Influence of stenosis morphology on flow through severely stenotic vessels: implications for plaque rupture

Flow patterns and flow-related stresses contribute to the characterization of health risks, particularly the risk of plaque rupture, posed by a particular atherosclerotic stenosis. Blood flow in the presence of significant plaque deposits is investigated, and the influence of factors such as stenosis morphology and surface irregularity is evaluated. Solutions for three-dimensional, unsteady flow in these stenotic vessels are obtained for an incompressible, Newtonian fluid. The equations of motion are solved numerically using a finite volume formulation. The resulting flow patterns and shear and normal stresses are interpreted with respect to diagnostic implications, including the possibility of plaque rupture. The inadequacy of "percent stenosis" to characterize the risks posed by a particular plaque is demonstrated. Surface irregularity, stenosis aspect ratio, and the shape of the pulsatile waveform all have considerable influence on the flow field and on the stresses on the plaque. A measure of surface irregularity or plaque symmetry, in particular, may complement percent stenosis in diagnosing the risk of plaque rupture.     

An introduction to biofluid mechanics--basic models and applications

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics play a critical role in the development of atherosclerosis and the processes of aging, as well as many other disease processes. Biofluid mechanics play a major role in the cardiovascular system and it is important to understand the forces and movement of blood cells and whole blood as well as the interaction between blood cells and the vessel wall. Fundamental fluid mechanical, which are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects are presented. Measurement techniques for model studies such as LDA, ultrasound, and MRI studies will be discussed. Viscosity and flow behavior changes specifically the creation of vortices and flow disturbances can be used to show how medication can influence flow behavior. Experiments have shown that hemodynamics may have a strong influence on the creation of aneurysms and varicose veins. Other factors such as vessel wall structure are also important. In preliminary studies, it has been demonstrated that geometry and elasticity of vessel walls help determine flow behavior. High velocity fluctuations indicate flow disturbances that should be avoided. Health care practitioners must understand fluid dynamic factors such as flow rate ratio, pressure and velocity gradients, and flow behavior, velocity distribution, shear stress on the wall and on blood cells. These mechanical factors are largely responsible for the deposit of blood cells and lipids, a leading cause of atherosclerosis. The interaction between blood cells and of the cells with the vessel, leads to the formation of plaques and agglomerations. These deposits are found predominantly at arterial bends and bifurcations where blood flow is disturbed, where a secondary flow is created, and where flow separation regions are found. Experiments on hemodynamic effects in elastic silicon rubber models of the cardiovascular system with flow wire, stents, or patches for vessel surgery will be discussed. These studies can be important in improving diagnostics and therapeutic applications.     

Numerical analysis of hemodynamics in spastic middle cerebral arteries

Cerebral vasospasm (CVS) is the most common serious complication of subarachnoid hemorrhage. Among the many factors that are associated with the pathogenesis of CVS, hemodynamics plays an important role in the initiation and development of CVS. Numerical simulation was carried out to obtain the flow patterns and wall shear stress (WSS) distribution in spastic middle cerebral arteries. The blood was assumed to be incompressible, laminar, homogenous, Newtonian, and steady. Our simulations reveal that flow velocity and WSS level increase at the stenosis segment of the spastic vessels, but further downstream of stenosis, the WSS significantly decreases along the inner wall, and flow circulation and stagnation are observed. The hydrodynamic resistance increases with the increase of vessel spasm. Moreover, the change of flow field and hydrodynamic forces are not linearly proportional to the spasm level, and the rapid change of hemodynamic parameters is observed as the spasm is more than 50%. Accordingly, in the view of hemodynamic physiology, vessels with less than 30% stenosis are capable of self-restoration towards normal conditions. However, vessels with more than 50% stenosis may eventually lose their capacity to adapt to differing physiologic conditions due to the extreme non-physilogic hemodynamic environment, and the immediate expansion of the vessel lumen might be needed to minimize serious and non-reversible effects.     

Differentiation of stem/progenitor cells into vascular cells in response to fluid mechanical forces

Vascular functions are regulated not only by chemical mediators, such as hormones, cytokines, and neurotransmitters, but by mechanical hemodynamic forces generated by blood flow and blood pressure. The mechanical force-mediated regulation is based on the ability of vascular cells, including endothelial cells and smooth muscle cells, to recognize fluid mechanical forces, i.e., the shear stress produced by flowing blood and the cyclic strain generated by blood pressure, and to transmit the signals into the cell interior, where they trigger cell responses that involve changes in cell morphology, cell function, and gene expression. Recent studies have revealed that immature cells, such as endothelial progenitor cells (EPCs) and embryonic stem (ES) cells, as well as adult vascular cells, respond to fluid mechanical forces. Shear stress and cyclic strain promote the proliferation and differentiation of EPCs and ES cells into vascular cells and enhance their ability to form new vessels. Even more recently, attempts have been made to apply fluid mechanical forces to EPCs and ES cells cultured on polymer tubes and develop tissue-engineered blood vessel grafts that have a structure and function similar to that of blood vessels in vivo. This review summarizes the current state of knowledge concerning the mechanobiological responses of stem/progenitor cells and its potential applications to tissue engineering.     

Wall shear stresses remain elevated in mature arteriovenous fistulas: a case study

Maintaining vascular access (VA) patency continues to be the greatest challenge for dialysis patients. VA dysfunction, primarily due to venous neointimal hyperplasia development and stenotic lesion formation, is mainly attributed to complex hemodynamics within the arteriovenous fistula (AVF). The effect of VA creation and the subsequent geometrical remodeling on the hemodynamics and shear forces within a mature patient-specific AVF is investigated. A 3D reconstructed geometry of a healthy vein and a fully mature patient-specific AVF was developed from a series of 2D magnetic resonance image scans. A previously validated thresholding technique for region segmentation and lumen cross section contour creation was conducted in MIMICS 10.01, allowing for the creation of a 3D reconstructed geometry. The healthy vein and AVF computational models were built, subdivided, and meshed in GAMBIT 2.3. The computational fluid dynamic (CFD) code FLUENT 6.3.2 (Fluent Inc., Lebanon, NH) was employed as the finite volume solver to determine the hemodynamics and shear forces within the healthy vein and patient-specific AVF. Geometrical alterations were evaluated and a CFD analysis was conducted. Substantial geometrical remodeling was observed, following VA creation with an increase in cross-sectional area, out of plane curvature (maximum angle of curvature in AVF=30?deg), and angle of blood flow entry. The mean flow velocity entering the vein of the AVF is dramatically increased. These factors result in complex three-dimensional hemodynamics within VA junction (VAJ) and efferent vein of the AVF. Complex flow patterns were observed and the maximum and mean wall shear stress (WSS) magnitudes are significantly elevated. Flow reversal was found within the VAJ and efferent vein. Extensive geometrical remodeling during AVF maturation does not restore physiological hemodynamics to the VAJ and venous conduit of the AVF, and high WSS and WSS gradients, and flow reversal persist. It is theorized that the vessel remodelling and the continued non-physiological hemodynamics within the AVF compound to result in stenotic lesion development.     

Numerical investigation of the non-Newtonian pulsatile blood flow in a bifurcation model with a non-planar branch

The pulsatile flow of non-Newtonian fluid in a bifurcation model with a non-planar daughter branch is investigated numerically by using the Carreau-Yasuda model to take into account the shear thinning behavior of the analog blood fluid. The objective of this study is to deal with the influence of the non-Newtonian property of fluid and of out-of-plane curvature in the non-planar daughter vessel on wall shear stress (WSS), oscillatory shear index (OSI), and flow phenomena during the pulse cycle. The non-Newtonian property in the daughter vessels induces a flattened axial velocity profile due to its shear thinning behavior. The non-planarity deflects flow from the inner wall of the vessel to the outer wall and changes the distribution of WSS along the vessel, in particular in systole phase. Downstream of the bifurcation, the velocity profiles are shifted toward the flow divider, and low WSS and high shear stress temporal oscillations characterized by OSI occur on the outer wall region of the daughter vessels close to the bifurcation. Secondary motions become stronger with the addition of the out-of-plane curvature induced by the bending of the vessel, and the secondary flow patterns swirl along the non-planar daughter vessel. A significant difference between the non-Newtonian and the Newtonian pulsatile flow is revealed during the pulse cycle; however, reasonable agreement between the non-Newtonian and the rescaled Newtonian flow is found. Calculated results for the pulsatile flow support the view that the non-planarity of blood vessels and the non-Newtonian properties of blood are an important factor in hemodynamics and may play a significant role in vascular biology and pathophysiology.     

Numerical analysis of flow through a severely stenotic carotid artery bifurcation

The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m2, proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-epsilon, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed.     

Numerical investigation of the non-Newtonian blood flow in a bifurcation model with a non-planar branch

The non-Newtonian fluid flow in a bifurcation model with a non-planar daughter branch is investigated by using finite element method to solve the three-dimensional Navier–Stokes equations coupled with a non-Newtonian constitutive model, in which the shear thinning behavior of the blood fluid is incorporated by the Carreau–Yasuda model. The objective of this study is to investigate the influence of the non-Newtonian property of fluid as well as of curvature and out-of-plane geometry in the non-planar daughter vessel on wall shear stress (WSS) and flow phenomena. In the non-planar daughter vessel, the flows are typified by the skewing of the velocity profile towards the outer wall, creating a relatively low WSS at the inner wall. In the downstream of the bifurcation, the velocity profiles are shifted towards the flow divider. The low WSS is found at the inner walls of the curvature and the lateral walls of the bifurcation. Secondary flow patterns that swirl fluid from the inner wall of curvature to the outer wall in the middle of the vessel are also well documented for the curved and bifurcating vessels. The numerical results for the non-Newtonian fluid and the Newtonian fluid with original Reynolds number and the corresponding rescaled Reynolds number are presented. Significant difference between the non-Newtonian flow and the Newtonian flow is revealed; however, reasonable agreement between the non-Newtonian flow and the rescaled Newtonian flow is found. Results of this study support the view that the non-planarity of blood vessels and the non-Newtonian properties of blood are an important factor in hemodynamics and may play a significant role in vascular biology and pathophysiology.     

Fluid shear stress and the vascular endothelium: for better and for worse

As blood flows, the vascular wall is constantly subjected to physical forces, which regulate important physiological blood vessel responses, as well as being implicated in the development of arterial wall pathologies. Changes in blood flow, thus generating altered hemodynamic forces are responsible for acute vessel tone regulation, the development of blood vessel structure during embryogenesis and early growth, as well as chronic remodeling and generation of adult blood vessels. The complex interaction of biomechanical forces, and more specifically shear stress, derived by the flow of blood and the vascular endothelium raise many yet to be answered questions:How are mechanical forces transduced by endothelial cells into a biological response, and is there a "shear stress receptor"?Are "mechanical receptors" and the final signaling pathways they evoke similar to other stimulus-response transduction systems?How do vascular endothelial cells differ in their response to physiological or pathological shear stresses?Can shear stress receptors or shear stress responsive genes serve as novel targets for the design of diagnostic and therapeutic modalities for cardiovascular pathologies?The current review attempts to bring together recent findings on the in vivo and in vitro responses of the vascular endothelium to shear stress and to address some of the questions raised above.     

Mechanical and hydrodynamic effects of stent expansion in tapered coronary vessels

Percutaneous coronary intervention (PCI) has become the primary treatment for patients with coronary heart disease because of its minimally invasive nature and high efficiency. Anatomical studies have shown that most coronary vessels gradually shrink, and the vessels gradually become thinner from the proximal to the distal end. In this paper, the effects of different stent expansion methods on the mechanical and hemodynamic behaviors of coronary vessels and stents were studied. To perform a structural-mechanical analysis of stent implantation, the coronary vessels with branching vessels and the coronary vessels with large bending curvature are selected. The two characteristic structures are implanted in equal diameter expansion mode and conical expansion mode, and the stress and mechanical behaviors of the coronary vessels and stents are analyzed. The results of the structural-mechanical analysis showed that the mechanical behaviors and fatigue performance of the cobalt-chromium alloy stent were good, and the different expansion modes of the stent had little effect on the fatigue performance of the stent. However, the equal diameter expansion mode increased distal coronary artery stress and the risk of vascular injury. The computational fluid dynamics analysis results showed that different stent expansion methods had varied effects on coronary vessel hemodynamics and that the wall shear stress distribution of conical stent expansion is more uniform compared with equal diameter expansion. Additionally, the vortex phenomenon is not apparent, the blood flow velocity is slightly increased, the hydrodynamic environment is more reasonable, and the risk of coronary artery injury is reduced.

     

Effects of bradykinin on the hemodynamics of tumor and granulating normal tissue microvasculature.

Bradykinin (BK) is an important endogenous mediator of microvascular flow modulation. Since the structure of the microcirculation is very different in tumor tissues than in normal tissues, bradykinin may elicit different responses in tumors. This study was designed to test the hypothesis that local administration of bradykinin increases blood flow preferentially in normal tissue relative to adjacent tumor tissue, resulting in a "vascular steal" phenomenon. Microvessel diameters (D), velocities (Vc), length densities, shear rates, and intermittent flow frequencies were measured every 10 min before, during, and after 40 min exposure to BK in rats with dorsal flap window chambers 9 days after tumor implantation. Separate studies were made of normal vessels outside the tumor margin, the hypervascular tumor periphery, and the tumor center. Bradykinin was administered with a suffusion medium flowing over the tissue at 1-2 ml/min with a BK concentration of 1.6 x 10(7) M. Administration of BK created five distinct changes in normal and tumor vessel function that varied over time, but coincidentally reached a maximum effect after 20 min exposure to BK. In normal vessels, increased Vc and D led to increased flow, which reached a peak 20 min after onset of suffusion with BK. In contrast, in centrally located tumor vessels, decreased D and Vc were observed in most vessels during the initial 10-20 min of suffusion. In addition, there was a significant increase in intermittent flow frequency in tumor central vessels, which peaked after 20 min of suffusion with BK. These five separate observations that coincided at 20 min of suffusion are consistent with a "vascular steal" phenomenon. The increase in normal microvessel D and Vc at 20 min suggests that BK causes vasodilation in arterioles. The coincident decrease in tumor microvessel D and Vc suggests that tumor feeding vessels are less able to respond to BK by vasodilating. The concomitant increase in intermittent flow frequency in tumor vessels suggests that a reduction in pressure drop occurred after 20 min exposure to BK, which is also consistent with "vascular steal." Since BK is also known to increase vascular permeability, it is possible that increases in interstitial fluid pressure brought on by exposure to BK contributed to the observed reduction in tumor blood flow. In normal vessels, reduced D and Vc, relative to peak values, were noted after 40 min suffusion with BK. Adherence of leukocytes to the vessel walls was prominent and microthrombi were also observed during this period. No evidence of such adhesion was seen in tumor vessels, although microthrombi were observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

A novel technology for large vessel recanalization

Large vessels recanalization is a challenge for mechanical atherectomy devices, where the lumen debulked is close in diameter to the device crossing profile, which may be only 25% to 30% of the original lumen size; so, the procedure can restore only a fraction of the original blood flow. Moreover, small diameter lumens are prone to be repeatedly occluded after a relatively short period of time. In this article, we present a novel technology of recanalization, using a catheter-based microjet system to deliver a flux of biocompatible abrasive particles to the lesion site, resulting in microchipping of the plaque, while minimizing trauma to the vessel wall. Plaque debris is removed from the blood flow, and blood flow is restored. In contrast to rotating mechanical devices, plaque debulking can be performed up to diameters that are substantially larger than the device crossing profile, supporting superior long-term patency. As a case study, we evaluated the technology for use in the superficial femoral artery where the lesions tend to be very long and heavily calcified with high restenosis rates.     

A constrained mixture model for developing mouse aorta

Mechanical stresses influence the structure and function of adult and developing blood vessels. When these stresses are perturbed, the vessel wall remodels to return the stresses to homeostatic levels. Constrained mixture models have been used to predict remodeling of adult vessels in response to step changes in blood pressure, axial length and blood flow, but have not yet been applied to developing vessels. Models of developing blood vessels are complicated by continuous and simultaneous changes in the mechanical forces. Understanding developmental growth and remodeling is important for treating human diseases and designing tissue-engineered blood vessels. This study presents a constrained mixture model for postnatal development of mouse aorta with multiple step increases in pressure, length and flow. The baseline model assumes that smooth muscle cells (SMCs) in the vessel wall immediately constrict or dilate the inner radius after a perturbation to maintain the shear stress and then remodel the wall thickness to maintain the circumferential stress. The elastin, collagen and SMCs have homeostatic stretch ratios and passive material constants that do not change with developmental age. The baseline model does not predict previously published experimental data. To approximate the experimental data, it must be assumed that the SMCs dilate a constant amount, regardless of the step change in mechanical forces. It must also be assumed that the homeostatic stretch ratios and passive material constants change with age. With these alterations, the model approximates experimental data on the mechanical properties and dimensions of aorta from 3- to 30-day-old mice.     

In vivo two-photon excited fluorescence microscopy reveals cardiac- and respiration-dependent pulsatile blood flow in cortical blood vessels in mice

Subtle alterations in cerebral blood flow can impact the health and function of brain cells and are linked to cognitive decline and dementia. To understand hemodynamics in the three-dimensional vascular network of the cerebral cortex, we applied two-photon excited fluorescence microscopy to measure the motion of red blood cells (RBCs) in individual microvessels throughout the vascular hierarchy in anesthetized mice. To resolve heartbeat- and respiration-dependent flow dynamics, we simultaneously recorded the electrocardiogram and respiratory waveform. We found that centerline RBC speed decreased with decreasing vessel diameter in arterioles, slowed further through the capillary bed, and then increased with increasing vessel diameter in venules. RBC flow was pulsatile in nearly all cortical vessels, including capillaries and venules. Heartbeat-induced speed modulation decreased through the vascular network, while the delay between heartbeat and the time of maximum speed increased. Capillary tube hematocrit was 0.21 and did not vary with centerline RBC speed or topological position. Spatial RBC flow profiles in surface vessels were blunted compared with a parabola and could be measured at vascular junctions. Finally, we observed a transient decrease in RBC speed in surface vessels before inspiration. In conclusion, we developed an approach to study detailed characteristics of RBC flow in the three-dimensional cortical vasculature, including quantification of fluctuations in centerline RBC speed due to cardiac and respiratory rhythms and flow profile measurements. These methods and the quantitative data on basal cerebral hemodynamics open the door to studies of the normal and diseased-state cerebral microcirculation.     

Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. Although exact causes and mechanisms of AV calcification are unclear, previous studies suggest that mechanical forces play a role. Since calcium deposits occur almost exclusively on the aortic surfaces of AV leaflets, it has been hypothesized that adverse patterns of fluid shear stress on the aortic surface of AV leaflets promote calcification. The current study characterizes AV leaflet aortic surface fluid shear stresses using Laser Doppler velocimetry and an in vitro pulsatile flow loop. The valve model used was a native porcine valve mounted on a suturing ring and preserved using 0.15% glutaraldehyde solution. This valve model was inserted in a mounting chamber with sinus geometries, which is made of clear acrylic to provide optical access for measurements. To understand the effects of hemodynamics on fluid shear stress, shear stress was measured across a range of conditions: varying stroke volumes at the same heart rate and varying heart rates at the same stroke volume. Systolic shear stress magnitude was found to be much higher than diastolic shear stress magnitude due to the stronger flow in the sinuses during systole, reaching up to 20 dyn/cm² at mid-systole. Upon increasing stroke volume, fluid shear stresses increased due to stronger sinus fluid motion. Upon increasing heart rate, fluid shear stresses decreased due to reduced systolic duration that restricted the formation of strong sinus flow. Significant changes in the shear stress waveform were observed at 90 beats/min, most likely due to altered leaflet dynamics at this higher heart rate. Overall, this study represents the most well-resolved shear stress measurements to date across a range of conditions on the aortic side of the AV. The data presented can be used for further investigation to understand AV biological response to shear stresses.     

IVUS-based computational modeling and planar biaxial artery material properties for human coronary plaque vulnerability assessment

Image-based computational modeling has been introduced for vulnerable atherosclerotic plaques to identify critical mechanical conditions which may be used for better plaque assessment and rupture predictions. In vivo patient-specific coronary plaque models are lagging due to limitations on non-invasive image resolution, flow data, and vessel material properties. A framework is proposed to combine intravascular ultrasound (IVUS) imaging, biaxial mechanical testing and computational modeling with fluid-structure interactions and anisotropic material properties to acquire better and more complete plaque data and make more accurate plaque vulnerability assessment and predictions. Impact of pre-shrink-stretch process, vessel curvature and high blood pressure on stress, strain, flow velocity and flow maximum principal shear stress was investigated.     

Effect of a lipid pool on stress/strain distributions in stenotic arteries: 3-D fluid-structure interactions (FSI) models

Nonlinear 3-D models with fluid-structure interactions (FSI) based on in vitro experiments are introduced and solved by ADINA to perform flow and stress/strain analysis for stenotic arteries with lipid cores. Navier-Stokes equations are used as the governing equations for the fluid. Hyperelastic Mooney-Rivlin models are used for both the arteries and lipid cores. Our results indicate that critical plaque stress/strain conditions are affected considerably by stenosis severity, eccentricity, lipid pool size, shape and position, plaque cap thickness, axial stretch, pressure, and fluid-structure interactions, and may be used for possible plaque rupture predictions.     

CFD analysis of pulsatile blood flow in an atherosclerotic human artery with eccentric plaques

Atherosclerosis is a slow vascular degeneration. It thickens the internal walls of a blood vessel locally depositing an atherosclerotic plaque. Such reduced lumen increases the resistance to blood flow. Plaques can be punctual (eccentric, here considered) or circumferential (symmetrical). Stenoses do not have a typical shape: we hypothesised here a reference geometry (trapezium) with its possible evolutions (semi-ellipse, triangle). Two criteria (Equivalent Area and Equivalent Dimensions) were then defined to compare the results among the 35 case studies numerically analysed with a Computational Fluid Dynamics code (Comsol Multiphysics 3.3). Blood was considered a Cassonian fluid with modified viscosity equation. The artery was cylindrical, rigid and straight, interested by a pulsatile blood flow. Among the variables: shape and dimensions of the stenoses; number of stenoses (single or coupled pathologies); mutual locations (3 possibilities). The main results were that the length of the consequent flow disturbance is due to the stenotic shape and height; blood flow recirculation, downstream of the pathology, is due to the slope of the stenotic walls; and the peak velocities depend on the shape and height of stenosis. The differences from case to case diminish in diastole.     

Measuring hemodynamic changes during mammalian development

The pathogenesis of many congenital cardiovascular diseases involves abnormal flow within the embryonic vasculature that results either from malformations of the heart or defects in the vasculature itself. Extensive genetic and genomic analysis in mice has led to the identification of an array of mutations that result in cardiovascular defects during embryogenesis. Many of these mutations cause secondary effects within the vasculature that are thought to arise because of altered fluid dynamics. Presumably, cardiac defects disturb or reduce flow and thereby lead to the disruption of the mechanical signals necessary for proper vascular development. Unfortunately, a precise understanding of how flow disruptions lead to secondary vasculature defects has been hampered by the inadequacy of existing analytical tools. Here, we used a fast line-scanning technique for the quantitative analysis of hemodynamics during early organogenesis in mouse embryos, and we present a model system for studying cellular responses during the formation and remodeling of the mammalian cardiovascular system. Flow velocity profiles can be measured as soon as a heart begins to beat even in newly formed vessels. These studies establish a link between the pattern of blood flow within the vasculature and the stage of heart development and also enable analysis of the influence of mechanical forces during development.     

Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall

Experimental data of the radial incorporation of labeled cholesterol [¹⁴C-4] into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfusedin vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of [¹⁴C-4] activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity,D and solute filtration velocity,V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work.