Differential structural adaptation to haemodynamics along single rat cremaster arterioles

We tested the hypothesis that under physiological conditions, arterioles match their diameter to the level of shear stress. Haemodynamic and anatomical data were obtained in segments of the first-order arteriole of the rat cremaster muscle. Along this segment of ∼10 mm in length, local blood pressure decreased from 68 ± 4 mmHg upstream to 54 ± 3 mmHg downstream ( n = 5). Pulse pressure decreased from 8.2 ± 1.3 mmHg upstream to 4.1 ± 0.6 mmHg downstream. At the same locations, an increase in arteriolar diameter was measured in vivo, from 179 ± 4 μm upstream to 203 ± 4 μm downstream ( n = 10). In vitro pressure-diameter relations of maximally dilated vessels showed that the passive diameter was larger in downstream than upstream segments over a 15–125 mmHg pressure range ( n = 18). The wall stress was similar for the upstream vs. downstream location: 266 ± 16 vs. 260 ± 14 mN mm⁻². However, shear stress decreased from 30 ± 5 to 21 ± 5 dyn cm⁻² (3.0 ± 0.5 to 2.1 ± 0.5 N m⁻²; n = 4) along the artery. In conclusion, these results demonstrate that shear stress is not the only factor in determining vascular calibre. We suggest that arteriolar calibre may rather depend on an interplay between shear stress and the local pressure profile.     

管径比对全阻塞动脉旁路移植流场影响的数值研究

目的 研究管径比对全阻塞动脉旁路移植流场的影响,为指导动脉旁路移植手术,减少术后再狭窄提供理论依据。方法 采用数值方法研究5种不同移植管与主血管的管径比对全阻塞情况下动脉旁路移植流场的影响,分析速度、二次流、壁面切应力和壁面切应力梯度等血流动力学参数的分布及其随管径比增大的改变。同时,为表明本文所采用模型的合理性,针对目前常使用的两类模型,比较在管径比1.0情况下全阻塞完整模型（Model A）、全阻塞局部模型（Model B）和75％狭窄完整模型（Model C）之间的血流动力学差异。结果 Model A和Model C的血流动力学特性是完全不同的;移植管顶部截面内的速度分布对下游吻合处的主血管底部壁面切应力的影响是显著的,最大相差达79％。大管径比时,主血管底部的壁面低切应力区较大,但壁面切应力分布均匀,壁面切应力梯度较小。而小管径比时,主血管底部的壁面低切应力区较小,但壁面切应力梯度较大。结论 采用整体模型单独研究全阻塞情况下的管径比对流场的影响是有必要的。管径比对全阻塞动脉旁路移植的流场具有显著影响,采用大管径比进行动脉旁路移植将有助于缓解吻合口处由于再狭窄而产生的阻塞。     

Numerical simulations of unsteady flows in a stenosed coronary bypass graft

Using the finite element method, physiological blood flows through a three-dimensional model of a coronary graft are numerically analysed. The model includes a stenosis shape in the host artery upstream from the anastomosis. Recirculating areas, secondary flows, wall shear stress (WSS) and spatial wall shear stress gradients (WSSGs) are studied for different flow repartitions and at different times in the cycle. The temporal and spatial evolutions of the recirculating areas downstream from the stenosis, their interactions with the flow issued from the graft and their associated WSSs highlight that the presence of the stenosis in the recipient artery is essential for prediction of the evolution of a grafting at the beginning of its implantation. The areas downstream from the stenosis expansion, non-existent for a host artery without stenosis, are submitted to low and oscillating WSS between −0.5 and 0 Nm⁻². The stagnation point on the recipient artery floor is subjected to high positive and negative WSSG_nd values, and its location is dependent on the residual flow through the stenosis.     

Differential inhibition by hyperglycaemia of shear stress- but not acetylcholine-mediated dilatation in the iliac artery of the anaesthetized pig

Clinical hyperglycaemia affects vascular endothelial function, but the effect on shear stress-induced arterial dilatation has not yet been established. We hypothesized that hyperglycaemia would inhibit this response via impaired glycocalyx mechanotransduction. Experiments were carried out in the anaesthetized pig in which pressure, blood flow and diameter of the left iliac artery were measured at two sites: proximal ( d1 ) and distal ( d2 ). Infusion of glucose, sufficient to raise blood glucose to 16–30 m m along the whole length of the artery, attenuated the shear stress-dependent dilatation in both sections of the artery with preservation of the responses to acetylcholine. The distal site was then isolated using snares and the lumen exposed to blood containing 25–35 m m glucose for 20 min. In the control situation, after exposure of both sections to normoglycaemia (5.7 m m glucose), both sections of artery showed increases in diameter in response to shear stress and acetylcholine. Hyperglycaemia attenuated the shear stress-dependent dilatation in the distal section only ( P < 0.25), but not the response to acetylcholine. It is concluded from these results that the hyperglycaemia-impaired dilatation is consistent with loss of mechanotransducing properties of the endothelial glycocalyx by hyperglycaemia. These findings offer a possible explanation for the increased incidence of vascular disease in diabetic patients.     

弹性动脉狭窄血管内血液流动的ALE方法分析

针对弹性动脉狭窄血管中血液的流动状况,采用任意拉格朗日-欧拉方法(ALE),在给定相同的边界条件下模拟出了弹性血管和刚性血管中血流速度和压力的变化情况,分析了不同狭窄程度模型的血流状态.结果表明:随着动脉的狭窄程度增加,其中心流速越来越大,窄前压力逐渐升高,窄后压力逐渐降低,狭窄前后的压差单调增加;刚性血管无法对人体正常生理状态进行比较好的模拟,其计算所得结论与实际情况差距较大.说明ALE方法对血液流动的数值研究是可行的.     

Morphological features of blood access stenosis and results of noninvasive angioplasty

We investigated a connection between the results of noninvasive angioplasty for the blood access stenosis and its morphological features in 37 dialysis cases. In 3 cases presenting stenosis in the original artery, the area could not be dilated by noninvasive techniques. In 4 cases with stenosis in the arterialized vein downstream of the needle insertion points for extracorporeal circulation, 3 showed long-term dilatation by the procedures. In 30 cases having stenosis upstream of the points, 16 showed long-term dilatation. In the unsuccessful cases, the angle formed between the axes of the stenosed portion and the normal vessel was over 39 degrees, and the distance between the anastomosis and the stenosed portion was less than 11 mm.     

Characteristics of the response of the iliac artery to wall shear stress in the anaesthetized pig

The functional significance of shear stress-induced vasodilatation in large conduit arteries is unclear since changes in the diameter have little effect on the resistance to blood flow. However, changes in diameter have a relatively large effect on wall shear stress which suggests that the function of flow-mediated dilatation is to reduce wall shear stress. The mean and pulsatile components of shear stress vary widely throughout the arterial system and areas of low mean and high amplitude of wall shear stress are prone to the development of atheroma. In this study, using an in vivo model with the ability to control flow rate and amplitude of flow independently, we investigated the characteristics of the response of the iliac artery to variations in both the mean and amplitude of wall shear stress. The results of this study confirm that increases in mean wall shear stress are an important stimulus for the release of nitric oxide by the endothelium as indicated by changes in arterial diameter and show for the first time, in vivo , that increases in the amplitude of the pulsatile component of shear stress have a small but significant inhibitory effect on this response. A negative feedback mechanism was identified whereby increases in shear stress brought about by increases in blood flow are reduced by the release of nitric oxide from the endothelium causing dilatation of the artery, thus decreasing the stimulus to cell adhesion and, through a direct action of nitric oxide, inhibiting the process of cell adhesion. The results also provide an explanation for the uneven distribution of atheroma throughout the arterial system, which is related to the ratio of pulsatile to mean shear stress and consequent variability in the production of NO.     

Coronary artery remodelling and the assessment of stenosis by pathologists

When atherosclerotic plaques develop, the cross- sectional area of the artery at that point often increases to accommodate the plaque without any reduction in lumen size. In consequence the angiogram does not detect a high proportion of atherosclerotic plaques. The increase in size of the artery (compensatory dilatation − arterial remodelling) varies widely in degree between different plaques even in the same artery. Dilatation of a degree to prevent any loss of lumen size is regarded as adequate compensatory dilatation. In contrast, other plaques are associated with no or minimal increase in the vessel cross-sectional area and a reduction in lumen size is present (inadequate compensation). High-grade stenosis is in particular associated with a total failure of remodelling. Such plaques may have had a rapid growth phase, out-pacing the ability of the medial smooth muscle cells to undergo a rearrangement.
The phenomenon of remodelling has important consequences for pathologists who use the traditional method of comparing the lumen size relative to the cross-sectional area of the vessel at the site of a plaque to measure stenosis. The area of the vessel at this point may be anything up to 60% above its size before the plaque developed. An error is introduced which on average overestimates diameter stenosis by 30% when compared to an angiographic equivalent method in which the lumen size at the lesion is compared to the lumen size at an adjacent segment of artery without a plaque.     

The influences of stenosis on the downstream flow pattern in curved arteries

The influence of stenosis on the pulsatile blood flow pattern in curved arteries with stenosis at inner wall was investigated by computer simulations. Numerical calculations were performed with various values of physiological parameters to examine the effect of a stenosis on the hemodynamic characteristics such as secondary flow, flow separation, wall shear stress (WSS) and pressure drop. The results demonstrated that when the severity of a stenosis at the inner wall of a curved artery reaches a certain level, the flow pattern in the downstream of the artery shows a dramatic change compared to that of a curved artery with no stenosis. According to previous studies, a flow separation occurs at the inner wall of the bend in a curved artery. The present work reports an analysis of such a flow separation area at the inner wall of the post stenosis region in curved arteries with a stenosis. In addition, another area of flow separation with low and oscillating WSS and blood pressure at the outer wall in a downstream tube was also found and investigated. The observed characteristic change of the flow downstream may suggest a formation of a new plaque at the outer wall downstream.     

Hemodynamics Simulation of Stenosed Coronary Bypass Graft

By means of FEM, the physiological blood flow in coronary bypass graft is simulated. The stenosis in coronary artery is involved in the graft model,and the deformation of graft end to allow the surgical suture with a smaller diameter coronary is taken into consideration. The flow pattern, secondary flow and wall shear stress in the vicinity of anastomosis are analyzed. It is shown that a zone of low wall stress and high wall stress gradient exists downstream the toe. The floor opposed to the anastomosis is an area of high wall stress and high wall stress gradient. Both the toe downstream and the anastomosis bottom floor are prone to intimal hyperplasia.     

冠状动脉造影和三磷酸腺苷负荷超声心动图对川崎病冠状动脉损害远期追踪的价值

目的探讨选择性冠状动脉造影及三磷酸腺苷负荷超声心动图对川崎病（KD）冠状动脉损害远期追踪的价值。方法选取1999至2007年广州市儿童医院KD急性期超声心动图检查发现合并冠状动脉损害的患儿,同时采用三磷酸腺苷负荷超声心动图及选择性冠状动脉造影于恢复期进行远期随访。结果依据纳入标准和排除标准逐层筛选,确定9例KD患儿为本研究的样本。男8例,女1例,急性期发病年龄为1-10岁,平均（4.44±3.09）岁。检查时年龄4-12岁,平均（7.89±2.62）岁。追踪时间1.5~7年,平均（3.44±1.67）年。急性期超声心动图示9例患儿中冠状动脉巨瘤5例,冠状动脉瘤3例,冠状动脉扩张1例。三磷酸腺苷负荷超声心动图示：节段性室壁运动异常6/9例;冠状动脉血流储备下降5/9例。冠状动脉造影示：双侧主干冠状动脉瘤4例,同时伴远端动脉瘤3处,冠状动脉左前降支狭窄1处,并冠状动脉扭曲,狭窄或充盈缺损3处,附近侧支血管形成1处;左前降支动脉瘤、右冠状动脉闭塞伴侧支循环形成1例,冠状动脉扩张4例。与同期超声心动图检查比较,冠状动脉造影新发现冠状动脉远端瘤3处,右冠状动脉远端狭窄2处,左前降支狭窄1处,右冠状动脉闭塞伴侧支血管形成1例。5例三磷酸腺苷负荷超声心动图检查结果阳性者与冠状动脉造影比较：均发现相应冠状动脉支狭窄或充盈缺损表现;1例三磷酸腺苷负荷超声心动图检查结果阳性,冠状动脉造影仅见轻度冠状动脉扩张。结论KD合并冠状动脉损害特别是动脉瘤造成的心脏损害可长期存在。对于远期追踪观察KD患儿冠状动脉病变,三磷酸腺苷负荷超声心动图具无创、安全可靠的优点,是判断心肌缺血的重要方法;选择性冠状动脉造影可明确显示冠状动脉病变的位置、形态、数目及严重程度,特别对冠状动脉狭窄、闭塞及远端病变能做出准确的评估。两种方?     

冠状动脉移植管的血流动力学数值模拟

采用有限元数值计算的方法，模拟了冠状动脉搭桥术中移植管内的生理流动。计算模型包括了冠状动脉狭窄，并考虑了由于移植管直径大于冠状动脉直径而在两者缝合时移植管的变形。计算结果分析了缝合区附近的流场、二次流、壁面切应力在心动周期内的时空分布情况。计算结果表明，在缝合前端下游，存在一个低切应力、高切应力梯度的区域，在缝合区底部存在一个高切应力、高切应力梯度的区域。这两个区域都是内皮细胞增生并造成移植管术后再阻塞的危险部位。     

Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium‐dependent vasodilation in the femoral artery of developing piglets

Mechanisms mediating endothelium‐dependent vasodilation were investigated in femoral artery rings from <2‐day‐old (newborn) and 2‐week‐old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)‐cyclic 3′,5′‐guanosine monophosphate (cGMP) and K⁺ channel‐activation to acetylcholine (ACh)‐induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K⁺ channel blockade and the intra‐arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS‐inhibitors N ^G‐monomethyl‐L ‐arginine acetate (L ‐NMMA; 100 μM ) or N^G‐nitro‐L ‐arginine (L ‐NOARG; 1–100 μM ), however, relaxation was significantly more reduced in femoral artery rings from 2‐week‐old than from newborn, with lower pD₂ values in the older age group. Inhibition of large (BK_Ca) conductance calcium‐sensitive K⁺ channels with tetraethylammonium chloride (TEA; 1 mM ), gave a significant rightward shift in the concentration‐response curves to ACh which was of the same magnitude in both age groups. The ACh‐induced vasodilation was abolished in both age groups by high K⁺ (20 mM ) in combination with L ‐NOARG (100 μM ). The relative increase in cGMP levels after addition of ACh (10 nM ) was significantly larger in rings from newborn compared with 2‐week‐old piglets (12‐ vs. four‐fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K⁺ channel blockade with TEA was the same in femoral artery rings from newborn to 2‐week‐old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.     

Monocyte adhesion and changes in endothelial cell number, morphology, and F-actin distribution elicited by low shear stress in vivo.

Left common carotid arteries of New Zealand white rabbits were ligated rostral to origin of the thyroid artery to reduce flow in the carotid upstream of this branch, and the vessels were examined 5 days later. Estimates of mean shear stress in the upstream carotid artery indicated a decrease of 73% (from 12.1 +/- 1.6 dynes/cm2 to 3.26 +/- 0.58 dynes/cm2). The contralateral common carotid artery carried collateral flow and experienced a 170% increase in shear stress (from 11.3 +/- 1.6 dynes/cm2 to 30.5 +/- 4.6 dynes/cm2). There was an adaptive reduction in the diameter in the left common carotid artery (low shear) from 2.07 +/- 0.06 mm to 1.75 +/- 0.12 mm, but the diameter of the right carotid was unchanged. Fluorescence microscopy and scanning electron microscopy of endothelium exposed to low shear revealed attachment of leukocytes (5.02 +/- 1.59 cells/mm2, mean +/- SE) that were identified as monocytes using the monoclonal antibody HAM 56. Laser confocal microscopy demonstrated that they were migrating across the endothelial cell monolayer. Fluorescence microscopy and scanning electron microscopy of left common carotid artery (low shear) also revealed cell morphology suggestive of endothelial cell desquamation. Endothelial cell loss was confirmed by morphometric determination of cell number (1.29 +/- 0.13 x 10(4) cells/mm length in experimental animals versus 1.71 +/- 0.08 x 10(4) cells/mm length in sham-operated animals). This endothelial cell loss may be an adaptation to a narrowing of carotid arteries exposed to low shear, which reduces luminal surface area of the vessel. Staining of F-actin with rhodamine phalloidin showed that endothelial cells exposed to low shear were less elongated and had fewer stress fibers than normal cells. By contrast, increasing shear stress by two- to threefold caused an increase in the number of stress fibers and a reduction in peripheral actin staining. Distal carotid ligation provided a consistent and well-defined in vivo technique for manipulating shear stresses imposed on a large population of endothelial cells.     

椎动脉狭窄临床病例介入治疗前后椎基底动脉血流状况分析

目的:基于血液和弹性血管壁相互作用的流固耦合方法,探究1例椎动脉颅内段狭窄的临床病例支架植入前后椎基底动脉的血流动力学特性。方法:应用医学建模软件对二维CT数据进行三维重建,得到支架植入前后的椎基底动脉血管模型,采用流固耦合方法对支架植入前后的椎基底动脉血流特性进行数值模拟,分析椎基底动脉的血流动力学特性。结果:支架植入前后椎基底动脉的血液流场、血液压力、血管壁面切应力以及管壁形变量有显著的变化。在支架植入后,基底动脉中间部位两侧受力变得均匀,椎基底动脉内血流速度明显增大,支架植入处压力增大,支架上游压力和支架处切应力减小。结论:在介入治疗后,椎基底动脉内的血流环境及受力情况得到明显改善,当椎动脉发生狭窄后应及时干预治疗,避免累及基底动脉和后循环系统。     

Enhancement of Stent-Induced Thromboembolism by Residual Stenoses: Contribution of Hemodynamics

In vitro stent-induced thromboembolism was altered by the presence of residual stenoses placed upstream or placed upstream and downstream of the stent. Heparinized (3 /ml) bovine blood was gravity fed through a conduit with a deployed coronary stent. Embolism was continuously monitored using a light-scattering microemboli detector, and the thrombus accumulated on the stent at the conclusion of the experiment was assessed gravimetrically. Gaussian stenoses (75% reduction in the cross-sectional area) were placed upstream or upstream and downstream of the stent to alter flow characteristics in the stent region. The presence of stenoses enhanced embolization from the stent in all cases, while end-point thrombus accumulation on the stent decreased with only an upstream stenosis present, and increased when upstream and downstream stenoses were present. Computational fluid dynamics with and without hypothetical model thrombi were used to ascertain the alterations in the flow environment caused by the stenoses and thrombi. Combining the computed hemodynamic parameters with experimental results indicated that increased radial transport of blood components and low wall shear stress provided by the stenoses and thrombi may explain the enhancement of end-point thrombus accumulation. Analysis further showed that thrombi growing at the stenosis-induced reattachment and separation points will be subjected to high shear forces which may explain the increased embolism when stenoses are present. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8719Xx, 8780-y     

Reverse arterial wall shear stress causes nitric oxide-dependent vasodilatation in the anaesthetised dog

The effects of a maintained increase in mean arterial wall shear stress (SS(m)) caused by blood flow in the normal and reverse direction on dilatation of the iliac artery were examined in the anaesthetised dog. Blood flow in the left iliac artery was varied in both the forwards and reverse directions by a perfusion pump connecting the right and left femoral arteries. An increase in blood flow, and therefore SS(m) in either direction, caused an increase in arterial diameter. However, an increase in forwards SS(m) (control 4.1+/-0.11 mm) caused a significantly greater change in arterial diameter than an equivalent increase in the reverse direction (control 4.3+/-0.08), 0.198+/-0.02 mm vs. 0.132+/-0.02 mm (mean+/-SEM) respectively, for the same increase in SS(m) (3.23 N/m(2)). The increase in arterial diameter in response to an increase in forwards or reverse SS(m) was attenuated by L-NAME (80 mg/kg i.v.), indicating that the arterial dilatation was mediated by nitric oxide (NO). These findings confirm that endothelial NO release is dependent on the steady-state SS(m) and that the response occurs irrespective of the direction in which this force is applied, but is attenuated in the reverse direction.     

The effect of arterial wall shear stress on the incremental elasticity of a conduit artery

Aims: The purpose of this investigation was to determine the effects of flow mediated dilatation on arterial incremental elasticity (E_inc). Methods: In four female anaesthetized pigs, the iliac artery and vein were connected by a shunt with a variable resistance which allowed blood flow and therefore shear stress to be regulated. E_inc was calculated from simultaneous records of diameter and pressure throughout a minimum of four cardiac cycles. Results: Passive increases in diameter (～1–2%) throughout a cardiac cycle, brought about by pressure, resulted in a two‐ to threefold increase in E_inc. In contrast, increases in shear stress caused active smooth muscle relaxation and a significant increase in diameter from 3.663 ± 0.215 mm to 4.488 ± 0.163 mm (mean ± SEM, P < 0.05) equivalent to a fractional increase in diameter (fD) of 1.5 with no significant change in mean arterial pressure, 108 ± 2 mmHg to 106 ± 1 mmHg (mean ± SEM). The average value of E_inc per cardiac cycle at baseline was 2.17 ± 0.10 × 10³ kPa and remained relatively constant until fD exceeded 1.3 thereafter increasing to a maximum of 9.23 ± 1.0 × 10³ kPa. Conclusion: These results show that in a conduit artery during the dilatory response to shear stress, the interaction between smooth muscle and collagen operates so as to maintain E_inc relatively constant over much of the working range of dilatation. This is consistent with a model of the arterial wall in which collagen is recruited both by passive stretch, in response to an increase in pressure and therefore wall stress, and also by active contraction of smooth muscle.     

Brachial artery vasodilatation during prolonged lower limb exercise: role of shear rate

We recently observed a marked increase in brachial artery (BA) diameter during prolonged leg cycling exercise. The purpose of the present study was to test the hypothesis that this increase in BA diameter during lower limb exercise is shear stress mediated. Accordingly, we determined whether recapitulation of cycling-induced BA shear rate with forearm heating, a known stimulus evoking shear-induced conduit artery dilatation, would elicit comparable profiles and magnitudes of BA vasodilatation to those observed during cycling. In 12 healthy men, BA diameter and blood velocity were measured simultaneously using Doppler ultrasonography at baseline and every 5 min during 60 min of either steady-state semi-recumbent leg cycling (120 W) or forearm heating. At the onset of cycling, the BA diameter was reduced (-3.9 ± 1.2% at 5 min; P < 0.05), but it subsequently increased throughout the remainder of the exercise bout (+15.1 ± 1.6% at 60 min; P < 0.05). The increase in BA diameter during exercise was accompanied by an approximately 2.5-fold rise in BA mean shear rate (P < 0.05). Similar increases in BA mean shear with forearm heating elicited an equivalent magnitude of BA vasodilatation to that observed during cycling (P > 0.05). Herein, we found that in the absence of exercise the extent of the BA vasodilator response was reproduced when the BA was exposed to comparable magnitudes of shear rate via forearm heating. These results are consistent with the hypothesis that shear stress plays a key role in signalling brachial artery vasodilatation during dynamic leg exercise.     

Simultaneous electrical and mechanical recording in small isolated perfused arteries

A new method is described for simultaneous measurements of electrical and mechanical activity in an intact segment of a small artery (outside diameter 0·3–0·5 mm). A 7–9 mm segment of rabbit middle-cerebral artery was ligated on a Teflon tube connected to a perfusion circuit. The presence of a plug in the tube, flanked by two orifices, forced the physiological solution to flow in the annular space between the tube and the artery wall. Physiological pressures could thus be attained at low rates of flow, and the pressure, measured upstream, was significantly modifed by the slightest constriction or dilatation of the vascular segment. Electrical recording with glass microelectrodes was performed on a short immobilised portion of the artery. The artery and tube were bathed in a physiological solution at 38°C, but perfusing and incubating solutions did not mix. Spontaneous electrical and mechanical activity of middle cerebral arteries is described, together with modifications induced by vasoactive agents.