Limits...
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.

Show MeSH

Related in: MedlinePlus

Time course of forearm oxygen tissue saturation (NIRS) in conjunction with brachial artery blood flow (ultrasound). Values are means. *Volume of ischemia (StO2AUC) significantly different from all other trials; #Volume of ischemia (StO2AUC) significantly different from 3-min, 4-min, and 5-min; &Peak ischemia (StO2peak) significantly different from all other trials; ^ Peak ischemia (StO2peak) significantly different from 1-min, 2-min, and 3-min. All p < 0.0001. Ultrasound data were not collected during the occlusion periods.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2542351&req=5

Figure 3: Time course of forearm oxygen tissue saturation (NIRS) in conjunction with brachial artery blood flow (ultrasound). Values are means. *Volume of ischemia (StO2AUC) significantly different from all other trials; #Volume of ischemia (StO2AUC) significantly different from 3-min, 4-min, and 5-min; &Peak ischemia (StO2peak) significantly different from all other trials; ^ Peak ischemia (StO2peak) significantly different from 1-min, 2-min, and 3-min. All p < 0.0001. Ultrasound data were not collected during the occlusion periods.

Mentions: Demographic information of the subjects is summarized in Table 1. No effect of sex was found in any of the main outcome variables (SS60secAUC, peak FMD response, FMD:SSAUC ratio), thus data were pooled across sex. Table 2 displays mean baseline values for brachial artery diameter, blood velocity, shear stress, heart rate and forearm oxygen tissue saturation. No differences in baseline values were found (p > 0.05) for any of the variables. NIRS data on one subject was lost, thus sample size was 19 for all NIRS-related analysis. Figure 3 illustrates the time course of forearm oxygen tissue saturation in conjunction with brachial artery blood flow across the different forearm occlusion conditions. As indicated, the volume of ischemia and peak ischemia increased incrementally with duration of forearm occlusion (F(4,72) = 102.6; p < 0.0001 and F(4,72) = 69.85; p < 0.0001, respectively). Figure 4 illustrates the effects of forearm occlusion duration on the magnitude of reactive hyperemia-induced shear stress (panel A), peak FMD response (panel B), and FMD normalized to shear stress (panel C). As shown, varying forearm occlusion duration effectively elicited five different magnitudes of reactive hyperemia-induced shear stress (F(4,76) = 97.6; p < 0.0001). As a result, differences in peak FMD response were detected among conditions (F(4,76) = 40.5; p < 0.0001); however, these discrepancies were abolished when normalizing FMD to the shear stress (peak FMD:SSAUC ratio) (F(4,76) = 0.43; p = 0.785).


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)

Time course of forearm oxygen tissue saturation (NIRS) in conjunction with brachial artery blood flow (ultrasound). Values are means. *Volume of ischemia (StO2AUC) significantly different from all other trials; #Volume of ischemia (StO2AUC) significantly different from 3-min, 4-min, and 5-min; &Peak ischemia (StO2peak) significantly different from all other trials; ^ Peak ischemia (StO2peak) significantly different from 1-min, 2-min, and 3-min. All p < 0.0001. Ultrasound data were not collected during the occlusion periods.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Time course of forearm oxygen tissue saturation (NIRS) in conjunction with brachial artery blood flow (ultrasound). Values are means. *Volume of ischemia (StO2AUC) significantly different from all other trials; #Volume of ischemia (StO2AUC) significantly different from 3-min, 4-min, and 5-min; &Peak ischemia (StO2peak) significantly different from all other trials; ^ Peak ischemia (StO2peak) significantly different from 1-min, 2-min, and 3-min. All p < 0.0001. Ultrasound data were not collected during the occlusion periods.
Mentions: Demographic information of the subjects is summarized in Table 1. No effect of sex was found in any of the main outcome variables (SS60secAUC, peak FMD response, FMD:SSAUC ratio), thus data were pooled across sex. Table 2 displays mean baseline values for brachial artery diameter, blood velocity, shear stress, heart rate and forearm oxygen tissue saturation. No differences in baseline values were found (p > 0.05) for any of the variables. NIRS data on one subject was lost, thus sample size was 19 for all NIRS-related analysis. Figure 3 illustrates the time course of forearm oxygen tissue saturation in conjunction with brachial artery blood flow across the different forearm occlusion conditions. As indicated, the volume of ischemia and peak ischemia increased incrementally with duration of forearm occlusion (F(4,72) = 102.6; p < 0.0001 and F(4,72) = 69.85; p < 0.0001, respectively). Figure 4 illustrates the effects of forearm occlusion duration on the magnitude of reactive hyperemia-induced shear stress (panel A), peak FMD response (panel B), and FMD normalized to shear stress (panel C). As shown, varying forearm occlusion duration effectively elicited five different magnitudes of reactive hyperemia-induced shear stress (F(4,76) = 97.6; p < 0.0001). As a result, differences in peak FMD response were detected among conditions (F(4,76) = 40.5; p < 0.0001); however, these discrepancies were abolished when normalizing FMD to the shear stress (peak FMD:SSAUC ratio) (F(4,76) = 0.43; p = 0.785).

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