation angle of 60° and measurements were performed with the sample volume placed in mid-artery. Ultrasound parameters were not changed during the study. Simultaneous Doppler measurements for blood velocity and 2D ultrasound imaging for diameter were continuously recorded for 30 sec at baseline. The automatic forearm cuff was then inflated to 250 mm Hg and maintained for 1, 2, 3, 4 or 5 min; in a randomized order. Diameter and velocity recordings resumed before cuff deflation and continued for 2 min thereafter. Ultrasound images were recorded at 5 frames/second using Camtasia (TechSmith, Okemos, MI) and converted into an AVI file. R-wave gated frames were not captured exclusively because internal data in our laboratory shows that continuous assessment of diameter at 5 frames/second yields the same FMD results (n = 10; FMD = 7.58 ± 0.9 vs. 7.62 ± 0.9%, p = 0.655; Intraclass correlation coefficient = 0.998, p < 0.0001). The occlusion conditions were applied 10 min apart from each other and baseline measurements were re-established prior to each condition.

Bottom Line: The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Kinesiology, Indiana University, Bloomington, IN, USA. jpadilla@indiana.edu

ABSTRACT

Background: Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.

Methods: Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 +/- 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation.

Results: One-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p < 0.0001) across forearm occlusion durations. Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).

Conclusion: Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

Show MeSH
Related in: MedlinePlus