Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a ...

Georgia Regents University

Overactivity of the epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In an open-labeled, nonplacebo-controlled clinical trial (Clinicaltrials.gov: NCT-01308983), the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). The mean body mass index of participants was 28.45±1.30 kg/m(2) . Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.

Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.

Preclinical data have demonstrated that heart rate (HR) can directly impact vascular endothelial function, in part, through a shear-stress mechanism. This study sought to explore, in humans, the associations between resting heart rate and both shear and endothelial function assessed by flow-mediated dilation (FMD). The brachial artery FMD test was performed in 31 apparently healthy volunteers. Basal (B) and hyperaemic (H) shear were quantified in the following two ways using data from the FMD test: the traditional cumulative shear area under the curve up to peak dilation (Shearcum) method; and our novel method of shear summation (Shearsum), which accounts for HR by summing each individual cardiac cycle shear up to peak dilation. Data were grouped by tertiles based on resting HR as follows: low (LHR = 43-56 beats min(-1); n = 10); middle (MHR = 58-68 beats min(-1); n = 11); and high (HHR = 69-77 beats min(-1); n = 10). Within the LHR group, both B-Shearcum and H-Shearcum were significantly higher (P < 0.001) than B-Shearsum and H-Shearsum, respectively, whereas in the HHR group B-Shearcum and H-Shearcum were significantly lower (P < 0.001) than B-Shearsum and H-Shearsum, respectively. The FMD in the LHR group (8.8 ± 0.8%) was significantly greater than that in both the MHR group (5.5 ± 0.8%; P = 0.009) and the HHR group (5.9 ± 0.8%; P = 0.024). These findings demonstrate the existence of a relationship between heart rate and both shear and endothelial function in humans. Moreover, these findings have implications for considering heart rate as an important physiological variable when quantifying shear and performing the FMD test.

Association beween resting heart rate, shear and flow-mediated dilation in healthy adults.

What is the central question of this study? Do patients with cystic fibrosis have reduced skeletal muscle oxidative capacity, measured with near-infrared spectroscopy, compared with demographically matched control subjects? What is the main finding and is its importance? Patients with cystic fibrosis have impairments in skeletal muscle oxidative capacity. This reduced skeletal muscle oxidative capacity not only appears to be accelerated by age, but it may also contribute to exercise intolerance in patients with cystic fibrosis. Exercise intolerance predicts mortality in patients with cystic fibrosis (CF); however, the mechanisms have yet to be elucidated fully. Using near-infrared spectroscopy, in this study we compared skeletal muscle oxidative capacity in patients with CF versus healthy control subjects. Thirteen patients and 16 demographically matched control subjects participated in this study. Near-infrared spectroscopy was used to measure the recovery rate of oxygen consumption ( mus V̇O2max) of the vastus lateralis muscle after 15 s of electrical stimulation (4 Hz) and subsequent repeated transient arterial occlusions. The mus V̇O2max was reduced in patients with CF (1.82 ± 0.4 min(-1) ) compared with control subjects (2.13 ± 0.5 min(-1) , P = 0.04). A significant inverse relationship between age and mus V̇O2max was observed in patients with CF (r = -0.676, P = 0.011) but not in control subjects (r = -0.291, P = 0.274). Patients with CF exhibit a reduction in skeletal muscle oxidative capacity compared with control subjects. It appears that the reduced skeletal muscle oxidative capacity is accelerated by age and could probably contribute to exercise intolerance in patients with CF.

Skeletal muscle oxidative capacity in patients with cystic fibrosis.

Exercise capacity, an objective measure of exercise intolerance, is known to predict quality of life and mortality in cystic fibrosis (CF). The mechanisms for exercise intolerance in patients with cystic fibrosis (CF), however, have yet to be fully elucidated. Accordingly, this study sought to investigate oxygen uptake kinetics and the impact of fat-free mass (FFM) on exercise capacity in young patients with CF. 16 young patients with CF (age 13 ± 4 years; 10 female) and 15 matched controls (age 14 ± 3 years; nine female) participated. Pulmonary function and a maximal exercise test on a cycle ergometer using the Godfrey protocol were performed. Exercise capacity (VO2 peak), VO2 response time (VO2 RT), and functional VO2 gain (ΔVO2 /ΔWR) were all determined. Lung function was the only demographic parameter significantly lower (P < 0.05) in CF compared to controls. Exercise capacity was lower in CF (P < 0.014) only when VO2 peak was normalized for FFM (43.5 ± 7.7 vs. 50.6 ± 7.4 ml/kg-FFM/min) or expressed as % predicted (70.1 ± 14.3 vs. 85.4 ± 16.0%). The VO2 RT was slower (36.1 ± 15.1 vs. 25.0 ± 12.4 sec; P = 0.03) and the ΔVO2 /ΔWR slope was lower (8.4 ± 3 ml/min/watt vs. 10.1 ± 1.4 ml/min/watt; P = 0.02) in patients compared to controls, respectively. In conclusion, a delayed VO2 response time coupled with the lower functional VO2 gain (ΔVO2 /ΔWR) suggest that young patients with CF have impairment in oxygen transport and oxygen utilization by the muscles. These data in addition to differences in VO2 peak normalized for FFM provide some insight that muscle mass and muscle metabolism contribute to exercise intolerance in CF.

Oxygen uptake kinetics and exercise capacity in children with cystic fibrosis.

Elevated cardiovascular disease risk is observed in patients with COPD. Non-invasive assessments of endothelial dysfunction and arterial stiffness have recently emerged to provide mechanistic insight into cardiovascular disease risk in COPD; however, the reproducibility of endothelial function and arterial stiffness has yet to be investigated in this patient population.

Assessments of endothelial function and arterial stiffness are reproducible in patients with COPD.

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether or not microvascular function is affected in this population has yet to be elucidated. Using laser Doppler imaging, we evaluated endothelial microvascular function through post-occlusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (Ach). Compared with controls (C), patients with CF showed a significantly lower PORH (CF: 518 ± 45 vs. C: 8015 ± 103 %, p=0.039), LTH (CF: 1152 ± 112 vs. C: 1572 ± 166 %, p=0.045), and iontophoresis with Ach (CF: 416 ± 39 vs. C: 617 ± 41 %, p=0.032). In addition, a significantly (p=0.043) lower PORH/LTH ratio was identified in patients with CF (55.3 ± 2.9 %) compared to controls (68.8 ± 1.8 %). Significant positive correlations between LTH and FEV1 (% predicted; r=0.441; p=0.013) and between PORH/LTH ratio and exercise capacity (r=0.350; p=0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with controls. In addition, our data demonstrate the existence of a complex relationship between microvascular endothelial function and classical markers of disease severity (i.e. pulmonary function and exercise capacity) in CF.

Nichole Seigler

Division of Clinical and Translational Sciences,
Georgia Prevention Institute,
Division of Clinical and Translational Sciences, Georgia Prevention Institute

Georgia Regents University

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Nichole Seigler

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Division of Clinical and Translational Sciences,Georgia Prevention Institute,Division of Clinical and Translational Sciences, Georgia Prevention Institute

Georgia Regents University

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Division of Clinical and Translational Sciences,
Georgia Prevention Institute,
Division of Clinical and Translational Sciences, Georgia Prevention Institute