Flow-mediated dilation analysis coupled with nitric oxide transport to enhance the assessment of endothelial function

Author(s):  
Tianxiang Ma ◽  
Xiao Liu ◽  
Quan Ren ◽  
Zhexi Zhang ◽  
Xiaoning Sun ◽  
...  

Flow-mediated dilation (FMD), mainly mediated by nitric oxide (NO), aims to assess the shear-induced endothelial function, which is widely quantified by the relative change in arterial diameter after dilation (FMD%). However, FMD% is affected by individual differences in blood pressure, blood flow and arterial diameter. To reduce these differences and enhance the assessment of FMD to endothelial function, we continuously measured not only the brachial artery diameter and blood flow with ultrasound but also blood pressure with non-invasive monitor during standard FMD test. We further constructed an analytical model of FMD coupled with NO transport, blood flow, and arterial deformation. Combining the time-averaged and peak values of arterial diameter, blood flow and pressure, and the modeling, we assumed the artery was completely healthy and calculated an ideally expected FMD% (eFMD%). Then, we expressed the fractional flow-mediated dilation (FFMD%) for the ratio of measured FMD% (mFMD%) to eFMD%. Furthermore, using the continuous waveforms of arterial diameter, blood flow and pressure, the endothelial characteristic parameter (ϵ) was calculated, which describes the function of the endothelium to produce NO and ranges from 1 to 0 representing the endothelial function from healthiness to complete loss. We found that the mFMD% and eFMD% between the young age (n=5, 21.2±1.8yr) and middle age group (n=5, 34.0±2.1yr) have no significant difference (P=0.222, P=0.385). In contrast, the FFMD% (P=0.008) and ϵ (P=0.007) both show significant differences. Therefore, the fractional flow-mediated dilation (FFMD%) and the endothelial characteristic parameter (ϵ) may have the potential for specifically diagnosing the endothelial function.

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Teresa K. Chen ◽  
Ronit Katz ◽  
Michelle M. Estrella ◽  
Wendy S. Post ◽  
Holly Kramer ◽  
...  

Background APOL1 high‐risk genotypes are associated with increased risk for hypertension‐attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross‐sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow‐mediated dilation, n=777). Using linear mixed‐effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high‐risk) Black participants in MESA (Multi‐Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000–2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow‐mediated dilation in participants with APOL1 high‐ versus low‐risk genotypes ( P >0.05 for all). Over a mean follow‐up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between‐group differences of −0.20, −0.14, and −0.25, respectively; P >0.05 for all). Conclusions Among Black participants in MESA, APOL1 high‐risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.


2010 ◽  
Vol 298 (1) ◽  
pp. H119-H126 ◽  
Author(s):  
Kyra Pyke ◽  
Daniel J. Green ◽  
Cara Weisbrod ◽  
Matthew Best ◽  
Lawrence Dembo ◽  
...  

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.


1997 ◽  
Vol 2 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Akimi Uehata ◽  
Eric H Lieberman ◽  
Marie D Gerhard ◽  
Todd J Anderson ◽  
Peter Ganz ◽  
...  

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.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 984-984
Author(s):  
Sharon E. Cox ◽  
Julie Makani ◽  
Elizabeth Ellins ◽  
Gurishaeli Walter ◽  
Selemani Mtunguja ◽  
...  

Abstract Introduction Endothelial function is impaired in adults with sickle cell anaemia (SCA), but limited data exists in children. Endothelial damage occurs from chronic inflammation, oxidant damage, immune cell activation and ischemia-reperfusion injury. In addition, availability of nitric oxide (NO) as the major vasodilator may be reduced as a result of scavenging by plasma haemoglobin and reduced arginine substrate for endothelial nitric oxide synthase. Methods Tanzanian children (N=119) with SCA (HbSS) aged 8-11.9 years enrolled in the Vascular Function Intervention Trial (ISRCTN74331412/NCT01718054) underwent baseline assessment of endothelium-dependent and -independent vasodilatation. All children were determined clinically well at assessment, hydroxyurea naive, on no long-term medication and not receiving chronic blood transfusions. Blood pressure and vasomotion were assessed after 10 minutes recumbent rest in a temperature controlled room between 08-13:00 hrs. An identical protocol as published in children (Donald & Charakida et al. Eur Heart J; 2010: 31; 1502-10) was used. In brief, brachial arterial endothelium dependent dilatation was assessed by 1 of 3 trained technicians using ultrasound imaging (Ultrasonix SonixTouch with a 12Mz probe & stereotactic holder) to assess flow-mediated dilatation (FMD) in response to reactive hyperaemia induced after release of transient blood pressure cuff occlusion (5 min, 200 mmHg, Hokanson, USA) using an automated air regulator (Logan Research, UK). Automated B-mode image edge detection was used to measure maximum change in arterial diameter (Brachial Tools) expressed as a percentage of resting baseline diameter (FMDmax). Endothelium-independent responses to 2.5µg sub-lingual glyceryl-trinitrate (GTN) were also assessed. All recordings were over-read by an experienced researcher in the UK. Venepuncture for full blood count, clinical chemistry and amino acids was conducted after FMD assessment. Results Patient characteristics are described in Table 1. Mean brachial artery diameter at baseline was 2.61mm (95% CI 2.55 – 2.67mm). Mean FMDmax was 7.70% (95% CI 7.09 – 8.32%). Endothelium-independent vasodilation (GTNmax) was 4.15% (95% CI 3.83 – 4.47%). The FMDmax response was on greater than the GTNmax response (Figure 1). No effect of room or skin temperature on FMDmax or GTNmax was observed. There was a strong inverse association between baseline artery diameter and FMDmax (-3.46, P<0.001) (Figure 2). The time to peak brachial artery diameter in response to hyperaemia was positively skewed (median 55s (IQR: 43-79s)) and was not associated with FMDmax. The only patient characteristic associated with FMDmax was age with a non-significant inverse correlation (-0.52, P=0.06) but was reduced when adjusting for baseline diameter. Baseline heart rate was positively associated with FMDmax and GTNmax (P=0.01 & 0.025). Discussion We have characterised peripheral vascular function in a large cohort of children with SCA. Mean FMDmax was slightly lower than that observed in predominantly Caucasian non-SCA British children of similar age (8.1% [SD3.4]) (Donald & Charakida et al. Eur Heart J 2010: 31; 1502-10), but higher than reported in 21 older French children with SCA (5.6 +/- 0.2) (Montalembert et al. Haematol 2007: 92; 1709-10) which might reflect deterioration of endothelial function with age. There was no apparent association between FMDmax and hemolytic markers or with nutritional status at baseline. Recruitment and assessment of appropriate local non-SCA controls for comparison is planned. Amino acid analyses are ongoing. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 25 (17) ◽  
pp. 1875-1883 ◽  
Author(s):  
Manuel Stern ◽  
Melanie Broja ◽  
Roberto Sansone ◽  
Michael Gröne ◽  
Simon S Skene ◽  
...  

Aims Previous studies have shown that ultraviolet light can lead to the release of nitric oxide from the skin and decrease blood pressure. In contrast to visible light the local application of ultraviolet light bears a cancerogenic risk. Here, we investigated whether whole body exposure to visible blue light can also decrease blood pressure and increase endothelial function in healthy subjects. Methods In a randomised crossover study, 14 healthy male subjects were exposed on 2 days to monochromatic blue light or blue light with a filter foil (control light) over 30 minutes. We measured blood pressure (primary endpoint), heart rate, forearm vascular resistance, forearm blood flow, endothelial function (flow-mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite and nitroso compounds (secondary endpoints) during and up to 2 hours after exposure. Results Blue light exposure significantly decreased systolic blood pressure and increased heart rate as compared to control. In parallel, blue light significantly increased forearm blood flow, flow-mediated dilation, circulating nitric oxide species and nitroso compounds while it decreased forearm vascular resistance and pulse wave velocity. Conclusion Whole body irradiation with visible blue light at real world doses improves blood pressure, endothelial function and arterial stiffness by nitric oxide released from photolabile intracutanous nitric oxide metabolites into circulating blood.


Author(s):  
Gustavo Vieira de Oliveira ◽  
Elisaldo Mendes Cordeiro ◽  
Mônica Volino-Souza ◽  
Cristina Rezende ◽  
Carlos Adam Conte-Junior ◽  
...  

The current pool of data investigating the effects of a single resistance exercise session on endothelial function is divergent and inconclusive. Therefore, the purpose of the present study was to evaluate the effect of a single resistance exercise session on flow-mediated dilation (FMD) in trained individuals. Eleven healthy, young, recreationally resistance-trained individuals participated in the study. After determining the resistance exercise workload, the participants performed three sets of 10–12 repetition of leg press and leg extension exercises. By using ultrasound equipment, brachial artery FMD was assessed before (PRE) and 30 min after (POST) the resistance exercise protocol or resting (control) to evaluate endothelial function. A significant reduction in FMD response (PRE: 5.73% ± 1.21% vs. POST: 4.03% ± 1.94%, p < 0.01) after resistance exercise was observed, accompanied by a large effect size (d = 1.05). No significant difference was observed in FMD in the control condition (PRE: 5.82% ± 1.19% vs. POST: 5.66% ± 1.24%, p = 0.704). Additionally, no significant difference in baseline brachial artery diameter between resistance exercise (PRE: 3.30 ± 0.32 vs. POST: 3.40 ± 0.34 mm, p = 0.494) and resting (PRE: 3.64 ± 0.41 vs. POST: 3.67 ± 0.62 mm, p = 0.825) was observed. Our findings showed that a single resistance exercise session induced a reduction in FMD in resistance-trained individuals.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Nozomu Oda ◽  
Yukihito Higashi ◽  
Masato Kajikawa ◽  
Tatsuya Maruhashi ◽  
Akimichi Iwamoto ◽  
...  

Introduction: Endothelial function is impaired in heavy or binge drinking. Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of dose-dependent alcohol consumption on endothelial function. Therefore, we evaluated the relationship between alcohol consumption and endothelial function in a large general population. Methods and Results: We measured flow-mediated vasodilation (FMD) in 2734 men who provided self-report about habitual alcohol intake. The subjects were divided into five groups by alcohol consumption: none (0 g/week), light (0 g/week< to ≤140 g/week), moderate (140 g/week< to ≤280 g/week), heavy (280 g/week< to ≤420 g/week), and excessive (420 g/week<). Age, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, gamma glutamyl transpeptidase, uric acid, plasma glucose, hemoglobin A1c, and current smoking were significantly correlated with alcohol consumption. FMD showed a gradual decrease according to increased alcohol consumption (none, 6.6±3.4%; light, 6.2±3.0%; moderate, 6.0±3.0%; heavy, 5.5±2.9%; excessive, 5.3±3.0%; P<0.01). There was a significant difference in FMD between the non-drinker group and the light drinker group (P=0.018). After adjusted risk factors, we showed the significantly smaller FMD in the 4 drinker groups than in the non-drinker group: light drinker group (OR, 1.38; 95% CI, 1.10 to 1.75), moderate drinker group (OR, 1.36; 95% CI, 1.01 to 1.82), heavy drinker group (OR, 2.05; 95% CI, 1.46 to 2.87), excessive drinker group (OR, 2.04; 95% CI, 1.43 to 2.89). Conclusions: These findings suggest that even light alcohol consumption impair the endothelial function. Alcohol drinking may be harmful for vascular function.


2005 ◽  
Vol 99 (4) ◽  
pp. 1621-1621 ◽  
Author(s):  
Clare E. Austin

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).


2007 ◽  
Vol 112 (7) ◽  
pp. 403-409 ◽  
Author(s):  
Cheri L. Mcgowan ◽  
Andrew S. Levy ◽  
Neil Mccartney ◽  
Maureen J. Macdonald

Isometric HG (handgrip) training lowers resting arterial BP (blood pressure), yet the mechanisms are elusive. In the present study, we investigated improved systemic endothelial function as a mechanism of arterial BP modification following isometric HG training in normotensive individuals. This study employed a within-subject repeated measures design primarily to assess improvements in BA FMD (brachial artery flow-mediated dilation; an index of endothelium-dependent vasodilation), with the non-exercising limb acting as an internal control. Eleven subjects performed four 2-min unilateral isometric HG contractions at 30% of maximal effort, three times per week for 8 weeks. Pre-, mid- and post-training resting ABP and BA FMD (exercised arm and non-exercised arm) were measured via automated brachial oscillometry and ultrasound respectively. BA FMD (normalized to the peak shear rate experienced in response to the reactive hyperaemic stimulus) remained unchanged [exercised arm, 0.029±0.003 to 0.026±0.003 to 0.029±0.004%/s−1 (pre- to mid- to post-training respectively); non-exercised arm, 0.023±0.003 to 0.023±0.003 to 0.024±0.003%/s−1 (pre- to mid- to post-training respectively); P=0.22]. In conclusion, improved systemic endothelial function is unlikely to be responsible for lowering arterial BP in this population.


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