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Abstract: SA-PO012

Effect of Endothelial Nitric Oxide Synthase Expression Levels on the Hemodynamic Parameters in Murine Arteriovenous Fistulas

Session Information

  • Bioengineering
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Baltazar, Shelly R., The University of Utah, Salt Lake City, Utah, United States
  • Fairbourn, Brayden, The University of Utah, Salt Lake City, Utah, United States
  • Northrup, Hannah M., The University of Utah, Salt Lake City, Utah, United States
  • Lee, Timmy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Shiu, Yan-Ting Elizabeth, The University of Utah, Salt Lake City, Utah, United States
Background

The arteriovenous fistula (AVF) is the preferred hemodialysis vascular access but has a high maturation failure rate, which is a significant clinical problem. The creation of AVFs causes aberrant blood flow at and near the AVF anastomosis that may cause maturation failure. Endothelial nitric oxide synthase (NOS3) generates nitric oxide (NO), a vasodilator. Our group previously reported that NOS3 expression levels affect AVF development (i.e., lumen size) in a mouse model. Specifically, the AVF lumen in NOS3 overexpression (OE) was larger (favored AVF remodeling) than in NOS3 knock out (KO) or wild type (WT) mice at Day 7 and Day 21 post AVF creation (Kidney360, 1(9): 925, 2020). In this study, we performed MRI-based computational fluid dynamics (CFD) simulations in a similar model. We hypothesized that blood flow in OE is less aberrant than that in KO and WT.

Methods

Carotid-jugular AVFs were created in C57BL/6 mice with three conditions: NOS3 OE, NOS3 KO, and WT control. MR images of AVFs were taken on Day 7 and Day 21 post AVF creation for each strain (n=2-3 per condition, 17 mice total) and used for CFD simulations to quantify the wall shear stress (WSS) and vorticity of the AVF vein. The WSS and vorticity were averaged over the third cardiac cycle and 5 mm from the anastomosis through the AVF vein.

Results

On Day 7, the WSS (67.56 ± 137.9 dyn/cm2 for OE, 120.0 ± 241.3 dyn/cm2 for KO, 104.1 ± 181.0 dyn/cm2 for WT) and vorticity (1146 ± 1827 1/s for OE, 1739 ± 2766 1/s for KO, 1608 ± 2506 1/s for WT) were not statistically different among the three groups. On Day 21, OE had lower WSS (13.67 ± 16.17 dyn/cm2) and vorticity (190.7 ± 246.6 1/s) than KO (100.6 ± 169.3 dyn/cm2; 1893 ± 2804 1/s) and WT (165.8 ± 267.1 dyn/cm2; 2244 ± 3045 1/s) (p<0.0001).

Conclusion

At Day 21, lower vorticity in OE suggested that the velocity streamlines in OE were smoother than in KO and WT, and lower WSS in OE suggested that WSS was attempting to return to the pre-surgery baseline. Both are characteristics of favored hemodynamics remodeling. We are continuing to refine CFD protocols and increase animal numbers for future studies.

Funding

  • NIDDK Support