Non-Newtonian effects of blood flow on hemodynamics in distal vascular graft anastomoses

Non-Newtonian fluid flow in a stenosed coronary bypass is investigated numerically using the Carreau-Yasuda model for the shear thinning behavior of the blood. End-to-side coronary bypass anastomosis is considered in a simplified model geometry where the host coronary artery has a 75% severity stenosis. Different locations of the bypass graft to the stenosis and different flow rates in the graft and in the host artery are studied. Particular attention is given to the non-Newtonian effect of the blood on the primary and secondary flow patterns in the host coronary artery and the wall shear stress (WSS) distribution there. Interaction between the jet flow from the stenosed artery and the flow from the graft is simulated by solving the three-dimensional Navier-Stokes equation coupled with the non-Newtonian constitutive model. Results for the non-Newtonian flow, the Newtonian flow and the rescaled Newtonian flow are presented. Significant differences in axial velocity profiles, secondary flow streamlines and WSS between the non-Newtonian and Newtonian fluid flows are revealed. However, reasonable agreement between the non-Newtonian and the rescaled Newtonian flows is found. Results from this study support the view that the residual flow in a partially occluded coronary artery interacts with flow in the bypass graft and may have significant hemodynamic effects in the host vessel downstream of the graft. Non-Newtonian property of the blood alters the flow pattern and WSS distribution and is an important factor to be considered in simulating hemodynamic effects of blood flow in arterial bypass grafts.     

A simple fluid-structure coupling algorithm for the study of the anastomotic mechanics of vascular grafts

Vascular anastomoses constitute a main factor in poor graft performance due to mismatches in distensibility between the host artery and the graft. This work aims at computational fluid-structure investigations of proximal and distal anastomoses of vein grafts and synthetic grafts. Finite element and finite volume models were developed and coupled with a user-defined algorithm. Emphasis was placed on the simplicity of the coupling algorithm. An artery and vein graft showed a larger dilation mismatch than an artery and synthetic graft. The vein graft distended nearly twice as much as the artery while the synthetic graft displayed only approximately half the arterial dilation. For the vein graft, luminal mismatching was aggravated by development of an anastomotic pseudo-stenosis. While this study focused on end-to-end anastomoses as a vehicle for developing the coupling algorithm, it may serve as useful point of departure for further investigations such as other anastomotic configurations, refined modelling of sutures and fully transient behaviour.     

Fluid flow structure in arterial bypass anastomosis

The fluid flow through a stenosed artery and its bypass graft in an anastomosis can substantially influence the outcome of bypass surgery. To help improve our understanding of this and related issues, the steady Navier-Stokes flows are computed in an idealized arterial bypass system with partially occluded host artery. Both the residual flow issued from the stenosis--which is potentially important at an earlier stage after grafting--and the complex flow structure induced by the bypass graft are investigated. Seven geometric models, including symmetric and asymmetric stenoses in the host artery, and two major aspects of the bypass system, namely, the effects of area reduction and stenosis asymmetry, are considered. By analyzing the flow characteristics in these configurations, it is found that (1) substantial area reduction leads to flow recirculation in both upstream and downstream of the stenosis and in the host artery near the toe, while diminishes the recirculation zone in the bypass graft near the bifurcation junction, (2) the asymmetry and position of the stenosis can affect the location and size of these recirculation zones, and (3) the curvature of the bypass graft can modify the fluid flow structure in the entire bypass system.     

A simple fluid–structure coupling algorithm for the study of the anastomotic mechanics of vascular grafts

Vascular anastomoses constitute a main factor in poor graft performance due to mismatches in distensibility between the host artery and the graft. This work aims at computational fluid–structure investigations of proximal and distal anastomoses of vein grafts and synthetic grafts. Finite element and finite volume models were developed and coupled with a user-defined algorithm. Emphasis was placed on the simplicity of the coupling algorithm. An artery and vein graft showed a larger dilation mismatch than an artery and synthetic graft. The vein graft distended nearly twice as much as the artery while the synthetic graft displayed only approximately half the arterial dilation. For the vein graft, luminal mismatching was aggravated by development of an anastomotic pseudo-stenosis. While this study focused on end-to-end anastomoses as a vehicle for developing the coupling algorithm, it may serve as useful point of departure for further investigations such as other anastomotic configurations, refined modelling of sutures and fully transient behaviour.     

A model of stress-induced geometrical remodeling of vessel segments adjacent to stents and artery/graft anastomoses

The mismatch between the elastic properties and initial geometry of a host artery and an implanted stent or graft cause significant stress concentration at the zones close to junctions. This may contribute to the often observed intimal hyperplasia, resulting in late lumen loss and eventual restenosis. This study proposes a mathematical model for stress-induced thickening of the arterial wall at the zones close to an implanted stent or graft. The host artery was considered initially as a cylindrical shell with constant thickness that was clamped to the stent or graft, which was assumed to be non-deformable in the circumferential direction. It was assumed that the abnormal circumferential and axial stresses due to the bending of the arterial wall cause wall thickening that tends to restore the stress state close to that existing far from the junction. The linear equations of a cylindrical shell with variable thickness were coupled to an evolution equation for the wall thickness. These equations were solved numerically and a parametric study was performed using finite difference method and explicit time step. The results show that the remodeling process is self-limiting and leads to local thickening that gradually decreases with distance from the edge of the stent/graft. Model predictions were tested against morphological findings existing in the literature. Recommendations on stent designs that reduce stress concentrations are discussed.     

Effects of compliance mismatch on blood flow in an artery with endovascular prosthesis

The objective of this paper is to study the mechanical effects caused by the local stiffening of an artery (due to the vascular prosthesis, for instance). At the junction of the host artery and the more rigid implantant, the abrupt change in compliance creates an abnormal stress concentration that initiates an adaptive response in the vascular tissue. The roles of both fluid and solid mechanical phenomena must be considered in the prosthesis design optimization. In this context, even the simple models could provide helpful tools for designing process. We present here a model of blood flow in compliant vessel. The artery is supposed to be an orthotropical thin elastic shell. We obtain the solution by matched asymptotic expansions. The results prove the high flexure concentration close to the compliance jump. It is shown that the use of orthotropical graft may reduce the peak value of these shear forces to a remarkable extent. Waves reflected from the suture and pressure increase in the prosthesis are discussed. Compliance mismatch is shown to reduce the peak value of maximal wall shear stress.     

A mathematical assessment of suture line stress in the end-to-side anastomosis—I. Steady flow

The tensile force acting on the suture line connecting a synthetic graft to a host artery in an end-to-side anastomosis is shown to increase from 23,000 to 55,000 dyn as the ratio of the graft-artery area increased from 0.5 to 1.2. The angle of the end-to-side anastomosis is shown to have negligible effect on the suture line stress. The stresses calculated for 3-0. Tevdek suture subjected to the above forces are shown to be one-fiftieth of the yield strength of that suture material. However, it is suggested that such suture forces could cause the suture to tear through the host arterial wall unless sufficient sutures per cm, and maximum suture-host artery contact area are established.     

The role of cell proliferation and migration in the development of a neo-intimal layer in veins grafted into arteries,in rats

Summary The development of a thickened (hyperplastic) fibro-cellular neo-intima is a significant event in the adaptation of a vein grafted into an artery. The histogenesis of tissues in vein grafts was explored in a rat model where the source of endothelial and smooth muscle cells was from the adjacent artery. Cell proliferation was assessed by the incorporation of tritiated thymidine and autoradiography, up to 18 months after grafting. Cell migration was detected by prelabelling in the first 5 days after grafting and sampling at later times. The proliferation of cells in the arterial media adjacent to the graft was elevated above control levels as early as 2 days after grafting; it was maximal at 3 days and returned to low levels by day 21. During the first week, prelabelled smooth muscle cells in the tunica media of the adjacent artery migrated to the subendothelial space, where they continued to proliferate to produce arterial intimal hyperplasia. The migration of endothelial and smooth muscle cells proceeded across the anastomosis to populate the vein graft neo-intima, where smooth muscle cells continued to proliferate until 28 days after grafting. Cell migration and proliferation were significant factors in the histogenesis of vein graft neo-intimal hyperplasia in this model. These processes were controlled, perhaps by local regulatory factors, to form a vein graft, the wall of which was similar in thickness and structure to that of the host artery.     

Relative contribution of wall shear stress and injury in experimental intimal thickening at PTFE end-to-side arterial anastomoses

BACKGROUND: Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS: The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS: The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.     

That hemodynamics and not material mismatch is of primary concern in bypass graft failure: an experimental argument

The long term patency of end-to-side peripheral artery bypasses are low due to failure of the graft generally at the distal end of the bypass. Both material mismatch between the graft and the host artery and junction hemodynamics are cited as being major factors in disease formation at the junction. This study uses experimental methods to investigate the major differences in fluid dynamics and wall mechanics at the proximal and distal ends for rigid and compliant bypass grafts. Injection moulding was used to produce idealized transparent and compliant models of the graft/ artery junction configuration. An ePTFE graft was then used to stiffen one of the models. These models were then investigated using two-dimensional video extensometry and one-dimensional laser Doppler anemometry to determine the junction deformations and fluid velocity profiles for the rigid and complaint graft anastomotic junctions. Junction strains were evaluated and generally found to be under 5% with a peak stain measured in the stiff graft model junction of 8.3% at 100 mmHg applied pressure. Hemodynamic results were found to yield up to 40% difference in fluid velocities for the stiff/compliant comparison but up to 80% for the proximal/distal end comparisons. Similar strain conditions were assumed for the proximal and distal models while significant differences were noted in their associated hemodynamic changes. In contrasting the fluid dynamics and wall mechanics for the proximal and distal anastomoses, it is evident from the results of this study, that junction hemodynamics are the more variable factor.     

Functional properties of fresh and cryopreserved carotid and femoral arteries,and of venous and synthetic grafts: comparison with arteries from normotensive and hypertensive patients

The ideal arterial graft must share identical functional properties with the host artery. Surgical reconstruction of the common carotid artery (CA) is performed in several clinical situations, using expanded polytetrafluoroethylene prosthesis (ePTFE) or saphenous vein (SV) grafts. At date there is interest in obtaining an arterial graft that improves the results of that nowadays available. The use of a fresh or cryopreserved/defrosted artery appears as an interesting alternative. However, if the fresh and cryopreserved/defrosted arteries allow an adequate viscoelastic and functional matching with the host arteries needs to be established. The aims were to compare the viscoelastic and functional performance of: (1) conduits used in CA reconstruction (SV and ePTFE) with those of the fresh and cryopreserved/defrosted CA and femoral arteries (FA), and (2) normotensive and hypertensive patients’ arteries with those of the arterial substitutes in vitro analyzed. Pressure, diameter and wall thickness of the CA were recorded in 15 normotensive and 15 hypertensive patients (in vivo studies), and in SV, fresh and cryopreserved/defrosted CA and FA (obtained from 15 donors), and ePTFE segments (in vitro studies). From stress–strain relationship we calculated elastic and viscous modulus, and the characteristic impedance. The local buffer and conduit functions were quantified as the viscous/elastic quotient and the inverse of the characteristic impedance. Fresh and cryopreserved/defrosted CA and FA were more alike, both in viscoelastic and functional levels, respect to normotensive and hypertensive patients’ arteries, than the ePTFE and SV grafts. CA and FA cryografts could be considered an important alternative for carotid reconstruction.     

Does PGA external stenting reduce compliance mismatch in venous grafts?

Background  

Autogenous vein grafting is widely used in regular bypassing procedures. Due to its mismatch with the host artery in both mechanical property and geometry, the graft often over expands under high arterial blood pressure and forms a step-depth where eddy flow develops, thus causing restenosis, fibrous graft wall, etc. External stents, such as sheaths being used to cuff the graft, have been introduced to eliminate these mismatches and increase the patency. Although histological and immunochemical studies have shown some positive effects of the external stent, the mechanical mismatch under the protection of an external stent remains poorly analyzed.     

犬不同血管搭桥方法及搭桥血管内流场的计算机数值模拟

目的血管搭桥术后的内膜增生往往导致手术失败,而内膜增生与搭桥血管内的流场密切相关,为改善搭桥血管中的流场结构,作者设计了偏心搭桥手术方法,利用计算机数值模拟技术,探索偏心搭桥和传统搭桥血管中流场的变化,为血管搭桥方法提供优化设计方案。方法16只犬随机分为偏心搭桥组和传统搭桥组进行血管搭桥,测定搭桥前后血管几何数据,搭桥后近心端及远心端吻合口血流量和血压。按测定的血管几何数据,FLUENT 6.2模拟搭桥血管内的流场。结果偏心搭桥近心端和远心端吻合口不在同一平面。传统搭桥中,主体动脉远心端吻合口对应面处存在一个较低壁面剪切应力（WSS）区域及流体停滞点,离脚跟较近的一部分流体会形成涡漩,血流进入主体动脉后,还会表现出迪恩涡二次流;偏心搭桥中,主体动脉吻合口对应面上的低WSS区域和流体停滞点消失,血流接触到吻合口底面后,以切向旋转的方式改变其流动方向,不会形成涡漩,且当血流进入主体动脉后,立即发生螺旋流态且能持续很长一段。结论偏心搭桥能够产生血液旋动流,显著增加远心端血流量、提高WSS。     

Extensor digitorum brevis free flap: anatomic study and further clinical applications

The extensor digitorum brevis muscle flap is reliable, safe, and can be used either as a pedicle or as a free flap with minimal donor site morbidity. To increase the existing knowledge of this flap and to establish further anatomic basis for the design and elevation of the extensor digitorum brevis flap, 26 specimens from 13 fresh cadavers were dissected under 3.5x loupes. The lateral tarsal artery was found to be the main blood supply to the muscle. It has an average diameter of 1.83+/-0.35 mm and a length of 1.89+/-0.69 cm. The dorsalis pedis artery has, at the level of the lateral tarsal artery takeoff, a diameter of 3.25+/-0.62 mm. From this point to the origin of the deep plantar branch, the dorsalis pedis artery has minimal branching, and the surgeon has available an artery homogeneous in diameter that is 6.77+/-0.99 cm in length. Related neurovascular structures (anterior tibial artery and the venae comitantes, dorsalis pedis and first dorsal metatarsal artery, and deep peroneal nerve) were also studied. A safe and reliable harvesting technique and the "T interposed extensor digitorum brevis" technique for sparing the anterior tibial artery are presented, as are clinical case examples on the use of this flap as a flow-through, extensor digitorum brevis-vascularized nerve graft, a combined extensor digitorum brevis-deep peroneal nerve graft, and a bilobed extensor digitorum brevis-dorsalis pedis fasciosubcutaneous free flap.     

Automated classification of peripheral distal by-pass geometries reconstructed from medical data

Abnormal haemodynamic conditions are implicated in the development of anastomotic myointimal hyperplasia (MIH). However, these conditions are difficult to determine in vivo, prompting research using ex vivo idealised models. To relate the understanding gained in idealised geometries to anatomically correct conditions we have investigated a reproducible approach to classify in vivo distal graft anastomoses and their inter-patient variability. In vivo distal anastomotic geometries were acquired by magnetic resonance (MR) angiography from 13 patients who had undergone infrageniculate autologous venous by-pass surgery. On average, the images were acquired 2 weeks post-operatively. Five patients also underwent repeat examinations 2 to 7 weeks later. For each geometry, the surface of the arterial lumen is represented by the zero level set of an implicit function constructed from radial basis functions that minimise curvature. The three-dimensional binary image created from the interpolated surface is processed using a skeletonisation algorithm to obtain the centreline of each branch in the geometry. This allows for the measurement of the branching angles between straight line approximations of the centrelines of each vessel, averaging them over a characteristic length of each anastomosis. The main finding in the application of the proposed classification methodology to this set of patients is that the spectrum of anastomoses can be reduced to a small subset of cases characterised by two angles: the angle between the graft and the plane of the host artery and the angle between the graft and the proximal branch of the artery.     

Visualizing the innate and adaptive immune responses underlying allograft rejection by two-photon microscopy

Transplant rejection involves a coordinated attack of the innate and the adaptive immune systems of the host. To investigate this dynamic process and the contributions of both donor and host cells, we developed an ear skin graft model suitable for intravital imaging. We found that donor dermal dendritic cells (DCs) migrated rapidly from the graft and were replaced by host CD11b(+) mononuclear cells. The infiltrating host cells captured donor antigen, reached the draining lymph node and cross-primed graft-reactive CD8(+) T cells. Furthermore, we defined the mechanisms by which host T cells target graft cells. We found that primed T cells entered the graft from the surrounding tissue and localized selectively at the dermis-epidermis junction. Later, CD8(+) T cells disseminated throughout the graft and many became arrested. These results provide insights into the antigen presentation pathway and the stepwise progression of CD8(+) T cell activity, thereby offering a framework for evaluating how immunotherapy might abrogate the key steps in allograft rejection.     

Tri-layered Electrospinning to Mimic Native Arterial Architecture using Polycaprolactone,Elastin, and Collagen: A Preliminary Study

Throughout native artery, collagen and elastin play an important role, providing a mechanical backbone, preventing vessel rupture, and promoting recovery under pulsatile deformations. The goal of this study was to mimic the structure of native artery by fabricating a multi-layered electrospun conduit composed of poly(caprolactone) (PCL) with the addition of elastin and collagen with blends of 45-45-10, 55-35-10, and 65-25-10 PCL-ELAS-COL to demonstrate mechanical properties indicative of native arterial tissue, while remaining conducive to tissue regeneration. Whole grafts and individual layers were analyzed using uniaxial tensile testing, dynamic compliance, suture retention, and burst strength. Compliance results revealed that changes to the middle/medial layer changed overall graft behavior with whole graft compliance values ranging from 0.8 - 2.8 % / 100 mmHg, while uniaxial results demonstrated an average modulus range of 2.0 - 11.8 MPa. Both modulus and compliance data displayed values within the range of native artery. Mathematical modeling was implemented to show how changes in layer stiffness affect the overall circumferential wall stress, and as a design aid to achieve the best mechanical combination of materials. Overall, the results indicated that a graft can be designed to mimic a tri-layered structure by altering layer properties.     

Split tolerance induced by chick embryo thymic epithelium allografted to embryonic recipients

To test the capacity of the epithelial component of the chick embryo thymus to induce tolerance to major histocompatibility complex (MHC) antigens, pre-colonized thymic rudiments were grafted into chick embryonic recipients. Semi-allogeneic or allogeneic transplantations were done between two lines of chickens histocompatible at the MHC locus. Approximately 10% of these thymic chimeras hatched and were studied 3 mo after hatching. Thymic grafts were not rejected by the allogeneic host. The tolerance of chimeric chickens to thymus donor MHC antigens was tested by using a skin graft rejection test and a graft-vs-host (GvH) assay. Chimeric chickens that received an MHC-incompatible thymic graft during the embryonic life tolerated skin graft with the MHC haplotype of the thymus donor. Nevertheless, the lymphocytes within the thymic graft, the host thymus, and the blood were tolerant to the host MHC antigens but were alloreactive in GvH reaction for the MHC antigens of the thymic graft type. These results suggest that the epithelial component of the thymus when taken before the starting of the colonization by hemopoietic precursors and grafted into an early chick embryonic host can induce a tolerance for the MHC determinants involved in allograft rejection but not in the GvH reaction.     

Applying elastic fibre biology in vascular tissue engineering

For the treatment of vascular disease, the major cause of death in Western society, there is an urgent need for tissue-engineered, biocompatible, small calibre artery substitutes that restore biological function. Vascular tissue engineering of such grafts involves the development of compliant synthetic or biomaterial scaffolds that incorporate vascular cells and extracellular matrix. Elastic fibres are major structural elements of arterial walls that can enhance vascular graft design and patency. In blood vessels, they endow vessels with the critical property of elastic recoil. They also influence vascular cell behaviour through direct interactions and by regulating growth factor activation. This review addresses physiological elastic fibre assembly and contributions to vessel structure and function, and how elastic fibre biology is now being exploited in small diameter vascular graft design.     

Comparison of methods of temperature measurement in swine

The purpose of these experiments was to test the equivalence of pulmonary artery, urinary bladder, tympanic, rectal and femoral artery methods of temperature measurement in healthy and critically ill swine under clinical intensive care unit (ICU) conditions using a prospective, time series design. First, sensors were tested for error and sensitivity to change in temperature with a precision-controlled water bath and a laboratory-certified digital thermometer for temperatures 34-42 degrees C. There was virtually no systematic (bias) or random (precision) error (<0.2 degrees C). The bladder sensor had the slowest response time to change in temperature (105-120 s). Next, testing was done in an experimental porcine ICU in a non-profit research institution with four male, sedated, and mechanically ventilated domestic farm pigs. The in vivo experiments were conducted over periods of 41-168 h with temperatures measured every 1-5 s. The bladder, tympanic and rectal methods had unacceptable bias (>or=0.5 degrees C) and/or precision (>or=0.2 degrees C). Response time varied from 7 s with the femoral artery method to 280 s (4.7 min) with the tympanic method. We concluded that equivalence of the methods was insufficient for them to be used interchangeably in the porcine ICU. Intravascular monitoring of core body temperature produces optimal measurement of porcine temperature under varying conditions of physiological stability.