Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50-84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: ß=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher loge (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters.

Assessment of energy requirement for the retinal arterial network in normal and hypertensive subjects.

The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement.

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease.

AIMS/HYPOTHESIS: A high prevalence of diabetes contributes to excess CHD in Indian Asians, but the underlying mechanisms are unclear. Heart rate, heart rate variability (HRV) and baroreflex sensitivity (BRS) are measures of cardiac autonomic function that are disturbed by hyperglycaemia and predict CHD. We compared these measures in Indian Asians and Europeans, and sought explanations for the observed differences. METHODS: A representative sample of 149 Europeans and 151 Indian Asians was recruited from primary care, 66% of them men (aged 35-75 years), 34% women (aged 55-75 years). Heart rate, HRV, BRS and cardio-metabolic profiles were measured over four successive 5 min periods with continuous ECG and blood pressure monitoring. RESULTS: Indian Asians were hyperglycaemic compared with Europeans (HbA(1c) (mean +/- SD) 6.5 +/- 1.2% vs 5.9 +/- 1.0%, p = 0.001). They had shorter mean RR intervals ((mean +/- SE) 969 +/- 13 vs 1,022 +/- 12 ms, p = 0.002), lower total RR interval power ((geometric mean, 95% CI) 925 [796-1075] vs 1,224 [1,064-1,422] ms(2), p = 0.008) and lower BRS ((mean +/- SE) 5.7 +/- 1.0 vs 6.6 +/- 1.0 ms/mmHg, p = 0.01). All measures of cardiac autonomic dysfunction were significantly associated with hyperglycaemia (mean RR interval vs HbA(1c) r = -0.22; p < 0.001). Ethnic differences in cardiac autonomic function persisted after adjustment for age, blood pressure and medication (mean RR interval 973 vs 1,021 ms, p = 0.004), but were attenuated or abolished by adjusting for HbA(1c) (979 vs 1,014 ms, p = 0.06) or other markers of hyperglycaemia. CONCLUSIONS/INTERPRETATION: Indian Asians from the general population have impaired cardiovascular autonomic function compared with Europeans. This is due to greater hyperglycaemia in Indian Asians and may determine their increased CHD risk.

Computational analysis of oxygen transport in the retinal arterial network.

PURPOSE: The retina has a high oxygen consumption, making it particularly vulnerable to vascular insults, impairing oxygen and nutrient supply. The aim of this study was to develop a detailed computational model for quantitative analysis of blood flow and oxygen transport in physiologically realistic retinal arterial networks. Such a model will allow us to examine the effect of topological changes in retinal vasculature on hemodynamics and oxygen distribution in the retinal circulation. MATERIALS AND METHODS: The Navier-Stokes equations for blood flow and the convection-diffusion equation for oxygen transfer were solved numerically to obtain detailed blood flow and oxygen distribution patterns in a retinal arterial tree. The geometrical outlines of the central retinal artery and its major branches were extracted from retinal images acquired from a healthy young adult by a Zeiss FF450+ fundus camera. The reconstructed subject-specific retinal arterial network geometry was combined with a structured tree model for the distal peripheral vessels. The non-Newtonian rheological properties of blood were incorporated by using an empirical viscosity model to account for the Fahraeus-Lindqvist effect. RESULTS: The model predicted pressure drops in the range of 11-14.6 mmHg between the inlet and outlets of the reconstructed network and non-uniform oxygen tension, which varied with the vessel diameter and distance from the optic disc. The mean oxygen saturation in retinal arteries was 93.1% for vessels larger than 50 mum in diameter and 82.2% for smaller arterioles. CONCLUSIONS: Our numerical results are in good agreement with in vivo measurements reported in the literature, demonstrating the potential of our model for prediction of oxygen distribution and intravascular oxygen tension profiles in the retinal arterial network. This paves the way for investigating the effects of parameter variation, simulating cases not available from experimental studies.

Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 x 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril-indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA(1c) of < or = 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of > or =2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome. RESULTS: Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57-1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29-0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38-0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61-1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere. CONCLUSIONS/INTERPRETATION: Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions. TRIAL REGISTRATION: ClinicalTrials.gov ID no. NCT00145925. FUNDING: Grants from Servier and the National Health and Medical Research Council of Australia.

Computational analysis of oxygen transport in a patient-specific model of abdominal aortic aneurysm with intraluminal thrombus.

Abdominal aortic aneurysm (AAA) is a degenerative disease in which the afflicted person suffers from a localised dilatation of the abdominal aorta. Intraluminal thrombus (ILT), which is present in approximately 75% of all AAAs, plays an important role in the progression of the disease. It has been suggested that ILT may attenuate oxygen diffusion to the aortic wall, resulting in further degeneration and weakening of the wall. Previous numerical studies using idealised AAA models have shown the effect of ILT thickness on oxygen diffusion, but patient-specific studies of oxygen transport incorporating convection, diffusion and reaction from the lumen to AAA wall are lacking. In the present study, a coupled fluid-thrombus-wall model was developed to simulate oxygen transport in a patient-specific AAA containing ILT. Blood flow in the lumen was governed by the Navier-Stokes equations and oxygen transfer was described by the convection-diffusion equation in the lumen, diffusion equation in the thrombus, and diffusion-reaction equation in the wall. A parametric study was performed to evaluate the sensitivity of numerical predictions to oxygen diffusivity in ILT and adventitial oxygen concentration. The results not only provide further support to previous findings that the presence of ILT may significantly impair oxygen transfer from blood to the aortic wall, but also demonstrate that adventitial oxygen concentration has a profound effect on oxygen concentration in the wall, and that the oxygen supply from the lumen to the wall can be reduced by 80% if the ILT thickness is greater than 5 mm.

The effect of dynamic vessel motion on haemodynamic parameters in the right coronary artery: a combined MR and CFD study.

Human right coronary artery (RCA) haemodynamics is investigated using computational fluid dynamics (CFD) based on subject-specific information from magnetic resonance (MR) acquisitions. The dynamically varying vascular geometry is reconstructed from MR images, incorporated in CFD in conjunction with pulsatile flow conditions obtained from MR velocity mapping performed on the same subject. The effects of dynamic vessel motion on instantaneous and cycle-averaged haemodynamic parameters, such as wall shear stress (WSS), time-averaged WSS (TAWSS) and oscillatory shear index (OSI), are examined by comparing an RCA model with a time-varying geometry and those with a static geometry, corresponding to nine different time-points in the cardiac cycle. The results show that the TAWSS is similar for the dynamic and static wall models, both qualitatively and quantitatively (correlation coefficient 0.89-0.95). Conversely, the OSI shows much poorer correlations (correlation coefficient 0.38-0.60), with the best correspondence being observed with the static models constructed from images acquired in late diastole (at t = 0 and 800 ms, the cardiac cycle is 900 ms). These findings suggest that neglecting dynamic motion of the RCA is acceptable if TAWSS is the primary focus but may result in underestimation of haemodynamic parameters related to the oscillatory nature of the blood flow.

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

BACKGROUND: Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. METHODS: Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. RESULTS: Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. CONCLUSIONS: Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

Analysis of complex flow and the relationship between blood pressure, wall shear stress, and intima-media thickness in the human carotid artery.

BACKGROUND: Previous clinical studies have observed relationships between increased intima-media thickness (IMT) in the carotid artery, elevated blood pressure, and low wall shear stress (WSS) calculated from the Poiseuille equation. This study used numerical methods to more accurately determine WSS in the carotid artery and to investigate possible determinants of increased IMT. METHODS: IMT [common carotid artery (CCA) and bulb], CCA flow velocity, brachial systolic (SBP) and diastolic blood pressure (DBP), and carotid systolic pressure (cSBP) were measured in 14 healthy subjects (aged 44 +/- 16 yr). Flow patterns in the carotid bifurcation were determined by computational fluid dynamics (CFD) based on three-dimensional ultrasound geometry. Instantaneous and time-averaged wall shear stress (WSS(av)), oscillatory shear index (OSI), and wall shear stress angle gradients (WSSAG) were calculated. RESULTS: IMT was positively related to SBP, DBP, cSBP, and WSSAG and inversely related to WSS(av) in the CCA. In the bulb, IMT was positively related to SBP and cSBP but was not significantly related to WSS(av) or WSSAG. IMT was unrelated to OSI in both the CCA and the bulb. CONCLUSION: Increased carotid artery IMT in healthy subjects with no evidence of focal plaques is primarily a response to elevated pressure.

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. MATERIALS AND METHODS: A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. RESULTS: Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. CONCLUSION: The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.

Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease.

Atherosclerosis in the superficial femoral artery (SFA) resulting in peripheral arterial disease is more common in men than women and shows a predilection for the region of the adductor canal. Blood flow patterns are related to development of atherosclerosis, and we investigated if curvature and tortuosity of the femoral artery differed between young men and women and if differences resulted in adverse flow patterns. Magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) were combined in 18 young adult volunteers (9 men) to assess the relationship of flow features to likely sites of future atherosclerosis formation. Subjects underwent MRI of the right SFA, three-dimensional vascular geometry was reconstructed, and measures of tortuosity and curvature were calculated. Tortuosity and curvature were significantly greater for men than women, and this was related to increased body surface area, body mass index, or weight in men. In both sexes, "tortuosity" increased from the midthigh to the popliteal fossa. The greatest curvature was found within the distal quarter of the SFA. CFD modeling was undertaken on MRI-based reconstructions of the SFA. Wall shear stresses (WSS) were extracted from the computations. WSS showed greater spatial variation in the men than in the women, and the men exhibited lower mean WSS. These data indicate that sex differences related to body size and anatomical course of the femoral artery may contribute to the enhanced risk of focal atherosclerosis in the adductor canal.

Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive approach using wave-intensity analysis.

The study of wave propagation at different points in the arterial circulation may provide useful information regarding ventriculoarterial interactions. We describe a number of hemodynamic parameters in the carotid, brachial, and radial arteries of normal subjects by using noninvasive techniques and wave-intensity analysis (WIA). Twenty-one normal adult subjects (14 men and 7 women, mean age 44 +/- 6 yr) underwent applanation tonometry and pulsed-wave Doppler studies of the right common carotid, brachial, and radial arteries. After ensemble averaging of the pressure and flow-velocity data, local hydraulic work was determined and a pressure-flow velocity loop was used to determine local wave speed. WIA was then applied to determine the magnitude, timings, and energies of individual waves. At all sites, forward-traveling (S) and backward-traveling (R) compression waves were observed in early systole. In mid- and late systole, forward-traveling expansion waves (X and D) were also seen. Wave speed was significantly higher in the brachial (6.97 +/- 0.58 m/s) and radial (6.78 +/- 0.62 m/s) arteries compared with the carotid artery (5.40 +/- 0.34 m/s; P < 0.05). S-wave energy was greatest in the brachial artery (993.5 +/- 87.8 mJ/m2), but R-wave energy was greatest in the radial artery (176.9 +/- 19.9 mJ/m2). X-wave energy was significantly higher in the brachial and radial arteries (176.4 +/- 32.7 and 163.2 +/- 30.5 mJ/m2, respectively) compared with the carotid artery (41.0 +/- 9.4 mJ/m2; P < 0.001). WIA illustrates important differences in wave patterns between peripheral arteries and may provide a method for understanding ventriculo-arterial interactions in the time domain.

Influence of head position on carotid hemodynamics in young adults.

Studies in adults have shown marked changes in geometry and relative positions of the carotid arteries when rotating the head. The aim of this study was to quantify the change in geometry and analyze its effect on carotid hemodynamics as a result of head rotation. The right carotid arteries of nine young adult subjects were investigated in supine position with straight and left turned head positions, respectively. The three-dimensional (3D) carotid geometry was reconstructed by using 3D ultrasound (3D US), and the carotid hemodynamics were calculated by combining 3D US with computational fluid dynamics. It was observed that cross-sectional areas and shapes did not change markedly with head rotation, but carotid vessel center lines altered with planarification of the common carotid artery as a main feature (P < 0.05). Measured common carotid flow rates changed significantly at the individual level when the head was turned, but on the average, the change in mean common carotid flow rate was relatively small (0.37 +/- 1.11 ml/s). The effect of the altered center lines and flow rates on the atherogenic nature of the carotid bifurcation was evaluated by using calculated hemodynamic wall parameters, such as wall shear stress (WSS) and oscillatory shear index (OSI). It was found that WSS and OSI patterns changed significantly with head rotation, but the variations were very subject dependent and could not have been predicted without assessing the altered geometry and flow of the carotid bifurcation for individual cases. This study suggests that there is a need for standardization of the choice of head position in the 3D US scan protocol, and that carotid stents and emboli diverters should be studied in different head positions.

The integration of medical imaging and computational fluid dynamics for measuring wall shear stress in carotid arteries.

The link between atherosclerosis and wall shear stress (WSS) has lead to considerable interest in the in vivo estimation of WSS. Both magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS) are capable of providing the anatomical and flow data required for subject-specific computational fluid dynamics (CFD) simulations. This study compares, for the first time, predicted 3D flow patterns based on black blood MRI and 3DUS. Velocity fields in the carotid arteries of nine subjects have been reconstructed, and the haemodynamic wall parameters WSS, oscillatory shear index (OSI), WSS gradients (WSSG) and angle gradients (WSSAG) were computed and compared. There was a good qualitative agreement between results derived from MRI and 3DUS, embodied by a strong linear correlation between the patched representations of the haemodynamic wall parameters. The root-mean-square error between haemodynamic wall parameters was comparable to the range of the expected variability of each imaging technique (WSS: 0.411 N/m; OSI: 0.048; temporal WSSG: 2.29 N/(s.m/sup 2/); spatial WSSG: 150 N/m/sup 3/; WSSAG: 87.6 rad/m). In conclusion, MRI and 3DUS are comparable techniques for combining with CFD in the carotid artery. The relatively high cost of MRI favour 3DUS to MRI for future haemodynamic studies of superficial arteries.

Flow patterns and wall shear stresses in patient-specific models of the abdominal aortic aneurysm.

Abdominal Aortic Aneurysms (AAAs) are a major cause of death in Western societies. However, the factors responsible for the growth and ultimate rupture of AAA are not fully understood. Using computation fluid dynamics combined with CT images, the flow patterns and wall shear stress (WSS) in the AAA of a patient were studied. AAA geometry was obtained from images acquired during a routine CT scan, and a realistic abdominal aortic flow waveform was used as an upstream boundary condition. The computational results showed the presence of multiple flow recirculation zones and overall low WSS in the bulge of the aneurysm. This may provide some insight into the growth of thrombus in AAA.

Image-based carotid flow reconstruction: a comparison between MRI and ultrasound.

Atherosclerosis is a major cause of morbidity and mortality. Its apparent link with wall shear stress (WSS) has led to considerable interest in the in vivo estimation of WSS. Determining WSS by combining medical images with computational fluid dynamics (CFD) simulations can be performed both with magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS). This study compares predicted 3D flow patterns based on black blood MRI and 3DUS. Velocity fields in the carotid arteries of nine subjects have been reconstructed, and the haemodynamic wall parameters WSS, oscillatory shear index (OSI), WSS gradients (WSSG) and angle gradients (WSSAG) were compared between the two imaging techniques. There was a good qualitative agreement between results derived from MRI and 3DUS (average correlation strength above 0.60). The root mean square error between haemodynamic wall parameters was comparable to the range of the expected variability of each imaging technique (WSS: 0.411 N m(-2); OSI: 0.048; temporal WSSG: 150 N s(-1) m(-2); spatial WSSG: 2.29 N m(-3); WSSAG: 87.6 rad m(-1)). In conclusion, MRI and 3DUS are capable of providing haemodynamic parameters when combined with CFD, and the predictions are in most cases qualitatively and quantitatively similar. The relatively high cost of MRI and continuing improvement in ultrasound favour US to MRI for future haemodynamic studies of superficial arteries.

Various issues relating to computational fluid dynamics simulations of carotid bifurcation flow based on models reconstructed from three-dimensional ultrasound images.

Computational fluid dynamics (CFD) flow simulation techniques have the potential to enhance understanding of how haemodynamic factors are involved in atherosclerosis. Recently, three-dimensional ultrasound has emerged as an alternative to other three-dimensional imaging techniques, such as magnetic resonance angiography (MRA). The method can be used to generate accurate vascular geometry suitable for CFD simulations and can be coupled with Doppler ultrasound to provide physiologically realistic flow boundary conditions. However, there are various ways to utilize the flow data acquired, possibly leading to different results regarding both flow and wall shear stress patterns. A disadvantage of three-dimensional ultrasound for imaging the carotid bifurcation has been established as being the scanning limitation of the jawbone position. This may make artificial extensions of the internal and/or external carotid arteries necessary, which in turn may influence the predicted flow patterns. Flow simulations were carried out for three outflow calculation schemes as well as four geometries with different extensions to the carotid daughter vessels. It was found that variation of flow patterns was more strongly influenced by the outflow conditions than by the extensions of the daughter vessels. Consequently, it is recommended that for future CFD simulations of carotid flow using three-dimensional ultrasound data, the outflow boundary conditions should rely on the most accurate measurement available, and flow data recorded in the common and internal carotid are considered more reliable than data from the external carotid. Even though the extended lengths of the daughter vessels have insignificant effects on the predicted haemodynamic parameters, it would be a safer option to extend the internal carotid by approximately three times the diameter of the common carotid artery.

Carotid angioplasty in a pulsatile flow model: factors affecting embolic potential.

OBJECTIVES: Carotid endoluminal intervention is an alternative to surgery but carries a risk of embolic stroke even with distal protection devices. We investigated the clinical features and degree of stenosis related to number and size of emboli during carotid angioplasty. DESIGN: An experimental ex vivo study. MATERIALS: An ex vivo pulsatile flow model was used in which temperature, velocity, flow, pressure and viscosity characteristics were designed to simulate the carotid circulation. METHODS: Carotid endarterectomy specimens excised as intact cylinders (n = 28) were subjected to a standardised angioplasty procedure using radiological guidance. Emboli collected in filters placed distally were counted and sized using microscopy. RESULTS: Median number of emboli during angioplasty was 133 (range 15-1331). Median size of the largest embolus was 700 microns (range 75-2400). Severity of stenosis correlated with increased maximum size (r = 0.55, p = 0.012). Statin therapy >4 weeks pre-operatively was associated with reduced emboli number and size (54 (range 15-748) vs 247 (range 37-1331) [p = 0.023] and 400 microm (range 75-2400) vs 1300 microm (range 600-2200) [p = 0.022]). CONCLUSIONS: In this model a wide range of emboli number and size were produced. Number and size of embolic particles were highest in patients with high-grade stenoses not receiving statin therapy.

Accuracy and reproducibility of CFD predicted wall shear stress using 3D ultrasound images.

Computational fluid dynamics (CFD) flow simulation techniques have the potential to enhance our understanding of how haemodynamic factors are involved in atherosclerosis. Recently, 3D ultrasound has emerged as an alternative to other 3D imaging techniques, such as magnetic resonance angiography (MRA). The method can be used to generate realistic vascular geometry suitable for CFD simulations. In order to assess accuracy and reproducibility of the procedure from image acquisition to reconstruction to CFD simulation, a human carotid artery bifurcation phantom was scanned three times using 3D ultrasound. The geometry was reconstructed and flow simulations were carried out on the three sets as well as on a model generated using computer aided design (CAD) from the geometric information given by the manufacturer. It was found that the three reconstructed sets showed good reproducibility as well as satisfactory quantitative agreement with the CAD model. Analyzing two selected locations probably representing the 'worst cases,' accuracy comparing ultrasound and CAD reconstructed models was estimated to be between 7.2% and 7.7% of the maximum instantaneous WSS and reproducibility comparing the three scans to be between 8.2% and 10.7% of their average maximum.

Effect of tumour necrosis factor-alpha and interleukin 1beta on endothelium-dependent relaxation in rat mesenteric resistance arteries in vitro.

1. Pre-eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) on endothelium-dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro. 2. Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K(80)). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium-independent relaxant. Inhibition of NO synthase by a combination of N(omega)-monomethyl-L-arginine (L-NMMA) and N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L-NMMA and L-NAME. Inhibition of endothelium-derived hyperpolarizing factor (EDHF) by K(80) partially reduced responses to ACH and BK. Inhibition of HIS-induced relaxation was more marked with K(80). L-NMMA and L-NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K(80). 3. Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH-induced relaxation in arteries contracted with K(80). IL-1 had no effect on responses to ACH and the combination of TNF and IL-1 was not more effective than TNF alone. 4. The inhibitory effect of TNF on ACH-induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L-NMMA and L-NAME. 5. TNF inhibits the NO-dependent component of endothelium-dependent relaxation in response to ACH and BK, but does not inhibit the EDHF-dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O(2)(-)) and the ability of O(2)(-) to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre-eclampsia.