Flow-induced control of arterial lumen

Blood flow velocity is a factor that affects the diameter of arteries. In order to investigate the flow-induced arterial dilatation, the outer diameter of the femoral, common carotid or renal arteries of anaesthetized cats was measured during perfusion of these arteries with blood or plasma-substituting solutions under conditions of stabilized perfusion pressure. It has been shown that, whatever the perfusate, blood or a substituent, an increase in flow makes the artery to dilate. Consequently, the flow-induced dilatation is not due to any blood-borne humoral factor. As an increase in the solution's viscosity causes dilatation even at constant flow-rate and pressure in the artery, the effect is to be ascribed to the ability of the vascular wall to perceive shear stress. As far as removal of endothelium eliminates the dilatation evoked by increasing flow or fluid viscosity, it may be concluded that the flow-induced dilatation is due to the sensitivity to shear stress of the endothelium.     

The effect of carbon dioxide on Doppler flow velocity waveforms in the human fetus.

Twelve healthy pregnant women were studied between 35 to 40 weeks gestation to determine the effect of carbon dioxide on the Doppler flow velocity waveform in the cerebral and umbilical arteries of the human fetus near term. The Resistance index (RI), as an index of vascular resistance, was calculated for the internal carotid and umbilical arteries during a control period while patients breathed room air followed by three randomized 15-30 min study periods with patients breathing either room air, a prepared gas mixture with 2% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The RI of the internal carotid and umbilical arteries both showed a significant inverse relationship to maternal end-tidal PCO2 with a greater negative slope for RI plotted against end-tidal PCO2 in the internal carotid artery (0.0153) than in the umbilical artery (0.0047). The change in the RI as an index of changing vascular resistance, suggests that carbon dioxide is also an important determinant of cerebral blood flow in the human fetus, as previously described for fetal sheep, with a lesser although significant effect on umbilical blood flow.     

Roles of fluid shear stress in physiological regulation of vascular structure and function

The effects of fluid shear stress on the function and structure of the vascular system are outlined, based on the findings obtained in our laboratory or of our colleagues. First, it is pointed out that the adaptive response of the vascular wall to flow changes which we observed in the canine carotid artery shunted with the jugular vein altering the internal diameter to keep the wall shear stress constant, can attain the optimum vascular branching structure as predicted in the minimum work model by Murray. Electronmicroscopic studies of similarly shunted arteries revealing various morphological changes in the endothelial cells have suggested that the shear stress initially affects the endothelium. The in vitro experiments using cultured endothelial cells as well have exhibited that the mitotic activity of the cells significantly increases by applying fluid shear stress. From these findings, it is concluded that the adaptive response of the endothelium to the fluid shear stress is an inherent and key process locally regulating the vascular system to be in the most functional state.     

In vivo demonstration of flow recirculation and turbulence downstream of graded stenoses in canine arteries

The velocity field around arterial stenoses was investigated using a pulsed doppler velocimeter in vivo. Asymmetric zones of recirculation were identified by systolic flow reversal in the post-stenotic field in carotid and iliac arteries of anesthetised dogs. There was a close correlation between shear intensity and turbulence as estimated by the velocity difference between the jet and the recirculation zone and by maximum spectral width respectively. Under the conditions of these experiments, stenosis grade (% diameter reduction) dominated hemodynamic variables such as Reynolds number, oscillation and pulsatility in determining the intensity of turbulence. The method used does not appear to have sufficient resolution to distinguish between turbulence and discrete oscillating velocities (vorticity) nor to allow determination of wall shear stress though the pattern of change of the latter is similar to that found downstream of axisymmetric stenosis in models using steady flow.     

Localization of atherosclerotic lesions in the curving sites of human internal carotid arteries

We studied the distribution of the early atherosclerotic lesions in the curving sites of the human internal carotid arteries composed of the carotid siphon portion (part I) and carotid canal portion (part II). These early atherosclerotic lesions included a localized cloudy thickening with pallor, slight elevation, a non-fibrotic lesion and gray-white or yellowish-white, firm, elevated fibrous plaques. These lesions had the same pattern-distribution in each curving artery. Both were located in the distal regions from the middle of the inner curvature of parts I and II, where eddying fluid motions and directional change in the wall shear stress were considered to occur. In part I, there was a localized cloudy thickening in the younger subjects (average age: 22.8 years) rather than fibrous plaques (average age: 63.3 years). A positive correlation between the extent of the surface areas involved with fibrous plaques and the age of subjects was found in parts I and II. The extent of the surface areas involved with fibrous plaques was significantly greater in part I (26.9%) than in part II (7.85%). The radius of curvature was shorter in the former than in the latter. These results suggest that hemodynamic factors associated with flow in the curving sites of arteries may be important for the localization and progression of atherosclerotic lesions.     

Laser Doppler anemometer measurements of pulsatile flow in a model carotid bifurcation

Hemodynamics at the human carotid bifurcation is important to the understanding of atherosclerotic plaque initiation and progression as well as to the diagnosis of clinically important disease. Laser Doppler anemometry was performed in a large scale model of an average human carotid. Pulsatile waveforms and physiologic flow divisions were incorporated. Disturbance levels and shear stresses were computed from ensemble averages of the velocity waveform measurements. Flow in the common carotid was laminar and symmetric. Flow patterns in the sinus, however, were complex and varied considerably during the cycle. Strong helical patterns and outer wall flow separation waxed and waned during each systole. The changing flow patterns resulted in an oscillatory shear stress at the outer wall ranging from -13 to 9 dyn cm-2 during systole with a time-averaged mean of only -0.5 dyn cm-2. This contrasts markedly with an inner wall shear stress range of 17-50, (mean 26) dyn cm-2. The region of transient separation was confined to the carotid sinus outer wall with no reverse velocities detected in the distal internal carotid. Notable disturbance velocities were also time-dependent, occurring only during the deceleration phase of systole and the beginning of diastole. The present pulsatile flow studies have aided in identifying hemodynamic conditions which correlate with early intimal thickening and predict the physiologic level of flow disturbances in the bulb of undiseased internal carotid arteries.     

Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation.

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.     

Lower wall shear rate of the common carotid artery in treated type 2 diabetes mellitus with metabolic syndrome

Arterial sites with low wall shear stress (WSS) are more prone to the development of atherosclerotic plaques, as was observed in carotid arteries in subjects with atherosclerosis risk factors. Type 2 diabetes mellitus (DM), hypertension, hyperlipidemia and other components of the metabolic syndrome, are associated with high risk for symptomatic cerebrovascular disease. It was shown by others that untreated type 2 DM is associated with lower WSS in common carotid arteries. However, the cardiovascular risk of type 2 DM could be modified by therapy. The aim of our study was to test the hypothesis that treated type 2 DM subjects with metabolic syndrome still have lower WSS in common carotid arteries than healthy controls. We enrolled 26 compensated DM subjects with metabolic syndrome, treated by metformin, statins and ACEI for more than 6 months, and 22 aged-comparable healthy controls. Wall shear rate (WSR) was used as a measure of WSS. A linear 3-11 MHz probe was used to measure blood velocity and internal diameter in the common carotid arteries. We compared observed values of WSR adjusted for age by ANCOVA. Wall shear rate was significantly lower in DM group than in control subjects: peak (systolic) values of wall shear rate were 410+/-130 s(-1) vs. 487+/-111 s(-1) (p<0.005). DM subjects had significantly lower WSR, because of both thinner lumen and slower blood flow velocities. Lower WSR was accompanied by higher IMT (0.73+/-0.12 mm vs. 0.64+/-0.11 mm, p<0.001). Treated subjects with compensated type 2 DM with metabolic syndrome still have atherogenic hemodynamic profile. These findings might help to understand faster progression of atherosclerosis in diabetic subjects with metabolic syndrome despite up-to-date medication.     

Arterial adaptations to altered blood flow

Arterial remodeling in response to altered blood flow is believed to be critical to vascular adaptations to developmental, physiological, pathological, and therapeutically induced changes in blood flow. To assess this remodeling, we used left-to-right carotid anastomosis to increase blood flow in the right common carotid arteries of adult rabbits by 60%. After 2 months, these vessels exhibited no compensatory enlargement. In contrast, the same procedure performed in 5- to 6-week-old weanling rabbits resulted in accelerated growth of the vessels: diameters exceeded those of control arteries by 19% after 2 months. Common carotid arteries in adult rabbits remodeled to produce a diameter reduced by 23% when blood flow was reduced by 63% by external carotid ligation. This adaptation restored shear stress exerted on the vessel wall to control levels. The reduced diameter was not reversed when the vessels were maximally dilated with nitroprusside, adenosine, and forskolin; however, normal diameters were restored within 1 week when normal blood flows were reestablished. Thus, the adult arteries did not respond to increased blood flow produced by the anastomosis, but this procedure did reverse adaptations to decreased flow. In contrast, immature arteries were responsive to this increase in blood flow, even in the absence of prior flow modulation.     

Structural–functional characteristics of brachiocephalic vessels in hypertensive patients under changed atmospheric pressure

The ultrasonic location technique was used to measure the intima-media thickness (IMT) as well as the internal systolic diameter of and the linear blood velocity (LBV) in the cervical arteries in subjects with initial stages of hypertension. Correlation analysis elicited a temporal contingency between these parameters and daily average values of atmospheric pressure. Thus, the common carotid artery IMT tended to increase on high-pressure days. In addition, diameters of the common and internal carotid arteries and vertebral artery were narrowed and, consequently, LBV in these vessels increased. This relationship is more evident in men than women and in elderly subjects than young. These results are suggestive of a vasoconstrictive effect of high atmospheric pressure on these arteries. The relationship is not universal, as it is nonlinear for the diameter of the internal carotid artery and inverse for the external one. This implies different sensitivity of arteries to the factor under study and possible blood redistribution in the arterial tree depending on external pressure. The relationship was observed equally on the day of investigation and previous days, which points to its temporal stability.     

颈动脉血管壁切应力的分析

动脉中管壁的脉动低切应力在动脉粥样硬化形成中起始动和主要的决定作用。本文比较了几种计算血管壁切应力的方法,认为采用有约束的弹性管模型计算获得的动脉壁切应力更适合于临床应用。根据检测得到的正常人和动脉硬化性脑血管病患者的颈动脉血流速度、血管管径等数据,计算两者的颈动脉壁面切应力。研究发现动脉硬化性脑血管病患者的壁面切应力比正常人显著减小。这表明,颈动脉的壁面切应力可以作为动脉硬化性脑血管疾病的早期诊断的重要参考指标。     

A two-dimensional numerical analysis of unsteady flow in the carotid artery bifurcation. A comparison with three-dimensional in-vitro measurements and the influence of minor stenoses

In the present study a two-dimensional finite element model for incompressible Newtonian flow is applicated to the modelling of carotid artery flow. In earlier studies, the numerical model was validated experimentally for several flow configurations. In general the pulsatile flow is characterized by reversed flow regions at the non-divider side walls of both the internal and external carotid arteries. The unsteadiness of the flow is associated with rather complex spatial and temporal velocity distributions and leads to temporal variations of the location and length of the reversed flow regions. As a consequence, pronounced spatial and temporal variations in the wall shear stresses are found. At the non-divider side walls, wall shear stresses are relatively low and exhibits an oscillatory behaviour in space and time. At the divider side walls, wall shear stresses are relatively high and approximately follow the flow rate distribution in time. The aim of this study is not only to present two-dimensional calculations but also to compare the calculated two-dimensional velocity profiles with those from three-dimensional experiments. It is observed that in the common carotid artery and in the proximal parts of the internal and external carotid arteries, the two-dimensional numerical model provides valuable information with respect to the three-dimensional configuration. In the more distal parts of especially the internal carotid artery, deviations are found between the two-dimensional numerical and three-dimensional experimental model. These deviations can mainly be attributed to the neglect of the secondary velocity distribution in the two-dimensional model. In the two-dimensional numerical model the influence of a minor stenosis in the internal carotid artery is hardly distinguishable from a minor geometrical variation without stenosis. Full three-dimensional analyses of the influence of minor stenoses are needed to prove numerically whether in-vivo measurements of the axial velocity distribution are useful in the detection of minor stenoses.     

Velocity measurements in steady flow through axisymmetric stenoses at moderate Reynolds numbers

The velocity field in the neighborhood of axisymmetric constrictions in rigid tubes was investigated using laser Doppler anemometry and flow visualization. Upstream flow conditions were steady; and Reynolds numbers were in the range 500-2000, values which are representative of the larger arteries in humans. Stenoses of 25, 50 and 75% area reduction were studied. Velocity profiles are presented in sufficient detail to allow comparison with computational biofluid dynamics models. Wall shear stresses were estimated from the near wall velocity gradient, and the nature of observed poststenotic flow disturbances is discussed. Results indicate that flow disturbances of discrete oscillation frequency may be more valuable than turbulence as an indicator of early stages of stenosis development. Additionally, despite the fact that poststenotic turbulence exists for the higher degrees of stenosis and Reynolds numbers, the resulting wall shear stresses are only three to four times greater than the Poiseuille value and are considerably less than the wall shear stress within the stenosis itself.     

低切应力作用下体外培养动脉内皮细胞内皮素的表达

研究了切应力对完整血管的生物学作用以及应力引起血管重建过程中内皮素(ET)的变化．采用血管体外应力培养系统,将一段完整的猪颈总动脉在体外进行培养,设切应力分别为2Pa(％组)和0．5Pa(S5组),设置2、4、6．8．10．12、14．16和18h共9个时相观察点,非平衡法放射免疫检测灌流液中的ET含量．通过Logistic曲线方程拟合,分析切应力作用下完整动脉ET表达变化规律。结果显示：S20组ET总体变化不明显;S5组分泌速率在前12．37h内明显上升,而后又逐渐下降趋于稳定,且始终高于S20组。说明低切应力作用下ET的表达及分泌增高．结果提示,在低切应力引起的血管重建中,ET可能起着重要作用。     

Blood flow and vessel mechanics in a physiologically realistic model of a human carotid arterial bifurcation

The pulsatile flow in an anatomically realistic compliant human carotid bifurcation was simulated numerically. Pressure and mass flow waveforms in the carotid arteries were obtained from an individual subject using non-invasive techniques. The geometry of the computational model was reconstructed from magnetic resonance angiograms. Maps of time-average wall shear stress, contours of velocity in the flow field as well as wall movement and tensile stress on the arterial wall are all presented. Inconsistent with previous findings from idealised geometry models, flow in the carotid sinus is dominated by a strong helical flow accompanied by a single secondary vortex motion. This type of flow is induced primarily by the asymmetry and curvature of the in vivo geometry. Flow simulations have been carried out under the rigid wall assumption and for the compliant wall, respectively. Comparison of the results demonstrates the quantitative influence of the vessel wall motion. Generally there is a reduction in the magnitude of wall shear stress, with its degree depending on location and phase of the cardiac cycle. The region of slow or reversed flow was greater, in both spatial and temporal terms in the compliant model, but the global characteristics of the flow and stress patterns remain unchanged. The analysis of mechanical stresses on the vessel surface shows a complicated stress field. Stress concentration occurs at both the anterior and posterior aspects of the proximal internal bulb. These are also regions of low wall shear stress. The comparison of computed and measured wall movement generally shows good agreement.     

Longitudinal movements and resulting shear strain of the arterial wall

There has been little interest in the longitudinal movement of the arterial wall. It has been assumed that this movement is negligible compared with the diameter change. Using a new high-resolution noninvasive ultrasonic method, we measured longitudinal movements and diameter change of the common carotid artery of 10 healthy humans. During the cardiac cycle, a distinct bidirectional longitudinal movement of the intima-media complex could be observed in all the subjects. An antegrade longitudinal movement, i.e., in the direction of blood flow, in early systole [0.39 mm (SD 0.26)] was followed by a retrograde longitudinal movement, i.e., in the direction opposite blood flow [-0.52 mm (SD 0.27)], later in systole and a second antegrade longitudinal movement [0.41 mm (SD 0.33)] in diastole. The corresponding diameter change was 0.65 mm (SD 0.19). The adventitial region showed the same basic pattern of longitudinal movement; however, the magnitude of the movements was smaller than that of the intima-media complex, thereby introducing shear strain and, thus, shear stress within the wall [maximum shear strain between the intima-media complex and the adventitial region was 0.36 rad (SD 0.26). These phenomena have not previously been described. Measurements were also performed on the abdominal aorta (n = 3) and brachial (n = 3) and popliteal (n = 3) arteries. Our new information seems to be of fundamental importance for further study and evaluation of vascular biology and hemodynamics and, thus, for study of atherosclerosis and vascular diseases.     

A numerical and experimental analysis of the flow field in a two-dimensional model of the human carotid artery bifurcation

Axial velocities were measured in an enlarged, two-dimensional, rigid model of the carotid artery bifurcation by means of a laser-Doppler anemometer, under both steady and unsteady flow conditions. Also a numerical model was developed, based on the finite element approximation of the Navier-Stokes and continuity equations. From this study it appeared that the numerically predicted velocities agree well with the experimentally obtained values. Besides, the bifurcation hardly influenced the upstream flow in the main branch (common carotid artery), high velocity gradients were observed at the divider walls of the daughter branches (internal and external carotid arteries) and large zones with reversed flow were present near the nondivider walls of these branches. For steady flow the maximal diameter of this zone at the entrance of the internal carotid artery (carotid sinus) was about 25% of the local diameter of this branch. For unsteady flow this zone was absent during the initial phase of flow acceleration and maximal at the end of flow deceleration with a maximal diameter of about 50% of the local diameter of the carotid sinus.     

Characterization of the in vivo wall shear stress environment of human fetus umbilical arteries and veins

The endothelial cells of the umbilical vessels are frequently used in mechanobiology experiments. They are known to respond to wall shear stress (WSS) of blood flow, which influences vascular growth and remodeling. The in vivo environment of umbilical vascular WSS, however, is not well characterized. In this study, we performed detailed characterization of the umbilical vascular WSS environments using clinical ultrasound scans combined with computational simulations. Doppler ultrasound scans of 28 normal human fetuses from 32nd to 33rd gestational weeks were investigated. Vascular cross-sectional areas were quantified through 3D reconstruction of the vascular geometry from 3D B-mode ultrasound images, and flow velocities were quantified through pulse wave Doppler. WSS in umbilical vein was computed with Poiseuille’s equation, whereas WSS in umbilical artery was obtained via computational fluid dynamics simulations of the helical arterial geometry. Results showed that blood flow velocity for umbilical artery and vein did not correlate with vascular sizes, suggesting that velocity had a very weak trend with or remained constant over vascular sizes. Average WSS for umbilical arteries and vein was 2.81 and 0.52 Pa, respectively. Umbilical vein WSS showed a significant negative correlation with the vessel diameter, but umbilical artery did not show any correlation. We hypothesize that this may be due to differential regulation of vascular sizes based on WSS sensing. Due to the helical geometry of umbilical arteries, bending of the umbilical cord did not significantly alter the vascular resistance or WSS, unlike that in the umbilical veins. We hypothesize that the helical shape of umbilical arteries may be an adaptation feature to render a higher constancy of WSS and flow in the arteries despite umbilical cord bending.     

Pulsatile non-Newtonian flow characteristics in a three-dimensional human carotid bifurcation model.

Numerical analysis of flow phenomena and wall shear stresses in the human carotid artery bifurcation has been carried out using a three-dimensional geometrical model. The primary aim of this study is the detailed discussion of non-Newtonian flow velocity and wall shear stress during the pulse cycle. A comparison of non-Newtonian and Newtonian results is also presented. The applied non-Newtonian behavior of blood is based on measured dynamic viscosity. In the foreground of discussion are the flow characteristics in the carotid sinus. The investigation shows complex flow patterns especially in the carotid sinus where flow separation occurs at the outer wall throughout the systolic deceleration phase. The changing sign of the velocity near the outer sinus wall results in oscillating shear stress during the pulse cycle. At the outer wall of the sinus at maximum diameter level the shear stress ranges from -1.92 N/m2 to 1.22 N/m2 with a time-averaged value of 0.04 N/m2. At the inner wall of the sinus at maximum diameter level the shear stress range is from 1.16 N/m2 to 4.18 N/m2 with a mean of 1.97 N/m2. The comparison of non-Newtonian and Newtonian results indicates unchanged flow phenomena and rather minor differences in the basic flow characteristics.     

MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models

Pulsatile flow was studied in physiologically realistic models of a normal and a moderately stenosed (30% diameter reduction) human carotid bifurcation. Time-resolved velocity measurements were made using magnetic resonance imaging, from which wall shear stress (WSS) vectors were calculated. Velocity measurements in the inflow and outflow regions were also used as boundary conditions for a computational fluid dynamics (CFD) model. Experimental flow patterns and derived WSS vectors were compared qualitatively with the corresponding CFD predictions. In the stenosed phantom, flow in the bulb region of the "internal carotid artery" was concentrated along the outer wall, with a region of low and recirculating flow near the inner wall. In the normal phantom, the converse was found, with a low flow region near the outer wall of the bulb. Time-averaged WSS and oscillatory shear index were also markedly different for the two phantoms.