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Mark Harbinson - One of the best experts on this subject based on the ideXlab platform.

  • impaired Flow Mediated Dilatation response in uncomplicated type 1 diabetes mellitus influence of shear stress and microvascular reactivity
    Clinical Science, 2011
    Co-Authors: Christopher J Lockhart, Christina E Agnew, Aaron Mccann, Paul Hamilton, Cathy E Quinn, Damien O Mccall, Richard Plumb, Vivienne Mcclenaghan, Canice R Mcgivern, Mark Harbinson
    Abstract:

    Impaired FMD (Flow-Mediated Dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood Flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler Flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P =0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P <0.001). Endothelium-independent Dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P <0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P =0.001). Wavelet interrogation of postischaemic Flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasoDilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability. Abbreviations: ACE, angiotensin-converting enzyme; BMI, body mass index; CI, confidence interval; CV, coefficient of variation; DM, diabetes mellitus; DSS, diastolic shear stress; DWT, discrete wavelet transform; ED, endothelial dysfunction; FMD, Flow-Mediated Dilatation; GTN, glyceryl trinitrate; HbA1C, glycated haemoglobin; PSV, peak systolic velocity; RI, resistive index; STFT, short-time Fourier transform

  • Impaired Flow Mediated Dilatation response in Uncomplicated Type 1 Diabetes Mellitus: influence of shear stress and microvascular reactivity
    Clinical Science, 2011
    Co-Authors: Christopher J Lockhart, Christina E Agnew, Aaron Mccann, Cathy E Quinn, Damien O Mccall, Vivienne Mcclenaghan, Canice R Mcgivern, Paul K Hamilton, Rick D Plumb, Mark Harbinson
    Abstract:

    Objective Impaired Flow-Mediated Dilatation (FMD) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as diabetes mellitus (DM). Endothelium-dependent FMD is a homeostatic response to short-term increases in local shear stress. Microvascular dysfunction in diabetes mellitus influences blood Flow velocity patterns. We explored the determinants of the FMD response in relation to evoked diastolic shear stress (DSS) and forearm microcirculation haemodynamics by quantifying changes in Doppler Flow velocity waveforms between groups. Methods and Results 40 patients with uncomplicated type 1 diabetes and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Post ischaemic Doppler velocity spectral envelopes were recorded, and a wavelet-based time-frequency spectral analysis method employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 vs. 3.94, p=0.23). FMD (%) was significantly impaired in patients with type 1 diabetes (3.95 vs. 7.75, p

Daniel J Green - One of the best experts on this subject based on the ideXlab platform.

  • impact of sympathetic nervous system activity on post exercise Flow Mediated Dilatation in humans
    The Journal of Physiology, 2015
    Co-Authors: Ceri L Atkinson, Dick H J Thijssen, Daniel J Green, Nia C S Lewis, Howard H Carter, Philip N Ainslie
    Abstract:

    Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in Flow-Mediated Dilatation (FMD). Ten healthy male subjects (28 ± 5 years) undertook two 30 min sessions of cycle exercise at 75% HR(max). Prior to exercise, individuals ingested either a placebo or an α1-adrenoreceptor blocker (prazosin; 0.05 mg kg(-1)). Central haemodynamics, brachial artery shear rate (SR) and blood Flow profiles were assessed throughout each exercise bout and in response to brachial artery FMD, measured prior to, immediately after and 60 min after exercise. Cycle exercise increased both mean and antegrade SR (P < 0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre-exercise FMD was similar on both occasions, and was significantly reduced (27%) immediately following exercise in the placebo condition (t-test, P = 0.03). In contrast, FMD increased (37%) immediately following exercise in the prazosin condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD remained different between conditions after correction for baseline diameters preceding cuff deflation and also post-deflation SR. No differences in FMD or other variables were evident 60 min following recovery. Our results indicate that sympathetic vasoconstriction competes with endothelium-dependent dilator activity to determine post-exercise arterial function. These findings have implications for understanding the chronic impacts of interventions, such as exercise training, which affect both sympathetic activity and arterial shear stress.

  • impact of age sex and exercise on brachial artery Flow Mediated Dilatation
    American Journal of Physiology-heart and Circulatory Physiology, 2009
    Co-Authors: Mark A Black, Timothy N Cable, Dick H J Thijssen, Daniel J Green
    Abstract:

    Flow-Mediated Dilatation (%FMD), an index of nitric oxide (NO)-Mediated vasodilator function, is regarded as a surrogate marker of cardiovascular disease. Aging is associated with endothelial dysfunction, but underlying sex-related differences may exist and the effects of fitness and exercise on endothelial dysfunction in men (M) and women (W) are poorly understood. We compared %FMD of the brachial artery in 18 young [Y, 26 +/- 1 yr; 9 M and 9 W], 12 older fit (OF, 57 +/- 2 yr; 6 M and 6 W), and 16 older sedentary (OS, 59 +/- 2 yr; 8 M and 8 W) subjects. Glyceryl trinitrate (GTN) administration was used to assess endothelium-independent vasoDilatation, and the FMD-to-GTN ratio was calculated to characterize NO dilator function in the context of smooth muscle cell sensitivity. Brachial %FMD in Y (7.1 +/- 0.8%) was significantly higher compared with OS (4.8 +/- 0.7%, P < 0.05), but not OF (6.4 +/- 0.7%). Differences between Y and OS subjects were due primarily to lower FMD in the OS women (4.3 +/- 0.6%). OS women exhibited significantly lower FMD-to-GTN ratios compared with Y (P < 0.05) and OF women (P < 0.05), whereas these differences were not apparent in men. Exercise training improved brachial artery NO dilator function (FMD-to-GTN ratio) after 24 wk (P < 0.05) in OS women, but not men. These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents the age-related decline in the brachial artery vasodilator function evident in women. In OS men, who had relatively preserved NO dilator function, no training adaptations were observed. This study has potential implications for the prevention of conduit artery endothelial dysfunction in men and women.

  • Flow Mediated Dilatation in the superficial femoral artery is nitric oxide Mediated in humans
    The Journal of Physiology, 2008
    Co-Authors: Miriam Kooijman, Dick H J Thijssen, Daniel J Green, P C E De Groot, Michiel W P Bleeker, H J M Van Kuppevelt, Gerard A Rongen, Paul Smits, M T E Hopman
    Abstract:

    Flow-Mediated Dilatation (FMD) of the brachial and radial arteries is an important research tool for assessment of endothelial function in vivo, and is nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important territory for studies in exercise physiology. However, the role of endothelial NO in the FMD response of lower limb arteries has never been investigated. The purpose of this study was to examine the contribution of NO to FMD in the superficial femoral artery in healthy subjects. Since physical inactivity may affect endothelial function, and therefore NO availability, spinal cord-injured (SCI) individuals were included as a model of extreme deconditioning. In eight healthy men (34 +/- 13 years) and six SCI individuals (37 +/- 10 years), the 5 min FMD response in the superficial femoral artery was assessed by echo-Doppler, both during infusion of saline and during infusion of the NO synthase blocker N(G)-monomethyl-L-arginine (L-NMMA). In a subset of the controls (n = 6), the 10 min FMD response was also examined using the same procedure. The 5 min FMD response in controls (4.2 +/- 0.3%) was significantly diminished during L-NMMA infusion (1.0 +/- 0.2%, P < 0.001). In SCI, L-NMMA also significantly decreased the FMD response (from 8.2 +/- 0.4% during saline to 2.4 +/- 0.5% during L-NMMA infusion). The hyperaemic Flow response during the first 45 s after cuff deflation was lower in both groups during infusion of L-NMMA, but the effect of L-NMMA on FMD persisted in both groups after correction for the shear stress stimulus. The 10 min FMD was not affected by L-NMMA (saline: 5.4 +/- 1.6%, L-NMMA: 5.6 +/- 1.5%). Superficial femoral artery FMD in response to distal arterial occlusion for a period of 5 min is predominantly Mediated by NO in healthy men and in the extremely deconditioned legs of SCI individuals.

  • importance of measuring the time course of Flow Mediated Dilatation in humans
    Hypertension, 2008
    Co-Authors: Mark A Black, Timothy N Cable, Dick H J Thijssen, Daniel J Green
    Abstract:

    Flow-Mediated Dilatation (FMD) is widely used to describe conduit artery endothelial function. The traditional approaches to FMD calculation assess diameter change at arbitrary time points after occluding cuff deflation. The aim of this study was to examine the time course of brachial artery FMD after a 5-minute period of forearm ischemia in 12 young, 12 fitness matched older and 12 older untrained subjects. Edge-detection and wall tracking of high resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate brachial artery diameter, blood Flow, and shear rate continuously across the cardiac cycle after forearm ischemia. FMD was significantly higher in young healthy subjects (7.8+/-3.2%) compared with sedentary older subjects (5.2+/-2.8%, P 42%) of true peak diameters fell outside the time frames typically used to assess FMD in the literature. When calculated according to the commonly used approach, ie, 60 s after cuff deflation, FMD was significantly lower compared with true peak FMD in all groups (P<0.001), and no differences were evident between the groups. The time course of FMD differs significantly between young and older subjects. Studies assuming that peak dilation occurs at an arbitrary time point, or within limited time windows, may draw misleading conclusions regarding differences between groups. More sophisticated approaches to measurement of FMD are required if it is to be considered a valid biomarker of vascular disease.

Christopher J Lockhart - One of the best experts on this subject based on the ideXlab platform.

  • impaired Flow Mediated Dilatation response in uncomplicated type 1 diabetes mellitus influence of shear stress and microvascular reactivity
    Clinical Science, 2011
    Co-Authors: Christopher J Lockhart, Christina E Agnew, Aaron Mccann, Paul Hamilton, Cathy E Quinn, Damien O Mccall, Richard Plumb, Vivienne Mcclenaghan, Canice R Mcgivern, Mark Harbinson
    Abstract:

    Impaired FMD (Flow-Mediated Dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood Flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler Flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P =0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P <0.001). Endothelium-independent Dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P <0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P =0.001). Wavelet interrogation of postischaemic Flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasoDilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability. Abbreviations: ACE, angiotensin-converting enzyme; BMI, body mass index; CI, confidence interval; CV, coefficient of variation; DM, diabetes mellitus; DSS, diastolic shear stress; DWT, discrete wavelet transform; ED, endothelial dysfunction; FMD, Flow-Mediated Dilatation; GTN, glyceryl trinitrate; HbA1C, glycated haemoglobin; PSV, peak systolic velocity; RI, resistive index; STFT, short-time Fourier transform

  • Impaired Flow Mediated Dilatation response in Uncomplicated Type 1 Diabetes Mellitus: influence of shear stress and microvascular reactivity
    Clinical Science, 2011
    Co-Authors: Christopher J Lockhart, Christina E Agnew, Aaron Mccann, Cathy E Quinn, Damien O Mccall, Vivienne Mcclenaghan, Canice R Mcgivern, Paul K Hamilton, Rick D Plumb, Mark Harbinson
    Abstract:

    Objective Impaired Flow-Mediated Dilatation (FMD) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as diabetes mellitus (DM). Endothelium-dependent FMD is a homeostatic response to short-term increases in local shear stress. Microvascular dysfunction in diabetes mellitus influences blood Flow velocity patterns. We explored the determinants of the FMD response in relation to evoked diastolic shear stress (DSS) and forearm microcirculation haemodynamics by quantifying changes in Doppler Flow velocity waveforms between groups. Methods and Results 40 patients with uncomplicated type 1 diabetes and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Post ischaemic Doppler velocity spectral envelopes were recorded, and a wavelet-based time-frequency spectral analysis method employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 vs. 3.94, p=0.23). FMD (%) was significantly impaired in patients with type 1 diabetes (3.95 vs. 7.75, p

Olli T Raitakari - One of the best experts on this subject based on the ideXlab platform.

  • adiponectin is related with carotid artery intima media thickness and brachial Flow Mediated Dilatation in young adults the cardiovascular risk in young finns study
    Annals of Medicine, 2010
    Co-Authors: Liisa A Saarikoski, Markus Juonala, Mika Kahonen, Jukka Marniemi, Jorma Viikari, Risto Huupponen, Olli T Raitakari
    Abstract:

    AbstractAims. Adiponectin may be involved in the pathogenesis of atherosclerosis. We investigated the relation of adiponectin on early functional and structural markers of subclinical atherosclerosis in a large population-based cohort of young men and women.Methods and results. We measured serum adiponectin using radioimmunoassay in 2,147 young adults (ages 24–39 years) participating in the Cardiovascular Risk in Young Finns Study. The subjects had ultrasound data on carotid intima-media thickness (IMT), carotid artery elasticity (n = 2,139) and brachial Flow-Mediated Dilatation (FMD) (n = 1,996). In univariate analysis, adiponectin was inversely associated with IMT (r = −0.16, P < 0.0001) and directly with FMD (r = 0.12, P < 0.0001) and carotid elasticity (r = 0.20, P < 0.0001). The associations for IMT and FMD remained significant in multivariable models adjusted for age, sex, obesity indices, serum lipids, blood pressure, leptin, glucose, and C-reactive protein: IMT (β = −0.018 ± 0.005, P = 0.0002) and...

  • determinants of short term variation in arterial Flow Mediated Dilatation in healthy young men
    Clinical Science, 2006
    Co-Authors: Mikko J Jarvisalo, Terho Lehtimaki, Laura Jartti, Jukka Marniemi, Tapani Ronnemaa, Jorma Viikari, Olli T Raitakari
    Abstract:

    Brachial artery FMD (Flow-Mediated Dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

  • deletion polymorphism in the α2b adrenergic receptor gene is associated with Flow Mediated Dilatation of the brachial artery
    Clinical Science, 2002
    Co-Authors: Paula Heinonen, Mikko J Jarvisalo, Laura Jartti, Tapani Ronnemaa, Olli T Raitakari, Ullamari Pesonen, Jaakko Kaprio, Mika Scheinin
    Abstract:

    A deletion variant of the alpha(2B)-adrenergic receptor (alpha(2B)-AR) has been associated with an increased risk of acute cardiac events in middle-aged men. Our aim was to determine the possible associations between the alpha(2B)-AR gene deletion variant and indicators of subclinical atherosclerosis in the brachial and carotid arteries. A total of 148 middle-aged men participating in an epidemiological twin study on risk factors for subclinical coronary heart disease were genotyped using PCR. Flow-Mediated Dilatation (FMD) of the brachial artery, carotid artery compliance and carotid intima-media thickness were measured using high-resolution ultrasound. FMD was 6.2+/-5.0% in subjects with the I/I (insertion/insertion) genotype, 5.5+/-4.1% in the I/D (insertion/deletion) group and 4.1+/-3.8% in the D/D (deletion/deletion) group ( P =0.03 for trend). In multivariate regression analysis controlling for age, presence of hypertension, smoking, use of angiotensin-converting enzyme inhibitors and plasma levels of low-density lipoprotein cholesterol and lipoprotein (a), the association between the alpha(2B)-AR genotype and FMD remained significant ( P =0.04 for trend). The alpha(2B)-AR genotype was not associated with intima-media thickness or carotid artery compliance. These findings indicate that subjects homozygous for the deletion allele of alpha(2B)-AR appear to have an increased risk of impaired endothelial function, which may provide an explanation for the previously observed increased risk of myocardial infarction in male subjects with this genotype. It is not known whether the association of the alpha(2B)-AR polymorphism with endothelial function is direct, or is Mediated via altered sympathetic activation.

Cihan Örem - One of the best experts on this subject based on the ideXlab platform.