Distal Anastomotic Intimal Hyperplasia Research Articles

Evaluation of a novel vascular graft with a distal bifurcation designed to reduce the development of intimal hyperplasia. Experimental study in a porcine aorta model

Abnormal haemodynamics is commonly agreed to be a major contributor to the development of distal anastomotic intimal hyperplasia. A new vascular graft design proposed by computational studies was used to demonstrate its surgical feasibility and to compare it with the conventional graft in a porcine model. The device was used in 12 eight-month-old pigs, six received the new graft and six had a conventional graft. The proximal graft end was implanted into the aorta, the distal graft end was implanted into the iliac artery. The host artery was ligated in order to simulate occlusion. At 20 weeks after surgery the pigs were killed and the device was excised for histological and morphometric analysis. In five experimental grafts the reconstruction was occluded due to thrombosis; only one prosthesis was patent showing a minimum of neointimal hyperplasia. In the control group too only three of the six grafts were patent. A histological analysis revealed, as the cause of occlusion, fibrous tissue overgrowth corresponding in structure to neointimal hyperplasia. Differences in the number of obliterations and in occlusion rates between the profiles of the two groups were evaluated using the median test (P<0.05). The results were not statistically significant. Although mathematical modelling had shown significant haemodynamic benefits of a naturally bifurcated graft, our study did not confirm its superiority over conventionally used prostheses.

Distal Anastomotic Intimal Hyperplasia: Histocytomorphology, Pathophysiology, Etiology, and Prevention.

The ubiquitous relationship of late graft occlusion, particularly the nonautogenous bypasses and distal anastomotic intimal hyperplasia (DAIH), has been extensively investigated. After having established the specific location of DAIH in human autogenous, biologic and prosthetic late graft occlusion, canine models were designed to elucidate the role of compliance mismatch between graft and the host artery and the configuration of the distal end to side versus end to end anastomosis using autogenous artery. DAIH occurred in all end to side anastomosis but not in side matching end to end anastomosis. Compliance mismatched is not the cause of DAIH development, but it enhances the pathogenesis. Further study using pharmacologic agents to modulate the activities of vascular myoblasts was successful in attenuating DAIH development and progression. Since DAIH occurs through a cascade of events initiated by endothelial lifting of the overlapping processes at the gap junction to allow blood borne elements to enter the subendothelial space, then incites myoblast proliferation and matrix synthesis leading to DAIH formation at the heel and toe where oscillatory flow exists. Control of myoblast activity is needed on a permanent basis to prevent DAIH development and progression. Cessation of treatment allows resurgence of DAIH biogenesis. Direct regulation of vascular myoblast activity preclude the need of inhibiting other source of stimuli that increases as our knowledge of the subject grows. Without the participation of myoblast, there will be no DAIH irrespective of the potency and numbers of enzymatic, hormonal, or mechanical inciting factors. DAIH is a byproduct of oscillatory flow at the heel and the toe which enable blood borne elements to enter subendothelial space via the gap junction subsequent to lifting of endothelial cell overlapping processes. Pharmacologic control aiming at inactivating the myoblast in proliferation and matrix synthesis is a logical mode to control DAIH formation and late graft failure. Our experimental models confirm the success in controlling DAIH using heparin fraction that lack the anticoagulant yet is active in antiproliferative effect on myoblasts.

Effects of Batroxobin on distal anastomotic intimal hyperplasia after expanded polytetrafluoroethylene bypass grafting in dog common carotid artery

To study the morphological behavior, the expression of MCP-1 and PDGF-B of distal anastomotic neointima after expanded polytetrafluoroethylene (ePTFE) bypass grafting. And to identify the effects of Batroxobin (BX) on distal anastomotic intimal hyperplasia. 12 adult mongrel dogs underwent end to side bypass grafting in left common carotid artery using ePTFE vascular graft (6mm in diameter, 5cm in length) were divided randomly into two groups. All 12 bypass grafts were removed 28 days after grafting and distal anastomotic parts were obtained. Using HE, Masson, IHC, RT-PCR and western blot, we analyzed the thickness, relative content of ECM, SMC PCNA index, expression of MCP-1 and PDGF-B in distal anastomotic neointima. And we compared the differences between the two groups. 28 day after grafting, the neointima was formed by SMC and ECM and was covered by epithelial cells. After using BX, the thickness of neointima was reduced [( 381.3 +/- 144.7) microm versus (213.8 +/- 29.0) microm, P < 0.05] and the relative content of ECM were significantly decreased (P = 0.006). The PCNA index (P = 0.109) and PDGF-B level (P = 0.055 by RT-PCR and P = 0.337 by WB) between the two groups had no significant difference. MCP-1 level was markedly decreased (P = 0.025 by RT-PCR and P = 0.016 by WB). Using BX after ePTFE grafting could effectively reduce the relative content of ECM, reduce the expression of MCP-1 and decrease the thickness of neointima in the early time.

Inhibition of anastomotic intimal hyperplasia using a chimeric decoy strategy against NF B and E2F in a rabbit model

Neointimal formation remains a major limitation after arterial reconstruction. To overcome this problem, we focused on two important transcription factors, nuclear factor-kappaB (NFkappaB) and E2F. The purpose of this study was to determine the effects of simultaneous inhibition of these transcription factors on the formation of neointimal hyperplasia. We employed chimeric decoy oligodeoxynucleotides (ODN) to inhibit both NFkappaB and E2F simultaneously, and examined the effects of chimeric decoy ODN on the proliferation and migration of cultured vascular cells and on the formation of neointimal hyperplasia using prosthetic graft placement in a rabbit hypercholesterolemia model. Our in vitro study demonstrated that transfection of chimeric decoy ODN inhibited platelet-derived growth factor (PDGF)-induced proliferation and migration of vascular smooth muscle cells, whereas endothelial cell proliferation was not inhibited. In an in vivo study, treatment with chimeric decoy ODN significantly inhibited proximal and distal anastomotic intimal hyperplasia, and accelerated re-endothelialization. alpha-Smooth muscle actin (alpha-SMA)-positive cell proliferation was inhibited at the anastomotic sites. Expression of PDGF-BB and PDGF receptor-beta was also suppressed by chimeric decoy ODN, resulting in a reduction of alpha-SMA-positive cell accumulation. In addition, chimeric decoy ODN treatment inhibited macrophage accumulation, which was accompanied by a reduction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 gene expression. The present study demonstrates the feasibility of chimeric decoy ODN treatment for preventing neointimal formation. This strategy might be useful to improve the clinical outcome after arterial reconstruction.

Can Intimal Hyperplasia and Distal Anastomotic Intimal Hyperplasia be Controlled and Prevented?

Intimal hyperplasia (IH) and distal anastomotic intimal hyperplasia (DAIH) are ubiquitous pathologic entities encountered in vessel wall and late graft occlusion following angioplasty, stenting, endarterectomy, or bypass procedures. Flow dynamice related wall shear stress, cytokines, and growth factors are known to mediate subendothelial myoblast proliferation and matrix production, the precursor of IH development. The configuration of distal anastomosis (size mismatched end-to-end or unphysiologic end-to-side) creates oscillatory or vortex turbulent flow patterns conducive to lowand high-shear stresses as well as endothelial process lifting, particularly at the toe more than the heel of end-to-side distal anastomosis. 1 Endothelial cell damage enhances thrombocytes, leukocytes, monocytes, and blood-borne elements entering the subendothelium to promote and mediate myoblast activities leading to DAIH production. 2-3 The role of growth factors and cytokine in DAIH pathogenesis is not well defined. Transmission electron microscopic DAIH analysis of occluded/stenosed human or canine arteries revealed cell transformation and cell orientation reflective of the dynamic process in IH and DAIH pathogenesis. 4-5 IH and DAIH is composed of well-organized multi-interlamination of myoblasts and fibrocollagen matrix of 80-130 lamellar units. 6 Concurrent cell transformation (from random distribution to well-organized multi-interlamination of cell and matrix) plus cell differentiation (from mesenchyme to myofibroblasts between the graft and the lumen) coupled with the specificity of DAIH distribution (heel, toe, and floor of end-to-side distal anastomosis), and the sequence of its development have also been documented. 7-9 Active research in the past few decades has compiled a large volume of data regarding the role of cytokines and growth factor in regulating endothelial gene expression. These substances have been linked to mediating subendothelial myoblast proliferation and matrix production. The latter are ingredients needed for IH and DAIH pathogenesis. In other words, without the participation of the synthetic capacity of myoblasts and myofibroblast, IH and DAIH will not occur despite the mediation by scores of cytokines and growth factors.

Numerical Simulation of Wall Shear Stress and Particle-Based Hemodynamic Parameters in Pre-Cuffed and Streamlined End-to-Side Anastomoses

A number of research studies have related multiple hemodynamic parameters to the formation of distal anastomotic intimal hyperplasia (IH) at the sub-cellular, cellular, and tissue levels. Focusing on mitigating WSS-based parameters alone, several studies have suggested geometrically modified end-to-side anastomoses with the intent of improving synthetic graft patency rates. However, recent clinical trials of commercially available versions of these grafts indicate persistently high rates of failure. Furthermore, recent evidence suggests that platelet-wall interactions may play a significant role in the formation of IH, which is not captured by WSS-based parameters alone. In this study, numerical simulations have been conducted to assess the potential for IH formation in conventional and geometrically modified anastomoses based on both wall shear stress (WSS) conditions and platelet-wall interactions. Sites of significant particle-wall interactions, including elevated concentrations and stasis, were identified by a near-wall residence time model, which includes factors for platelet activation and surface reactivity. Conventional, pre-cuffed, and streamlined distal end-to-side anastomoses were considered with proximal and distal arterial outflow. It was found that a pre-cuffed anastomosis, similar to the Distaflo configuration, does not offer a hemodynamic advantage over the conventional design considered with respect to the magnitude of the WSS field and the potential for platelet interactions with the vessel surface. Streamlined configurations largely consistent with venous confluences resulted in an advantageous reduction of wall shear stress gradient values; however, particle-wall interactions remained significant throughout the anastomosis. Results of this study are not intended to be directly extrapolated to surgical recommendations. However, these results highlight the difficulty associated with designing an end-to-side distal anastomosis with two-way outflow that is capable of simultaneously reducing multiple hemodynamic parameters. Further testing will be necessary to determine if the observed elevated particle-wall interactions in a pre-cuffed anastomosis provide the stimulus responsible for the reported high failure rates of these grafts.

Mass Transport Disturbances in the Distal Graft/Artery Junction of a Peripheral Bypass Graft

Intimal hyperplasia (IH) development is a primary cause of failure of reconstructive bypass surgery. While the exact mechanism by which IH initiates and proliferates has yet to be fully elucidated, it is clear that the abnormal haemodynamics present in the downstream graft/artery junction are intrinsic in its development. Mass transport disturbances owing to abnormal haemodynamics have been associated with atherogenesis and it is for this reason that an investigation into transport of platelet-derived growth factor (PDGF), a known promoter of the intimal hyperplastic response, at the downstream graft/artery junction was carried out. A steady flow analysis in a three-dimensional, idealized, downstream graft/artery junction was carried out using commercial computational fluid dynamics software. It was found that there is a two-and-half fold increase in the transport of PDGF to the artery wall at the bed of the junction when compared with an idealized, healthy artery. The presence of secondary flows in the downstream arterial section also leads to large disturbances in mass transport. It was concluded that PDGF transport in the downstream graft/artery junction tends to be highly disturbed and that there may be a role of this disturbance in the initiation and subsequent development of distal anastomotic intimal hyperplasia.

Particle-hemodynamics modeling of the distal end-to-side femoral bypass: effects of graft caliber and graft-end cut

Late-stage occlusions of peripheral synthetic bypass grafts are frequently due to intimal hyperplasia and/or thrombosis at the distal anastomosis, resulting in unacceptably high failure rates. It has been widely established that hemodynamic and blood particle interactions with the vascular surface as well as surgical injury and compliance mismatch are inciting mechanisms capable of eliciting various cellular level responses associated with distal anastomotic intimal hyperplasia (IH) formation. Primary geometric factors influencing anastomotic hemodynamics include the graft-to-artery diameter ratio and graft-hood shape, which are determined by the graft caliber and initial graft-end cut selected by the vascular surgeon. In this study, the particle-hemodynamic effects of graft-end cuts (straight, curved, and S-shaped) and graft-to-artery diameter ratios (2:1 vs. 1.5:1) have been numerically assessed in four common unexpanded anastomotic configurations with respect to vortical flow patterns, wall shear stress based parameters, and platelet interactions with the vascular surface. Sites of significant platelet–wall interactions have been identified by a novel near-wall residence time (NWRT) model, which includes shear stress based factors for platelet activation and endothelial cell expression of anti-thrombogenic compounds. Of the configurations evaluated, straight and curved graft-end cuts with a graft-to-artery diameter ratio of 1.5:1 were found to reduce the particle-hemodynamic potential for IH development at locations critical to flow delivery. Nevertheless, the potential for significant IH occurrence via platelet and/or endothelial response pathways was highly evident in all conventional anastomoses considered, such that a decisively superior configuration was not determined. These results illustrate the need for alternative anastomotic designs with the intent of reducing critical hemodynamic wall parameters and mitigating regions of significant particle–wall interactions.

Numerical study of hemodynamics and wall mechanics in distal end-to-side anastomoses of bypass grafts

The development and progress of distal anastomotic intimal hyperplasia seems to be promoted by altered flow conditions and intramural stress distributions at the region of the artery–graft junction of vascular bypass configurations. From clinical observations, it is known that intimal hyperplasia preferentially occurs at outflow anastomoses of prosthetic bypass grafts. In order to gain a deeper insight into post-operative disease processes, and subsequently, to contribute to the development of improved vascular reconstructions with respect to long term patency rates, detailed studies are required. In context with in vivo experiments, this study was designed to analyze the flow dynamics and wall mechanics in anatomically correct bypass configurations related to two different surgical techniques and resulting geometries (conventional geometry and Miller-cuff). The influence of geometric conditions and of different compliance of synthetic graft, the host artery and the interposed venous cuff on the hemodynamic behavior and on the wall stresses are investigated. The flow studies apply the time-dependent, three-dimensional Navier–Stokes equations describing the motion of an incompressible Newtonian fluid. The vessel walls are described by a geometrically non-linear shell structure. In an iterative coupling procedure, the two problems are solved by means of the finite element method. The numerical results demonstrate non-physiological flow patterns in the anastomotic region. Strongly skewed axial velocity profiles and high secondary velocities occur downstream the artery–graft junction. On the artery floor opposite the junction, flow separation and zones of recirculation are found. The wall mechanical studies show that increased compliance mismatch leads to increased intramural stresses, and thus, may have a proliferative influence on suture line hyperplasia, as it is observed in the in vivo study.

Apolipoprotein J inhibits the migration, adhesion, and proliferation of vascular smooth muscle cells

Purpose: Apolipoprotein J (ApoJ) is expressed during tissue injury and remodeling and has been implicated in vascular smooth muscle cell (VSMC) differentiation. Recently, the gene for ApoJ was identified as upregulated in distal anastomotic intimal hyperplasia after prosthetic arterial grafting. In this study we investigate the effect of ApoJ on VSMC migration, adhesion, proliferation, and gene expression. Methods: To study the effect of ApoJ on cell migration, we used a microchemotaxis chamber with an intervening 8-μm pore semipermeable polycarbonate membrane. Assays were performed with ApoJ alone (1-50 μg/mL) or in combination with platelet-derived growth factor homodimer bb (PDGF-bb; 10 ng/mL) or 2% fetal bovine serum (FBS; n = 8) in the lower wells. The influence of extracellular matrix interactions on ApoJ and chemotaxis was studied in a similar way, except membranes were collagen coated. Furthermore, cells were exposed to ApoJ 15 minutes before or after seeding on the coated membrane (n = 10). The influence of ApoJ on cell adhesion to collagen was assessed with cell exposure to ApoJ 15 minutes before or after seeding on a collagen-coated membrane (n = 10). Migration and adhesion were quantified by counting the number of cells per three independent high-power fields with light microscopy. The effect of ApoJ in 0.4% FBS with or without PDGF-bb on VSMC proliferation (n = 12) was assessed by means of [Methyl-3H] thymidine incorporation. The transcriptional profile of VSMCs in 2% FBS exposed to ApoJ and a control for 24 hours was analyzed with an oligonucleotide microarray containing 12,560 genes. Results: ApoJ alone was not chemotactic for VSMCs. Without collagen, ApoJ decreased the migration of VSMCs toward 2% FBS by 96% or more starting at 10 μg/mL (P <.05) and toward PDGF-bb by 60.9% or more starting at 25 μg/mL (P <.05) compared with the control. When collagen was introduced, ApoJ (25 μg/mL) decreased migration toward 2% FBS by 64% (P <.01) and toward PDGF-bb by 67.5% (P <.01) and decreased adhesion by 26.8% (P <.01) only when VSMCs in solution were exposed to ApoJ before placement on collagen. ApoJ did not induce VSMC proliferation. ApoJ alone decreased VSMC thymidine incorporation by 41.1% at 25 μg/mL (P <.05). ApoJ decreased thymidine incorporation of PDGF-bb stimulated VSMCs by 42.8% at 50 μg/mL (P <.05). Interleukin-8 and endothelin-1 were demonstrated by means of the microarray to be differentially expressed more than twofold in VSMCs that were exposed to ApoJ. Conclusion: ApoJ is a potent inhibitor of VSMC migration, adhesion, and proliferation. Its genetic targets are linked to cell senescence and differentiation. Therefore, ApoJ may play a role, in part, in modulating the VSMC response to injury. (J Vasc Surg 2001;34:716-23.)

The Effect of Proximal Artery Flow on the Hemodynamics at the Distal Anastomosis of a Vascular Bypass Graft: Computational Study

The formation of distal anastomotic intimal hyperplasia (IH), one common mode of bypass graft failure, has been shown to occur in the areas of disturbed flow particular to this site. The nature of theflow in the segment of artery proximal to the distal anastomosis varies from case to case depending on the clinical situation presented. A partial stenosis of a bypassed arterial segment may allow residual prograde flow through the proximal artery entering the distal anastomosis of the graft. A complete stenosis may allow for zero flow in the proximal artery segment or retrograde flow due to the presence of small collateral vessels upstream. Although a number of investigations on the hemodynamics at the distal anastomosis of an end-to-side bypass graft have been conducted, there has not been a uniform treatment of the proximal artery flow condition. As a result, direct comparison of results from study to study may not be appropriate. The purpose of this work was to perform a three-dimensional computational investigation to study the effect of the proximal artery flow condition (i.e., prograde, zero, and retrograde flow) on the hemodynamics at the distal end-to-side anastomosis. We used the finite volume method to solve the full Navier-Stokes equations for steady flow through an idealized geometry of the distal anastomosis. We calculated the flow field and local wall shear stress (WSS) and WSS gradient (WSSG) everywhere in the domain. We also calculated the severity parameter (SP), a quantification of hemodynamic variation, at the anastomosis. Our model showed a marked difference in both the magnitude and spatial distribution of WSS and WSSG. For example, the maximum WSS magnitude on the floor of the artery proximal to the anastomosis for the prograde and zero flow cases is 1.8 and 3.9 dynes/cm2, respectively, while it is increased to 10.3 dynes/cm2 in the retrograde flow case. Similarly, the maximum value of WSSG magnitude on thefloor of the artery proximal to the anastomosis for the prograde flow case is 4.9 dynes/cm3, while it is increased to 13.6 and 24.2 dynes/cm3, respectively, in the zero and retrograde flow cases. The value of SP is highest for the retrograde flow case (13.7 dynes/cm3) and 8.1 and 12.1 percent lower than this for the prograde (12.6 dynes/cm3) and zero (12.0 dynes/cm3) flow cases, respectively. Our model results suggest that the flow condition in the proximal artery is an important determinant of the hemodynamics at the distal anastomosis of end-to-side vascular bypass grafts. Because hemodynamic forces affect the response of vascular endothelial cells, the flow situation in the proximal artery may affect IH formation and, therefore, long-term graft patency. Since surgeons have some control over the flow condition in the proximal artery, results from this study could help determine which flow condition is clinically optimal.

Blood Flow in Distal End-to-side Anastomoses with PTFE and a Venous Patch: Results of an In vitro Flow Visualisation Study

Objectives: non-physiological flow behaviour plays a significant role in the development of distal anastomotic intimal hyperplasia. To investigate flow patterns in four anastomotic types of femoral end-to-side distal bypass graft anastomoses, a flow visualisation study was performed. Methods: transparent 1:1 casted replicas of distal vascular graft anastomoses created by conventional technique, Miller-cuff, Taylor- and Linton-patch were fabricated. A pulsatile mock circulation with a high-speed video system was constructed. Flow pattern was determined at mean Reynolds numbers 100–500. Migrations of the stagnation points on the bottom of the anastomoses at mean Reynolds numbers 100, 230, and 350 were measured.Results : a vortex forms during early systole and increases to maximum systole in all anastomoses. During the diastolic phase the vortex moves in the Miller-cuff distally to the toe of the anastomosis and remains standing, while in the other anastomotic types the vortex moves proximally to the heal of the junction and breaks down. The shift of the stagnation point in the Miller-cuff was considerably smaller than in the other anastomoses. Conclusion: conventional, Linton and Taylor anastomoses show similar flow patterns. The Miller-cuff with its wider cavity shows lower shift of the bottom stagnation point, but a persistent washout of the anastomotic cavity, which may contribute to its reported good clinical performance.

Evaluation of Distal Anastomotic Intimal Hyperplasia: An Experimental Comparison by Arteriography, Duplex Sonography, Angioscopy, and Intravascular Ultrasound

Routine follow-up investigation methods after peripheral arterial bypass surgery, such as arteriography and colour duplex sonography, do not always allow correct analysis of moderate alterations in the vessel wall, e.g. initial stages of distal anastomotic intimal hyperplasia (DAIH). The aim of this study was to evaluate the efficiency of angioscopy and intravascular ultrasound compared to the named routine methods regarding detection of early DAIH. Eight months after bilateral femoropopliteal bypass surgery with venous grafts in 18 sheep, we investigated the distal anastomotic sites using the named methods. The findings were then correlated to histologic specimens. Intravascular ultrasound presented the highest sensitivity followed by angioscopy, with results markedly different from the findings arrived at by conventional methods.

Distal Anastomotic Intimal Hyperplasia: Histocytomorphology, Pathophysiology, Etiology, and Prevention

The ubiquitous relationship of late graft occlusion, particularly the nonautogenous bypasses and distal anastomotic intimal hyperplasia (DAIH), has been extensively investigated. After having established the specific location of DAIH in human autogenous, biologic and prosthetic late graft occlusion, canine models were designed to elucidate the role of compliance mismatch between graft and the host artery and the configuration of the distal end to side versus end to end anastomosis using autogenous artery. DAIH occurred in all end to side anastomosis but not in side matching end to end anastomosis. Compliance mismatched is not the cause of DAIH development, but it enhances the pathogenesis. Further study using pharmacologic agents to modulate the activities of vascular myoblasts was successful in attenuating DAIH development and progression. Since DAIH occurs through a cascade of events initiated by endothelial lifting of the overlapping processes at the gap junction to allow blood borne elements to enter the subendothelial space, then incites myoblast proliferation and matrix synthesis leading to DAIH formation at the heel and toe where oscillatory flow exists. Control of myoblast activity is needed on a permanent basis to prevent DAIH development and progression. Cessation of treatment allows resurgence of DAIH biogenesis. Direct regulation of vascular myoblast activity preclude the need of inhibiting other source of stimuli that increases as our knowledge of the subject grows. Without the participation of myoblast, there will be no DAIH irrespective of the potency and numbers of enzymatic, hormonal, or mechanical inciting factors.

Flow waveform effects on end-to-side anastomotic flow patterns

Purpose: Restenosis due to distal anastomotic intimal hyperplasia, a leading cause of arterial bypass graft failure, is thought to be promoted by hemodynamic effects, specifically ‘abnormal’ wall shear stress patterns. The purpose of this study was to quantify the effects of flow waveform on peri-anastomotic flow and wall shear stress patterns. Methods: Blood flow and wall shear stress patterns were numerically computed in a representative three-dimensional anastomosis using femoral, iliac and coronary flow waveforms suitable for humans at rest. Numerical results were validated against experimental data. Results: Peri-anastomotic wall shear stress patterns were influenced by a complex interplay between secondary flow effects and unsteadiness. Peripheral flow waveforms (iliac, femoral) produced large temporal and spatial wall shear stress gradients on the host artery bed. In comparison, the coronary flow waveform produced normalized bed wall shear stress gradients that were a factor of 2–3 less than for the peripheral waveforms, even though average bed wall shear stress magnitudes were similar for the two waveforms. Conclusions: If anastomotic intimal hyperplasia is promoted by large spatial and/or temporal gradients of wall shear stress, as has been proposed, this study predicts that there will be markedly less intimal hyperplasia on the host artery bed of coronary bypass grafts than for peripheral bypass grafts. This information, in conjunction with a comparative histopathologic study of intimal hyperplasia distribution, could help determine specific wall shear stress factors promoting intimal hyperplasia.

Compliance mismatch may promote graft–artery intimal hyperplasia by altering suture-line stresses

The role of graft-artery compliance mismatch in the development of distal anastomotic intimal hyperplasia (DAIH) is not yet resolved. Although DAIH develops at all surgically created anastomoses, increased compliance mismatch does not lead to greater hyperplasia formation in end-to-end anastomoses, but in end-to-side anastomoses, it leads to a profound increase in hyperplasia. The current study was undertaken to determine whether suture-induced anastomotic stresses could explain these findings. A large strain finite element analysis of vascular wall mechanics was performed to compare the influence of compliance mismatch on intramural stresses in end-to-end versus end-to-side anastomoses. A novel modelling approach was implemented which includes suture-induced stress concentrations. End-to-end and end-to-side graft-artery simulations were executed using (1) artery (compliance= C=0.44% kPa -1), (2) vein ( C=0.33% kPa -1), and (3) Dacron ( C=0.14% kPa -1) grafts. Residual stresses due to axial tension were included and the anastomoses were statically inflated to 13.3 kPa (100 mmHg). Elevated intramural stresses were found to exist at both the end-to-end and end-to-side graft–artery junctions; however, in the end-to-end anastomosis, the maximum anastomotic stress was not a function of the graft compliance, whereas in the end-to-side anastomosis, the maximum stress was a strong function of graft compliance. For the 45° end-to-side geometry considered in this study, the maximum anastomotic stress concentration obtained using a stiff Dacron graft was more than 40% greater than that obtained using a compliant artery graft. In the end-to-end anastomosis, the Dacron graft led to a less than 5% increase in maximum stress over the artery graft. Therefore, increased compliance mismatch increases stresses and promotes DAIH in end-to-side junctions, but, it has little influence on either stresses or DAIH in end-to-end junctions. Thus, the proliferative influence of increased compliance mismatch on suture-line hyperplasia in end-to-side anastomoses can be explained by the resulting increase in intramural stresses. In addition, since high stresses were found in both geometries, elevated suture-line intramural stresses may be an important proliferative stimulus for intimal hyperplasia formation in all vascular reconstructions.

Numerical study of wall mechanics and fluid dynamics in end-to-side anastomoses and correlation to intimal hyperplasia

In order to analyse the wall mechanics and the flow dynamics in compliant vascular distal end-to-side anastomoses, computer simulation has been performed. In a model study the effect of compliance mismatch on the wall displacements and on the intramural stresses as well as the influence of wall distensibility on the flow patterns are demonstrated applying two distensible models with different graft elasticity. In addition, the flow in a rigid model simulating a vein graft without adaption of the venous lumen has been investigated. The geometries for these models were obtained from a concurrent experimental study, where the formation of distal anastomotic intimal hyperplasia (DAIH) was studied in untreated and externally stiffened autologous venous grafts in sheep. In the flow study the time-dependent, three-dimensional Navier-Stokes equations describing the motion of an incompressible Newtonian fluid are applied. The vessel wall is modelled using a geometrically non-linear shell structure. In an iteratively coupled approach the transient shell equations and the governing fluid equations are solved numerically using the finite element method. In both compliant models maximum displacement and areas of steep stress gradients are observed in the junction region along the graft-artery intersection. The comparison of the normal deformations and the distribution and magnitude of intramural stress shows quantitative differences. The graft elasticity acts as a regulating factor for the deformability and the stress concentration in the junction area: In the model with high graft-elasticity maximum normal deformation at the side wall is 17%. This is twice as large as in the stiff graft model and maximum principle stress at the inner surface differs by one order of magnitude. The numerical results concerning the flow patterns indicate strongly skewed axial velocity profiles downstream of the junction, large secondary motion, flow separation and recirculation on the artery floor opposite the junction and at the inner wall downstream of the toe. In these regions a correlation between the time-averaged fluid wall shear stress and intimal thickening found in the animal experiment can be observed, whereas the pronounced formation of DAIH at the suture line seems to be mainly dependent on wall mechanical factors such as intramural stress and strain.

Compliance mismatch and formation of distal anastomotic intimal hyperplasia in externally stiffened and lumen-adapted venous grafts

Compliance and formation of distal anastomotic intimal hyperplasia (DAIH) were investigated in externally stiffened venous grafts of varying calibers. 36 femoropopliteal reconstructions were performed in 18 sheep. The autologous venous grafts were inserted into tubes made of Dacron mesh to achieve compliance-mismatch and lumen adaptation. Compliance was measured by echotracked ultrasonography and profiles of DAIH were generated from histologic sections harvested after 8.3 months. The external mesh tube significantly lowered the local compliance of graft and host artery. DAIH appeared extensively in those groups where mesh tube constricted venous grafts met untreated host arteries (p = 0.002). No differences in compliance and DAIH formation were observed when grafts with large and adapted diameters were compared. For prevention of DAIH the distal venous graft diameter is not important, while the local compliance of an autologous vein is a predictive factor for DAIH formation and thus long-term patency.

Compliance and Formation of Distal Anastomotic Intimal Hyperplasia in Dacron Mesh Tube Constricted Veins Used as Arterial Bypass Grafts

Dilated and varicose veins constricted with a Dacron mesh tube were successfully used as arterial bypass grafts to avoid nonautogenous vascular prostheses. Mesh constriction has also been used to adapt the venous graft lumen to the diameters of grafted arteries. The influence of the external mesh on the wall elasticity of such venous grafts and the reactions of the host artery were not investigated. Elastic properties of mesh constricted autologous veins used as arterial grafts in femoropopliteal reconstructions, as well as consecutive formation of distal anastomotic intimal hyperplasia (DAIH), were investigated in this experiment. Twenty-four autologous venous grafts were implanted in 12 sheep. Grafts were left natural (Groups 1 and 3) or were constricted with an external Dacron mesh (Groups 2 and 4); their diameters were left unchanged (Groups 1 and 2) or were matched to the diameter of the host artery (Groups 3 and 4). Wall elasticity of the graft, distal anastomosis, and distal artery were measured by locally applied crystal transducers during surgery and follow-up. Formation and localization of DAIH was evaluated histomorphologically after a median of 8.3 months. Graft wall elasticity was found to be lower (54.6 vs. 147.9, P = 0.006) and overall DAIH was found to be higher in mesh tube grafts (49.42 vs. 20.8 microns, P = 0.001, Mann-Whitney U-test). No differences in elasticity and DAIH formation were observed between grafts with adapted and large diameters. Constriction of venous grafts by a Dacron mesh tube reduces graft wall elasticity and promotes formation of DAIH. To avoid such an increased mismatch in compliance while making use of the advantages of this method, the external mesh tube must not be brought close to the distal anastomotic area itself.

A Numerical Simulation of Flow in a Two-Dimensional End-to-Side Anastomosis Model

In order to understand the possible role that hemodynamic factors may play in the pathogenesis of distal anastomotic intimal hyperplasia, we carried out numerical simulations of the flow field within a two-dimensional 45 degree rigid-walled end-to-side model anastomosis. The numerical code was tested and compared with experimental (photochromic dye tracer) studies using steady and near-sinusoidal waveforms, and agreement was generally very good. Using a normal human superficial femoral artery waveform, numerical simulations indicated elevated instantaneous wall shear stress magnitudes at the toe and heel of the graft-host junction and along the host artery bed. These sites also experienced highly variable wall shear stress behavior over the cardiac cycle, as well as elevated spatial gradients of wall shear stress. These observations provide additional evidence that intimal hyperplasia may be correlated to wall shear stresses over the cardiac cycle, high wall shear stress gradients, or a combination of the three. The limitations of the present work (especially in regard to the two-dimensional nature of the flow simulations) are discussed, and results are compared to previous observations about distal anastomotic intimal hyperplasia.