11/8/2022 0 Comments Slice tecplot 2018Inward remodeling results from the formation of neointimal hyperplasia to decrease the open lumen area. Outward remodeling results from the relaxation of vascular smooth muscle cells to dilate the vessel and the remodeling of the vessel wall to stabilize the larger lumen. The two leading causes of AVF maturation failure are poor outward remodeling and excessive inward remodeling. AVF maturation requires remodeling of the vessel wall to sufficiently increase AVF flow rate and lumen area for dialysis. Maturation failure of the arteriovenous fistula (AVF) remains a significant problem for chronic kidney disease patients on hemodialysis, with failure rates as high as 60% ( Dember et al., 2008 Cheung et al., 2017). Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation. There was no significant difference between control and sildenafil groups for the other geometric parameters. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. In both groups: 1) CSA increased from the 0–5 to 15–20 zone 2) velocity, WSS, and vorticity were highest in the 0–5 zone and dropped significantly thereafter and 3) OSI increased at the 5–10 zone and then decreased gradually. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. To test our hypothesis, we used the PDE5A inhibitor sildenafil to treat AVFs in a rat model and performed magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) to generate a detailed spatial profile of hemodynamics in AVFs. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. Aberrant blood flow is thought to impair AVF remodeling, but previous literature has largely focused on hemodynamics averaged over the entire AVF or at a single location. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area.
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