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Abstract: PO1337

Natural Vascular Scaffolding Therapy for Arteriovenous Fistula Development in Rats

Session Information

  • Vascular Access
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 704 Dialysis: Vascular Access

Authors

  • Shiu, Yan-Ting Elizabeth, University of Utah, Salt Lake City, Utah, United States
  • Anderson, Blake, Alucent Biomedical Inc., Salt Lake City, Utah, United States
  • He, Yuxia, University of Utah, Salt Lake City, Utah, United States
  • Tey, CS Jason, University of Utah, Salt Lake City, Utah, United States
  • Kauser, Katalin, Alucent Biomedical Inc., Salt Lake City, Utah, United States
Background

Arteriovenous fistula (AVF) maturation failure results from insufficient lumen dilation and progressive inward neointimal hyperplasia (NH). Vascular wall distention is likely affected by the integrity of vascular extracellular matrix (ECM). We hypothesized that preserving ECM integrity at the time of AVF creation surgery could improve AVF maturation. Natural Vascular Scaffolding (NVS) Therapy is known to interlink collagen and elastin, the most abundant vascular ECM components, by covalently linking these proteins via photoactivation. We investigated the effect of NVS treatment on AVF development in a rat model.

Methods

Femoral AVFs were created in young Wistar male rats as an end-to-side anastomosis. Immediately after the blood flow was restored to dilate the femoral vein by arterial pressure, a 10 μl-drop of the NVS compound (2 mg/ml in phosphate buffered saline (PBS)) was placed at the anastomosis perivascularly and incubated for 5 minutes to allow full vessel wall penetration, followed with 1-min illumination of the anastomosis area by 450-nm light. The control group received a 10 μl-drop of PBS and the same light activation. The skin was closed immediately after light activation. Each group had 10 rats. Rats were euthanized 4 weeks post-AVF creation for histology, morphometry, immunohistochemistry of interleukin-6 (IL-6, an inflammation marker), and second-harmonic-generation evaluation by multiphoton microscopy of collagen fibers.

Results

Rats tolerated the NVS treatment well. The NH area was similar in both groups. The AVF vein’s open lumen area and % open lumen area in treated rats were significantly larger than in control rats (4.18-fold p=0.014 and 1.98-fold p=0.009, respectively). IL-6 intensity was significantly smaller in the NVS group than the PBS group (p=0.027). Collagen fibers in the NVS-treated AVFs trended towards perpendicular alignment with respect to the lumen circumference, with greater roundness, roughness, and eccentricity than in the PBS-treated AVF vessels.

Conclusion

Our studies showed that the NVS treatment significantly increased the AVF open lumen area, without significantly affecting the NH area. This suggests that NVS treatment may have therapeutic potential by facilitating lumen expansion while allowing a concomitant outward remodeling of the veins potentially leading to enhanced AVF maturation in patients.

Funding

  • Commercial Support