PROJECT REPORT

EFFECT OF THE ANASTOMOTIC ANGLE IN ARTERIOVE-NOUS FISTULA ON THE INDUCED HEMODYNAMICS

Submitted ToThe 2012- 2013 Academic Year NSF REU Program

Part ofNSF Type 1 STEP Grant

Sponsored ByThe National Science Foundation

Grant ID No.: 0756921

College of Engineering and Applied ScienceUniversity of Cincinnati

Cincinnati, Ohio

Prepared By:Briana Conners, Chemical Engineering, University of Cincinnati

Kenechukwu Okoye, Biomedical Engineering, University of Cincinnati

Report Reviewed By:

______________________________

Rupak K. Banerjee, PhD

ProfessorSchool of Dynamic Systems

College of Engineering and Applied ScienceUniversity of Cincinnati

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 Abstract

Arteriovenous fistulae (AVFs) are the preferred form of the vascular access for hemodialysis; however, 50% fail to mature and reach adequate diameter and flow rate constraints to support dialysis [1].  Hemodynamic parameters, specifically wall shear stress (WSS), are believed to play a crucial role in the maturation or failure of AVFs. Our goal is to study the effects of the configuration of AVF on the correspond-ing hemodynamic parameters.  Based on our previous experimental data on an in-vivo porcine model, a computerized AVF model with a 90° anastomotic angle and one with a 60° anastomotic angle were created. The hemodynamic parameters within each AVF were then obtained using numerical techniques under steady state condition.  In both AVFs, recirculation zones formed along the inner bends of the curved segment of the vein resulting in negative axial WSS in those locations.  This zone was larger for the 60° AVF as it was extended to the straight segment of the outflow vein, while it was limited to the curved region in the 90° case. The 60° AVF had the greatest magnitude of negative WSS (= -130.19 dyne/cm2) on the inner bend relative to the 90° case (= -55.16 dyne/cm2).  Additionally, the highest positive axial WSS was found on the side wall of the 60° AVF (= 354.33 dyne/cm2) as com-pared to the 90° case (= 342.76 dyne/cm2).  Thus, the 90° AVF with less reversed flow along the inner bend and lower potentially damaging high WSS on the outer wall seems to have more advantageous hemodynamic parameters. Substantial vari-ation in the flow profiles with anastomotic angle shows that the surgical configura-tion of an AVF has a considerable effect on its hemodynamics and thus the eventual maturation or failure of the access.  Consequently, proper attention to this very im-portant factor can have a significant effect on the dialysis patients’ health care.    

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Acknowledgements

Rupak K. Banerjee, PhD Dr. Banerjee has been a main source of support throughout the project. We're thankful as a team that Dr. Banerjee has made himself available for our project, always submitting his ideas and offering assistance where needed. His expertise and experience have proved valu-able for the project as a whole.

Ehsan Rajabi JagharghWe couldn't have asked for more when it comes to a graduate assistant. Ehsan has not only volunteered his time for the sake of this project, but went far above and beyond his duties as Graduate Assistant. He put countless hours towards some of the most crucial aspects of the project and we honestly cannot thank him enough. As rewarding as it is to see the project near its completion, we know that it would not have been at all possible without Ehsan’s hard work.

Urmila Ghia, PhDAnant Kukreti, PhDKristen Strominger

Special thanks to:Ted BaldwinCurtis FoxKarman Ghia, PhDDottie StoverDaria Narmoneva, PhDKelly Cohen, PhDLilit Yeghiazarian, PhDMargaret Kupferle, PhDDharma Agrawal, PhDMark Turner, PhDHeng Wei, PhDNoe Alvarez, PhD

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Introduction Hemodialysis is the most common treatment for patients with end stage renal diseases (ESRD). Hemodialysis access is made by the surgical connection of a vein to an artery. The permanent dialysis access has two major forms which are arteri-ovenous fistula (AVF) and arteriovenous graft (AVG). Among these two forms, AVFs are the preferred mode for dialysis because of their relatively longer survival rate and fewer complications. In order to be successful and considered mature, an AVF must reach certain constraints on flow rate, diameter, and time. Unfortunately, a significant number of AVFs (28 to 53%) fail to mature adequately to support dialysis therapy [1]. Currently, one of the most important reasons for an AVF to fail to ma-ture is venous stenosis due to accelerated venous neointimal hyperplasia (NH) [2]. Venous stenosis has been found in 65-100% of angiographically evaluated failing AVFs and is located either in the vein immediately downstream of the anastomosis or within the anastomosis itself in more than half of the AVFs [1].

While the exact pathway of the neointimal hyperplasia is unknown, previous studies have demonstrated that hemodynamics, principally wall shear stresses (WSS), play an important role in the formation, localization, and development of neointimal hyperplasia. The NH has been correlated to regions of low or oscillating wall shear stress in which endothelial cells cannot align in the direction of the flow and smooth muscle cells in the neointima appear disoriented when examined [3]. These areas of low WSS were particularly likely to occur at the arteriovenous anas-tomosis. Excessively high WSS, which exists in AVFs due to multi-fold increase in ve-nous flow rate, can also damage endothelial cells and activate platelets that lead to NH [2].

Prior studies showed that anatomical configuration of AVF plays a major role in flow-mediated dilation. Specifically, previous studies on in-vivo porcine models have shown that the different configurations of AVF can have a significant effect on the venous flow rate and diameter over time [2]. Also, the effects of geometrical parameters, mainly the anastomotic angle, on the flow patterns and distribution of WSS within the idealized AVF configuration were studied. It was shown that zones of low and oscillatory shear stress were located in the same sites in which growing intima-media thickness and successive stenosis development were documented. However, in these idealized geometries, proximal and distal arteries were assumed to have the same diameter which does not hold true in most clinical cases [2]. In addition, in the recent study by Ene-Iordache et al. [3], the diameter of outflow vein was also assumed to be the same as that of the proximal and distal arteries, which is far from reality. Therefore, there is a need to study the geometrical effects in a more practical setting. In this study, the geometrical characteristics of the model were chosen from our previous experimental data on a porcine model [1]. Our goal is to study the effect of anastomotic angle on the hemodynamic parameters in AVFs. We believe that the knowledge on the geometrically induced hemodynamics in AVFs can be beneficial to the health care of hemodialysis patients.

Methods

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The schematic of the AVF’s geometry is shown in Figure 1. Two AVFs were con-sidered in our analysis with 60° and 90° anastomotic angles. Dimensions of the proximal, distal, and outflow vein were chosen based on our in-vivo experimental data in a porcine model [1]. An unstructured grid was generated for each AVF. The numerical domain was solved using control volume techniques to obtain the flow field within each AVF under steady state condition. Velocity boundary conditions were applied at the proximal and distal arteries, and an outflow condition was speci-fied at the outflow vein. The flow rates at the proximal and distal arteries were also chosen based on our in-vivo porcine experiments [1] with corresponding Reynolds numbers of 1464 and 508, respectively. In the result section, the axial velocity pro-files were shown at two cross-sections located at middle bend and end of the bend in the symmetry plane of AVF. These two cross-sections are denoted by sections 1 and 2 in Figure 1. Moreover, the outer, side, and inner walls of the bend segment along which the distribution of WSS is shown are specified in Figure 1.

Figure 1. Schematic of the AVF model. The connection of the outflow vein to the artery at an angle, theta, was varied to create two models. The dimensional values and flow parameters used for the model were empirically determined from the pre-vious porcine in-vivo experiments [1].

Results Effect of Configuration on the Flow Field of AVFs. The effects of different anas-tomotic angles on the hemodynamics of the AVFs were studied by comparing the flow pathlines and velocity field within the 60° and 90° AVFs. Figure 2 shows the three-dimensional pathlines of the particles that were released from the inlet of the proximal artery and left the domain through the outflow vein. These pathlines are colored by the velocity magnitude. Both 60° and 90° AVFs depicted a region of re-circulating flow inside of the curved portion of the access. The velocity contours along the symmetry plane for both the 90° and 60° cases are shown in Figure 3. In both cases, the high velocity region was shifted towards the outer wall of the bend, while the particles with lower momentum were located at the inner wall of the bend. The particles with lower velocity magnitude separated from the wall and formed the recirculation zones along the inner wall of the bend. As the flow advanced towards the straight segment of the outflow vein, velocity field started oscillating which re-sulted in shedding of vortices that were formed inside the bend and washed away by the main flow. This phenomenon can be noticed by the formation of multiple high velocity packets along the outer wall (Figure 3; regions specified by “*”) as well as the swirling patterns of the pathlines (Figure 2; regions specified by “*”).

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Figure 2. Flow pathlines colored by the velocity magnitude for the 90° and 60° AVFs.

Figure 3. Velocity contours at the symmetry plane of the AVFs. Here, velocity mag-nitude is shown.

The axial velocity profiles in the two specified cross-sections (Figure 1) on the symmetry plane of the AVFs are compared between the two cases as shown in Fig-ures 4A and 4B. These profiles were plotted along the non-dimensional radial dis-tance from the inner bend to the outer bend of the model. The axial velocity pro-files in Section 1 followed a similar pattern (Figure 4A) for both 90° and 60° AVFs. The axial flow was initially negative, indicating backward flow, and then began to have positive values after the center of the vessel. Moving towards the outer wall, the axial velocity increased and formed the maximum velocity packets along this wall. This phenomenon can be associated with the formation of dean vortices in the bend (not shown here) which pushed the maximum velocity point towards the outer wall. Despite the similar patterns of the axial velocity profiles, the magnitudes of the maximum forward (60°: 1.60 m/s vs. 90°: 1.28 m/s) and maximum backward (60°: -0.55 m/s vs. 90°: -0.27 m/s) axial velocities were both greater for the 60° case. Section 2 was marked by flow with lower velocity on the inner wall and maxi-mum velocity along the outer wall. For the 90° case, axial velocity was positive along the entire section, however, some negative flow was observed along the inner wall of the 60° AVF. This later shows that the recirculation zone was larger for the 60° case as it extended to the straight segment of the outflow vein.

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60 AVF90 AVF

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Figure 4. Axial velocity profiles versus normalized radial distance from the inner to the outer wall for (A) section 1 and (B) section 2.

Effect of Configuration on the WSS Distribution in AVFs. WSS is another impor-tant flow parameter as it is directly sensed by the endothelial cells and is believed to be the main actuator of flow-mediated remodeling in AVFs. The contour plots of WSS magnitude for both 60° and 90° AVFs are shown in Figure 5. WSS is high in the anastomotic junction, outer and side walls of the bend when compared to the relatively lower levels of WSS along the inner wall. The high levels of WSS along the outer and side walls of the bend can be attributed to the existence of the maximum velocity around this wall, while the low WSS levels along the inner wall of the bend can be associated with the lower magnitude of velocity at this region.

Figure 5. WSS contours along the AVFs with 90 and 60 anastomotic angles.

Axial WSS is plotted along the outer, inner, and side walls of the bend segment for both 90° and 60° cases in Figures 6A and 6B, respectively. The axial WSS varia-tion is plotted along the sweep angle of the each bend. For both cases, axial WSS values along the outer and side walls are positive whereas they are negative on the inner wall. In the 90° case (Figure 6A) the average axial WSS on the outer and side walls were 307.15 and 342.76 dyne/cm2, respectively, while they were 297.12 and 354.33 dyne/cm2 for the 60° case (Figure 9B), respectively. For the 60° case as compared to the 90° AVF, the WSS profile along the inner wall of the bend showed more negative values, indicating a higher flow in the backwards direction. More-over, in the 90° case axial WSS values eventually met positive levels, indicating flow returning to direction of the flow, whereas for the 60° AVF flow continued to ex-ert negative axial WSS values even at the end of the anastomosis. The average ax-ial WSS along the inner wall of the bend was -55.16 dyne/cm2 for the 90° AVF, while it was almost doubled for the 60° case (-130.19 dyne/cm2).

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Figure 6. Axial wall shear stress variation as a function of the sweep angle of the bends for (A) 90° and (B) 60° AVFs.

Discussion From this initial output, the differences in the flow profiles between the two AVFs were evident. In both cases, areas of recirculation and stagnant flow were formed on the inner wall of the bend segment. It has been established that this type of flow is detrimental to the AVF’s ability to mature. Between the two cases, the anastomosis that created a 90° angle between the proximal artery and the con-necting outflow vein was characterized by less pronounced recirculative flow in the inner portion of the curve. In addition, though abnormally low values of WSS have been linked to the development of neointimal hyperplasia, WSS levels that are too far in excess of normal physiological values may also be detrimental to the success of fistula maturation. This suggests that the 60° AVF with higher WSS on the side walls when compared to the 90° case may be more prone to the maturation failure problem.

Although the results showed the effects of configuration on the hemodynamics patterns of AVFs, the analysis was based on a simplified model and thus, could not represent a clinical case. Nonetheless, these models can provide important insight into the factors that determine the vascular remodeling needed for hemodialysis. Other anastomotic angles can also be analyzed to confirm the trends in hemody-namic parameters identified in this study.

Conclusion AVFs with a 60° and a 90° anastomotic angle were studied. Although the veloc-ity patterns and WSS distribution in the two cases followed similar general trends, WSS levels and the length and strength of the recirculation zones differed. These differences can increase the possibility of future complications such as venous stenosis in one case as compared to the other. Therefore, our results suggest that

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such studies on the geometrical effects of AVFs are needed for improving the pa-tency rate and patient care in the hemodialysis population.

References

1. Krishnamoorthy, M. K. et al., 2012, “Anatomic configuration affects the flow rate and diameter of porcine arteriovenous fistulae.” Kidney International, 81, pp. 745-750.

2. Krishnamoorthy, M. K. et al., 2008, “Hemodynamic wall shear stress profiles influence the mag-nitude and pattern of stenosis in a pig AV fistula.” Kidney International, 74, pp. 1410-1419.

3. Ene-Iordache, B. et al., 2011, “Disturbed flow in radial-cephalic arteriovenous fistulae for haemodialysis: low and oscillating shear stress locates the sites of stenosis.” Nephrol Dial Trans-plant, 27, pp. 358-368.

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