Common carotid wall shear stress and carotid atherosclerosis in end-stage renal disease patients

Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349+/-148 vs. 506+/-206 s(-1), p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= -0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects.     

Noninvasive determination of spatial distribution and temporal gradient of wall shear stress at common carotid artery

Wall shear stress (WSS) has been proved to play a critical role in formation and development of atherosclerotic plaques. Our objective was to quantify local WSS in vivo in normal subjects, and to analyze spatial distribution patterns and determine the temporal gradient of WSS. Seventy-eight CCAs of 42 healthy volunteers at common carotid arteries (CCAs) were studied. Cine phase-contrast MR sequence was used to acquire the flow velocity information. Three-dimensional paraboloid modeling was applied to fit the velocity profiles and WSS values were calculated. Mean WSS value for CCAs was 0.783+/-0.209, with the range of WSS value from -0.541 to 3.464 N/m(2). The 95% confidence interval for mean WSS value in CCA was (0.736-0.830) N/m(2). Different WSS spatial distribution patterns were classified into three types according to the location of low WSS values during a cardiac cycle. Mean value of maximum temporal gradient of WSS was 14.12+/-5.46, with the range from 5.87 to 33.23 N/m(2)s(-1). Skewed velocity profiles were displayed in most CCAs, indicating the flow patterns in CCA were more complicated than commonly assumed. Obvious inter-subject variation were found in magnitude, spatial distribution and the temporal gradient of WSS in CCAs, and the blood flow patterns as well.     

Hemodynamics and wall mechanics in human carotid bifurcation and its consequences for atherogenesis: investigation of inter-individual variation

Finite element simulations of fluid-solid interactions were used to investigate inter-individual variations in flow dynamics and wall mechanics at the carotid artery bifurcation, and its effects on atherogenesis, in three healthy humans (normal volunteers: NV1, NV2, NV4). Subject-specific calculations were based on MR images of structural anatomy and ultrasound measurements of flow at domain boundaries. For all subjects, the largest contiguous region of low wall shear stress (WSS) occurred at the carotid bulb, WSS was high (6-10 Pa) at the apex, and a small localized region of WSS > 10 Pa occurred close to the inner wall of the external carotid artery (ECA). NV2 and NV4 had a "spot" of low WSS distal to the bifurcation at the inner wall of the ECA. Low WSS patches in the common carotid artery (CCA) were contiguous with the carotid bulb low WSS region in NV1 and NV2, but not in NV4. In all three subjects, areas of high oscillatory shear index (OSI) were confined to regions of low WSS. Only NV4 exhibited high levels of OSI on the external adjoining wall of the ECA and CCA. For all subjects, the maximum wall shear stress temporal gradient (WSSTG) was highest at the flow divider (reaching 1,000 Pa/s), exceeding 300 Pa/s at the walls connecting the ECA and CCA, but remaining below 250 Pa/s outside of the ECA. In all subjects, (maximum principle) cyclic strain (CS) was greatest at the apex (NV1: 14%; NV2: 11%; NV4: 6%), and a second high CS region occurred at the ECA-CCA adjoining wall (NV1: 11%, NV2: 9%, NV4: 5%). Wall deformability was included in one simulation (NV2) to verify that it had little influence on the parameters studied. Location and magnitude of low WSS were similar, except for the apex (differences of up to 25%). Wall distensibility also influenced OSI, doubling it in most of the CCA, separating the single high OSI region of the carotid bulb into two smaller regions, and shrinking the ECA internal and external walls' high OSI regions. These observations provide further evidence that significant intra-subject variability exists in those factors thought to impact atherosclerosis.     

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.     

Correlation between quantitative analysis of wall shear stress and intima-media thickness in atherosclerosis development in carotid arteries

Background

This paper presents quantitative analysis of blood flow shear stress by measuring the carotid arterial wall shear stress (WSS) and the intima-media thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly basis in order to cause atherosclerosis.

Methods

This study is based on establishing an atherosclerosis model of high-fat rabbits, and measuring the rabbits’ common carotid arterial WSS of the experimental group and control group on a weekly basis. Detailed analysis was performed by using WSS quantification.

Results

We have demonstrated small significant difference of rabbit carotid artery WSS between the experimental group and the control group (P<0.01) from the 1st week onwards, while the IMT of experimental group had larger differences from 5th week compared with the control group (P<0.05). Next, we have shown that with increasing blood lipids, the rabbit carotid artery shear stress decreases and the rabbit carotid artery IMT goes up. The decrease of shear stress appears before the start of IMT growth. Furthermore, our receiver operator characteristic (ROC) curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm², the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and the specificity is 81.3%. The area under the ROC curve is 0.9283.

Conclusions

All these data goes to show that WSS decreasing to 1.198 dyne/cm² can be used as an indicator that rabbit common carotid artery comes into the period of fibrous plaques. In conclusion, our study is able to find and confirm that the decrease of the arterial WSS can predict the occurrence of atherosclerosis earlier, and offer help for positive clinical intervention.

     

Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.     

Effects of posture on shear rates in human brachial and superficial femoral arteries

Shear rate is significantly lower in the superficial femoral compared with the brachial artery in the supine posture. The relative shear rates in these arteries of subjects in the upright posture (seated and/or standing) are unknown. The purpose of this investigation was to test the hypothesis that upright posture (seated and/or standing) would produce greater shear rates in the superficial femoral compared with the brachial artery. To test this hypothesis, Doppler ultrasound was used to measure mean blood velocity (MBV) and diameter in the brachial and superficial femoral arteries of 21 healthy subjects after being in the supine, seated, and standing postures for 10 min. MBV was significantly higher in the brachial compared with the superficial femoral artery during upright postures. Superficial femoral artery diameter was significantly larger than brachial artery diameter. However, posture had no significant effect on either brachial or superficial femoral artery diameter. The calculated shear rate was significantly greater in the brachial (73 +/- 5, 91 +/- 11, and 97 +/- 13 s(-1)) compared with the superficial femoral (53 +/- 4, 39 +/- 77, and 44 +/- 5 s(-1)) artery in the supine, seated, and standing postures, respectively. Contrary to our hypothesis, our current findings indicate that mean shear rate is lower in the superficial femoral compared with the brachial artery in the supine, seated, and standing postures. These findings of lower shear rates in the superficial femoral artery may be one mechanism for the higher propensity for atherosclerosis in the arteries of the leg than of the arm.     

Influence of the Accuracy of Angiography-Based Reconstructions on Velocity and Wall Shear Stress Computations in Coronary Bifurcations: A Phantom Study

Introduction

Wall shear stress (WSS) plays a key role in the onset and progression of atherosclerosis in human coronary arteries. Especially sites with low and oscillating WSS near bifurcations have a higher propensity to develop atherosclerosis. WSS computations in coronary bifurcations can be performed in angiography-based 3D reconstructions. It is essential to evaluate how reconstruction errors influence WSS computations in mildly-diseased coronary bifurcations. In mildly-diseased lesions WSS could potentially provide more insight in plaque progression.

Materials Methods

Four Plexiglas phantom models of coronary bifurcations were imaged with bi-plane angiography. The lumens were segmented by two clinically experienced readers. Based on the segmentations 3D models were generated. This resulted in three models per phantom: one gold-standard from the phantom model itself, and one from each reader. Steady-state and transient simulations were performed with computational fluid dynamics to compute the WSS. A similarity index and a noninferiority test were used to compare the WSS in the phantoms and their reconstructions. The margin for this test was based on the resolution constraints of angiography.

Results

The reconstruction errors were similar to previously reported data; in seven out of eight reconstructions less than 0.10 mm. WSS in the regions proximal and far distal of the stenosis showed a good agreement. However, the low WSS areas directly distal of the stenosis showed some disagreement between the phantoms and the readers. This was due to small deviations in the reconstruction of the stenosis that caused differences in the resulting jet, and consequently the size and location of the low WSS area.

Discussion

This study showed that WSS can accurately be computed within angiography-based 3D reconstructions of coronary arteries with early stage atherosclerosis. Qualitatively, there was a good agreement between the phantoms and the readers. Quantitatively, the low WSS regions directly distal to the stenosis were sensitive to small reconstruction errors.     

Flow patterns and wall shear stress distribution in human internal carotid arteries: the geometric effect on the risk for stenoses

It has been widely observed that atherosclerotic stenosis occurs at sites with complex hemodynamics, such as arteries with high curvature or bifurcations. These regions usually have very low or highly oscillatory wall shear stress (WSS). In the present study, 3D sinusoidally pulsatile blood flow through the models of internal carotid artery (ICA) with different geometries was investigated with computational simulation. Three preferred sites of stenoses were found along the carotid siphon with low and highly oscillatory WSS. The risk for stenoses at these sites was scaled with the values of time-averaged WSS and oscillating shear index (OSI). The local risk for stenoses at every preferred site of stenoses was found different between 3 types of ICA, indicating that the geometry of the blood vessel plays significant roles in the atherogenesis. Specifically, the large curvature and planarity of the vessel were found to increase the risk for stenoses, because they tend to lower WSS and elevate OSI. Therefore, the geometric study makes it possible to estimate the stenosis location in the ICA siphon as long as the shape of ICA was measured.     

Intimal hyperplasia and wall shear in arterial bypass graft distal anastomoses: an in vivo model study

The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.     

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.     

beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes

The effect of beta antagonists in the diabetic vascular lesion is controversial. We investigated the effect of celiprolol hydrochloride, a beta1 antagonist and mild beta2 agonist, on the lesions and function in type II male Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats. OLETF rats were fed regular chow with or without atenolol (25 mg/kg/day) or celiprolol (100 mg/kg/day) treatment (group DM, no treatment; group DM-a, atenolol treatment; group DM-c, celiprolol treatment), and treatment was continued for 31 days. Separately, normoglycemic control rats, LETO, were prepared as group C. On day 3, endothelial cells of the right internal carotid artery were removed by balloon injury, and the rats were evaluated 4 weeks after balloon injury. The plasma glucose and lipid levels were unchanged throughout the treatment period. Intimal thickening was observed in the right carotid artery in the DM and DM-a groups; however, little thickening was observed in those of DM-c rats. Acetylcholine-induced NO-dependent relaxation in arteries was improved in DM-c rats compared with DM and DM-a rats (maximum relaxation DM 30.8+/-4.5, DM-a 37.4+/-3.9, DM-c 48.8+/-4.6%, *P<0.05 vs. DM for DM-c rats). Tone-related basal NO release and acetylcholine-induced NO-dependent relaxation in the arteries and plasma NO(x) (sum of NO(2)(-) and NO(3)(-)) were greater in DM-c and C groups than in DM and DM-a groups. The serum TNFalpha levels did not increase in DM-c rats compared with those of the DM or DM-a groups, and were comparable with those of group C. CONCLUSION: In conclusion, Celiprolol improves endothelial function in the arteries of OLETF rats, and further restore it 4 weeks after endothelial denudation in the arteries of OLETF rats. NO and O(2)(-) may have a role in the important underlying mechanisms by reducing the TNFalpha levels.     

MRI-based quantification of outflow boundary conditions for computational fluid dynamics of stenosed human carotid arteries

Accurate assessment of wall shear stress (WSS) is vital for studies on the pathogenesis of atherosclerosis. WSS distributions can be obtained by computational fluid dynamics (CFD) using patient-specific geometries and flow measurements. If patient-specific flow measurements are unavailable, in- and outflow have to be estimated, for instance by using Murray’s Law. It is currently unknown to what extent this law holds for carotid bifurcations, especially in cases where stenoses are involved. We performed flow measurements in the carotid bifurcation using phase-contrast MRI in patients with varying degrees of stenosis. An empirical relation between outflow and degree of area stenosis was determined and the outflow measurements were compared to estimations based on Murray’s Law. Furthermore, the influence of outflow conditions on the WSS distribution was studied.For bifurcations with an area stenosis smaller than 65%, the outflow ratio of the internal carotid artery (ICA) to the common carotid artery (CCA) was 0.62±0.12 while the outflow ratio of the external carotid artery (ECA) was 0.35±0.13. If the area stenosis was larger than 65%, the flow to the ICA decreased linearly to zero at 100% area stenosis. The empirical relation fitted the flow data well (R²=0.69), whereas Murray’s Law overestimated the flow to the ICA substantially for larger stenosis, resulting in an overestimation of the WSS. If patient-specific flow measurements of the carotid bifurcation are unavailable, estimation of the outflow ratio by the presented empirical relation will result in a good approximation of calculated WSS using CFD.     

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.     

Numerical simulation of pulsatile flow in a compliant curved tube model of a coronary artery

The endothelial cells (ECs) lining a blood vessel wall are exposed to both the wall shear stress (WSS) of blood flow and the circumferential strain (CS) of pulsing artery wall motion. These two forces and their interaction are believed to play a role in determining remodeling of the vessel wall and development of arterial disease (atherosclerosis). This study focused on the WSS and CS dynamic behavior in a compliant model of a coronary artery taking into account the curvature of the bending artery and physiological radial wall motion. A three-dimensional finite element model with transient flow and moving boundaries was set up to simulate pulsatile flow with physiological pressure and flow wave forms characteristic of the coronary arteries. The characteristic coronary artery curvature and flow conditions applied to the simulation were: aspect ratio (lambda) = 10, diameter variation (DV) = 6 percent, mean Reynolds number (Re) = 150, and unsteadiness parameter (alpha) = 3. The results show that mean WSS is about 50 percent lower on the inside wall than the outside wall while WSS oscillation is stronger on the inside wall. The stress phase angle (SPA) between CS and WSS, which characterizes the dynamics of the mechanical force pattern applied to the endothelial cell layer, shows that CS and WSS are more out of phase in the coronaries than in any other region of the circulation (-220 deg on the outside wall, -250 deg on the inside wall). This suggests that in addition to WSS, SPA may play a role in localization of coronary atherosclerosis.     

Contribution of nitric oxide to cutaneous microvascular dilation in individuals with type 2 diabetes mellitus

Microvascular pathophysiology associated with type 2 diabetes mellitus (T2DM) contributes to several aspects of the morbidity associated with the disease. We quantified the contribution of nitric oxide (NO) to the cutaneous vasodilator response to nonpainful local warming in subjects with T2DM (average duration of diabetes mellitus 7 +/- 1 yr) and in age-matched control subjects. We measured skin blood flow in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or vehicle during 35 min of local warming to 42 degrees C. Microdialysis of sodium nitroprusside (SNP) was used for assessment of maximum cutaneous vascular conductance (CVC). Resting CVC was higher in T2DM subjects at vehicle sites (T2DM: 19 +/- 2 vs. control: 11 +/- 3%maxCVC; P < 0.05); this difference was abolished by l-NAME (T2DM: 10 +/- 1 vs. control: 8 +/- 1%maxCVC; P > 0.05). The relative contribution of NO to the vasodilator response to local warming was not different between groups (T2DM: 46 +/- 4 vs. control: 44 +/- 6%maxCVC; P > 0.05). However, absolute CVC during local warming was approximately 25% lower in T2DM subjects (T2DM: 1.79 +/- 0.15 AU/mmHg; controls: 2.42 +/- 0.20 AU/mmHg; P < 0.01), and absolute CVC during SNP was approximately 20% lower (T2DM: 1.91 +/- 0.12 vs. control: 2.38 +/- 0.13 AU/mmHg; P < 0.01). We conclude that the relative contribution of NO to vasodilation during local warming is similar between subjects with T2DM and control subjects, although T2DM was associated with a lower absolute maximum vasodilation.     

Arterial properties of the carotid and femoral artery in endurance-trained and paraplegic subjects.

In humans, the relationships of blood flow changes to structure, function, and shear rate of conducting arteries have not been thoroughly examined. Therefore, the purpose of this study was to investigate these parameters of the elastic-type, common carotid artery (CCA) and the muscular-type, common femoral artery (CFA) in long-term highly active and extremely inactive individuals, assuming that the impact of activity-induced blood flow changes on conduit arteries, if any, should be seen in these subjects. We examined 21 highly endurance-trained athletes (A), 10 paraplegic subjects (P), and 20 sedentary subjects (S) by means of noninvasive ultrasound. As a result, the CFA diameter and compliance were highest in A (9.7+/-0.81 mm; 1.84 +/-0.54 mm(2)/kPa) and lowest in P (5.9+/-0.7 mm; 0.54+/-0.27 mm(2)/kPa) compared with S (8.3+/-1.0 mm; 0.92+/-0.48 mm(2)/kPa) with P <0.01 among the groups. Both parameters correlated with each other (r = 0.62; P<0.01). Compared with A (378+/-84 s(-1); 37+/-15 s(-1)) and S (356+/-113 s(-1); 36+/-20 s(-1)), the peak and mean shear rates of the CFA were almost or more than doubled in P (588+/-120 s(-1); 89+/-26 s(-1)). In the CCA, only the compliance and peak shear rate showed significant differences among the groups (A: 1.28+/-0.47 mm(2)/kPa, 660+/-138 s(-1); S: 1.04+/-0.27 mm(2)/kPa, 588+/-109 s(-1); P: 0.65+/- 0.22 mm(2)/kPa, 490+/-149 s(-1); P<0.05). In conclusion, the results suggest a structural and functional adaptation in the CFA and a predominantly functional adaptation of the arterial wall properties to differences in the physical activity level and associated exercise-induced blood flow changes in the CCA. The results for humans confirm those from animal experiments. Similar shear rate values of S and P in the CFA support the hypothesis of constant shear stress regulation due to local blood flow changes in humans. On the other hand, the increased shear rate in the CFA in P indicates an at least partially nonphysiological response of the arterial wall in long-term chronic sympathectomy due to a change in local blood flow.     

Effects of biaxial oscillatory shear stress on endothelial cell proliferation and morphology

Wall shear stress (WSS) on anchored cells affects their responses, including cell proliferation and morphology. In this study, the effects of the directionality of pulsatile WSS on endothelial cell proliferation and morphology were investigated for cells grown in a Petri dish orbiting on a shaker platform. Time and location dependent WSS was determined by computational fluid dynamics (CFD). At low orbital speed (50 rpm), WSS was shown to be uniform (0-1 dyne/cm(2)) across the bottom of the dish, while at higher orbital speed (100 and 150 rpm), WSS remained fairly uniform near the center and fluctuated significantly (0-9 dyne/cm(2)) near the side walls of the dish. Since WSS on the bottom of the dish is two-dimensional, a new directional oscillatory shear index (DOSI) was developed to quantify the directionality of oscillating shear. DOSI approached zero for biaxial oscillatory shear of equal magnitudes near the center and approached one for uniaxial pulsatile shear near the wall, where large tangential WSS dominated a much smaller radial component. Near the center (low DOSI), more, smaller and less elongated cells grew, whereas larger cells with greater elongation were observed in the more uniaxial oscillatory shear (high DOSI) near the periphery of the dish. Further, cells aligned with the direction of the largest component of shear but were randomly oriented in low magnitude biaxial shear. Statistical analyses of the individual and interacting effects of multiple factors (DOSI, shear magnitudes and orbital speeds) showed that DOSI significantly affected all the responses, indicating that directionality is an important determinant of cellular responses.     

2型糖尿病患者颈动脉粥样硬化与血尿酸水平的相关性研究

目的：探讨2型糖尿病（T2DM）患者颈动脉粥样硬化与血尿酸水平的相关性。方法：测定214例T2DM患者血清尿酸、血脂、糖化血红蛋白水平及颈动脉中层内膜厚度（IMT）,按颈动脉IMT分为4组：A组：无动脉粥样硬化组;B组：动脉粥样硬化组,C组：斑块形成组,D组：管腔狭窄组。比较各组生化指标,并分析颈动脉粥样硬化与血清尿酸水平的相关性。结果：各组性别、年龄、TC、HDL、LDL无显著差异;C组血清TG水平较A组低（P=0.02）,D组血清HbA1c水平较A组（P=0.038）及B组（P=0.015）显著降低。D组血清尿酸水平与A组相比显著升高（P=0.001）,但D组与B、C组及A组与B、C组间差异均无统计学意义;相关分析显示颈动脉粥样硬化程度与血清尿酸水平呈显著正相关（P=0.002）,相关系数为0.201。结论：高血清尿酸水平可能是导致T2DM患者颈动脉粥样硬化的危险因素之一,需慎重处理T2DM患者高尿酸血症问题。     

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73 Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.