Session: 17-01-01: Research Posters

Paper Number: 149318

149318 - Retrograde Flow in Mouse Arteriovenous Fistula 

Background: The arteriovenous fistula (AVF), created by direct anastomosis of an artery and nearby vein, is the lifeline for patients on maintenance hemodialysis. However, AVF have high failure rates due to insufficient increases in lumen diameter and flow of the venous limb needed for dialysis. Hemodynamics have long thought to play a part in AVF remodeling; consequently, computational methods such as computational fluid dynamics (CFD) are commonly used to investigate AVF flow and its association of AVF remodeling. Rarely studied thus far is retrograde flow (RF) in the distal artery of the AVF, despite its associations with conditions such as steal syndrome in humans. The endothelial nitric oxide synthase (NOS3) generates a potent vasodilator (i.e., nitric oxide) that we have previously shown to improve AVF outcomes, including limited neointimal hyperplasia, expanded venous lumen, smoother velocity streamlines, and hemodynamics trending toward baseline levels. However, RF analysis in mouse AVFs has not been reported. Here we present a novel MRI-based CFD study analyzing RF in genetically modified mice with AVF.

Methods: Carotid-jugular AVF were created in C57BL/6 mice with three conditions: NOS3 overexpression, NOS3 knockout, and wild-type control. Magnetic resonance imaging of AVF were performed 7 and 21 days after AVF creation for each strain (n=3-6/group, total 25 mice) and used for AVF lumen reconstruction, velocity extraction (i.e., MRI-measured velocity) and CFD. CFD was performed with velocity boundary conditions at the proximal vein and artery, and pressure boundary condition at the distal artery, thus allowing for flow reversal at this location. Percent RF throughout a cardiac cycle in the distal artery was extracted from both MRI images (which occurred ~ 1.5  +/- 0.6 mm away from the anastomosis) and CFD derived analysis at the same location. CFD derived volumetric venous flow rate and AVF venous diameter in AVF lumen reconstruction were taken from 5 mm away from the anastomosis.

Results: All 25 mice had RF at least partially throughout the cardiac cycle in both MRI and CFD extracted velocity. MRI-measured velocity showed that 1 mouse had less than 20% RF, 12 had 21-69%, 7 had 70-99%, and 5 had 100% RF, with no association between distal artery RF and venous flow rate, venous diameter, NOS3 condition, or time point. CFD derived velocity showed that 1 mouse had less than 20% RF, 2 had 21-69%, 7 had 70-99% RF and 15 had 100% RF. CFD derived distal artery RF was correlated with venous flow rate (r=0.4612, p=0.0203) but not venous diameter, NOS3 condition, or time point.

Conclusion: Retrograde flow in the distal artery is present and prevalent in mouse carotid-jugular AVF models. Consequently, mouse models may be a translational model for studying steal syndrome. However, surprisingly the presence of RF is the same in all three NOS3 strains even though they have different AVF outcomes.

Presenting Author: Hannah Northrup University of Utah

Presenting Author Biography: Hannah has a PhD and Masters in Biomedical Engineering and Bachelors in Biochemistry. She is currently working remotely as Postdoctoral Research Associate for the University of Utah. Her current research is focused on computational models of arteriovenous fistula.

Authors:

Hannah Northrup University of Utah
Timmy Lee University of Alabama at Birmingham
Yan-Ting Shiu University of Utah