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To investigate the effect of a heart rate (HR) lowering agent (Ivabradine) on features of atherosclerotic plaque vulnerability with magnetic resonance imaging (MRI), ultrasound imaging, and histology.Atherosclerosis was induced in the abdominal aorta of 19 rabbits. Nine rabbits were treated with Ivabradine (17 mg/kg/day) during the entire study period. At week 14, imaging was performed. Plaque size was quantified on contrast-enhanced T1-weighted MR images. Microvascular flow, density, and permeability was studied with dynamic contrast-enhanced MRI. Plaque biomechanics was studied by measuring the aortic distension with ultrasound. After, animals were sacrificed and histology was performed. HR was reduced by 16% (p = 0.026) in Ivabradine-treated animals. No differences in absolute and relative vessel wall beat-to-beat distension were found, but due to the reduction in HR, the frequency of the biomechanical load on the plaque was reduced. Plaque size (MR and histology) was similar between groups. Although microvessel density (histology) was similar between groups, AUC and Ktrans, indicative for plaque microvasculature flow, density, and permeability, were decreased by 24% (p = 0.029) and 32% (p = 0.037), respectively. Macrophage content (relative RAM11 positive area) was reduced by 44% (p

Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMDv and mFMDv, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD), the peak to baseline diameter ratio (Dpeak/Dbase), and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shearAUC) or with area integrated to peak hyperemia (FMD/shearAUC_peak)]. Inter-session and intra-session reproducibilities for pFMDv, mFMDv and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range). Both pFMDv and mFMDv showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001) than the other indices (% given are relative reductions): %FMD (~11%, p≥0.074); Dpeak/Dbase (~11%, p≥0.074); FMD/shearAUC_peak (~20%, p≥0.016) and FMD/shearAUC (~38%, p≤0.038). Further analysis indicated that wall shear stress normalization under normal (fasting) conditions is already far from ideal (FMDv << 1), which (therefore) does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.

Quantitative targeted ultrasound contrast imaging demands for contrast agents with a small monodisperse size and a high coverage of specific ligands for effective adhesion under physiological shear stress conditions. However, the particles should also be large enough to generate sufficient ultrasound reflection. Standard perfluorocarbon emulsions do not satisfy both requirements (adhesion and echogenicity). Therefore, we decided to develop a membrane emulsification technique to produce echogenic monodisperse perfluorohexane emulsions able to carry specific ligands for adhesion to the artery wall. In this work, we demonstrate that membrane emulsification is an excellent tool to create strictly monodisperse echogenic perfluorohexane emulsions with a preset droplet size. Perfluorohexane is emulsified in water using photolithographic microsieves. An ultrasound experiment demonstrates that the perfluorohexane emulsions clearly enhance echogenicity. The acoustic enhancement varies with droplet size and surface coverage. The emulsions, with a biotinylated fluoro-surfactant, are able to bind avidin coated SiO2particles. This proves that these emulsions show a very promising potential to act as key species in the field of selective targeting, which can provide novel insights into the development and early detection of important vascular diseases, e.g.atherosclerosis. [ABSTRACT FROM AUTHOR]

Background. Structural abnormalities of the common carotid artery (CCA), as assessed by ultrasound techniques, are related to cardiovascular outcome in dialysis patients. An increased intima media thickness (IMT) of the CCA may both represent a reaction to a haemodynamic burden as well as atherosclerosis. With a new ultrasound technique CCA-IMT and IMT-inhomogeneity, a novel parameter of spatial variance of the IMT, were measured and related to traditional and non-traditional risk factors.Methods. In a cross-sectional study, we included 134 dialysis patients, aged 61 ± 13 years (103 on haemodialysis, 31 on peritoneal dialysis) and 41 controls, aged 60 ± 8 years. Age, sex, pulse pressure, diabetes, prevalent cardiovascular disease (CVD) and height were included in the basic multiregression analysis. Ultrasound examination of the CCA was performed. We also measured serum fetuin-A, high-sensitivity C-reactive protein (hsCRP), antibodies to oxidized low density lipoproteins (anti-oxLDL antibodies), calcium, phosphate, albumin and parathyroid hormone.Results. Compared with controls, dialysis patients had a greater CCA-IMT (670 μm vs 590 ± 10 μm; P = 0.002) and a greater CCA-IMT inhomogeneity (11.0 vs 8.1%; P = 0.013). Dialysis patients with CVD had a greater CCA-IMT (734 μm vs 631μm; P = 0.001) and IMT-inhomogeneity (13.2 vs 9.7; P = 0.008) compared with patients without CVD. IMT-inhomogeneity strongly correlated with IMT (R = 0.65, P < 0.0001). In multiregression analysis, serum fetuin-A and anti-oxLDL antibodies correlated with IMT-inhomogeneity but not with IMT. HsCRP neither correlated with IMT-inhomogeneity nor with IMT.Conclusion. The present study shows that CCA-IMT and IMT-inhomogeneity were increased in dialysis patients compared with controls. Although CCA-IMT and IMT-inhomogeneity are related, the different associations between both measurements and non-traditional risk factors show that they are distinct entities. [ABSTRACT FROM AUTHOR]

Background. An increase in aortic stiffness, as reflected by an increase in pulse wave velocity (PWV) or aortic augmentation index (AI) is an important predictor of cardiovascular mortality in dialysis patients. Dysregulation of calcification inhibitors, such as fetuin-A, is involved in vascular pathology in dialysis patients and fetuin-A is inversely related to mortality in dialysis patients. In this study, the relation between serum fetuin-A concentration and parameters of aortic stiffness was investigated in patients with end-stage renal disease.Methods. In a cross-sectional study we included 131 dialysis patients, aged 62±14 years (33 on peritoneal dialysis and 98 on haemodialysis), and 41 controls, aged 60±8 years. Time-averaged pre-dialysis values of serum albumin, Ca, P and intact parathyroid hormone were included in multiregression analysis, as were high-sensitivity C-reactive protein (hsCRP), fetuin-A, age, mean arterial pressure (MAP) and dialysis modality. PWV and AI were measured with the SphygmoCor device.Results. Mean fetuin-A concentration in dialysis patients (0.63±0.16 g/l) did not differ from controls (0.63±0.11 g/l). Median hsCRP levels in dialysis patients were higher compared with controls (4.0 vs 1.9 mg/l; P<0.0001). PWV but not AI was higher in dialysis patients than in controls (9.9 vs 7.9 m/s; P<0.0001). In univariate analysis in dialysis patients, fetuin-A levels were inversely related to both PWV (r = − 0.25, P = 0.007) and AI (r = − 0.26, P = 0.006), respectively. However, after correction for age, gender, MAP and diabetes mellitus, this relation lost statistical significance.Conclusions. In a dialysis population with a relatively low level of inflammatory activity, the soluble calcification inhibitor fetuin-A could not be identified as an independent predictor of aortic stiffness as measured with PWV and AI. [ABSTRACT FROM AUTHOR]

Background. Preoperative assessment of forearm superficial venous diameter may predict early failure of newly created arteriovenous fistulas for haemodialysis access. However, early failure and non-maturation rates remain high (up to 30%) and reported cut-off diameters are inconsistent. We hypothesize that this inconsistency is due to differences in the methods used to achieve venous dilatation prior to diameter measurements and daily variation in superficial venous diameter. We furthermore hypothesize that the use of a cuff will lead to a better inter-observer agreement since the applied pressure can be precisely determined. The purpose of this study was to determine inter-observer agreement of superficial venous diameter measurement under venous congestion by using either a graduated pressure cuff or tourniquet and furthermore, to determine daily variations in superficial venous diameter.Methods. Diameter measurements were performed by two observers on days 1 and 3, in 21 end-stage renal disease patients using either a cuff (60 mmHg) or tourniquet. Measurements were carried out in random order and observers were blinded for each other''s results. Inter-observer agreement was expressed as interclass correlation coefficients. Variance components analysis was used to determine possible causes of disagreement.Results. Using a cuff, mean venous diameter was 1.8 mm (range, 0.7–3.3 mm). When a tourniquet was used, the mean diameter was 1.8 mm (range, 0.6–3.2 mm). Interclass correlation coefficients between observers were 0.76 and 0.74 for the use of a cuff and tourniquet, respectively. Diameter measurements were revealed to be observer independent. Variations in venous diameter were determined by the patient and the interaction of patient and day. Repeated assessment of venous diameter on different days revealed a variation coefficient of 26.4% when using a cuff, and 26.5% when using a tourniquet.Conclusions. Venous diameter assessment is observer and congestion method independent. Daily variations in forearm superficial venous diameters should be taken into account when defining and using cut-off diameters prior to vascular access surgery. [ABSTRACT FROM AUTHOR]

Background. According to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) and the European Guidelines, the first and second choice for vascular access for haemodialysis are the radial–cephalic and brachial–cephalic arteriovenous fistula (AVF). Autogenous fistulas have a longer functional lifetime, less thrombotic complications and a lower infection risk compared with prosthetic implants. If it is impossible to create a brachial–cephalic AVF or after failure, either a brachial–basilic (BB) or a prosthetic forearm loop AVF may be considered. To determine the outcome of BB-AVFs, we retrospectively surveyed the results of this type of vascular access.Methods. All BB-AVF patient records over a 6 year period were subtracted from an academic hospital registry. Primary failure and primary, assisted primary and secondary patency rates were calculated with the Kaplan–Meier method. Sex, diabetes mellitus (DM), pre-operative duplex diameters, complications and interventions were recorded and correlated with the patency rates.Results. A total of 31 BB-AVFs were created in a one-stage surgical procedure. Of the patients, 36% were male and 19% had DM. Only one patient had a primary failure, leaving 30 (97%) of the BB-AVFs functional for dialysis treatment. Four patients died within 1 year after the operation, one of them from a catheter sepsis. Primary, assisted primary and secondary patency rates after 1 year were, 58, 83 and 90%, respectively. Patient characteristics and pre-operative duplex parameters did not influence patency rates.Conclusion. The BB-AVF is an excellent third choice option for vascular access. [ABSTRACT FROM AUTHOR]