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Abstract: FR-PO706

The Role of PDE5A Inhibition in Arteriovenous Fistula Remodeling

Session Information

Category: Dialysis

  • 704 Dialysis: Vascular Access

Authors

  • Somarathna, Maheshika Srimali, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Redmann, Jessica N., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Lee, Timmy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Impaired outward vascular remodeling along with neointimal hyperplasia (NH) are thought to be the major underlying causes of arteriovenous fistula (AVF) maturation failure. We hypothesize that a selective phosphodiesterase type 5A (PDE5A) inhibitor, sildenafil, administered before and after AVF creation can be used to improve vascular outward remodeling. The aims of this study are to evaluate in a rat AVF model, the effect of PDE5A inhibition on: 1) venous and arterial diameter 2) venous blood flow and 3) venous NH formation.

Methods

Sildenafil was administered to 12-16-week-old Sprague-Dawley rats two weeks prior to AVF (Femoral vein to artery) creation and continued until sacrifice at 7 days. Venous blood flow was measured using transonic perivascular flow probes and the diameters of the AVF venous and arterial segments were measured at a point proximal and a point distal to the anastomosis using the microscopic ocular micrometer (Fig. 1A), at the time of sacrifice. Morphometric analysis of the AVF vein was also carried out to assess the changes in NH development.

Results

When compared to control group, a significant increase in venous and arterial diameter was observed in the sildenafil treated group in proximal and distal regions, at 7days after AVF creation. Furthermore, increased venous blood flow was also observed in sildenafil treated AVFs. However, no significant difference in the NH development was observed between the two groups.

Conclusion

Sildenafil administered before and after AVF creation, improves venous blood flow and the outward expansion in AVF vessels without affecting the level of NH at 7 days. These observations suggest that, outward expansion of venous limb of the AVF can preserve the luminal caliber and allow proper maturation of AVF, in the presence of NH formation. Therefore, targeting mechanisms that enhance outward vascular remodeling could be a potential therapeutic approach for treating AVF maturation failure.

Funding

  • Veterans Affairs Support