ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1016

Inhibition of Phosphodiesterase Type 5A Prevents Pathological Cardiac Remodeling Following Arteriovenous Fistula Creation

Session Information

Category: Dialysis

  • 703 Dialysis: Vascular Access

Authors

  • Somarathna, Maheshika Srimali, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Lewis, Taylor G., Rosalind Franklin University of Medicine and Science Chicago Medical School, North Chicago, Illinois, United States
  • Ingle, Kevin Andrew, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Lee, Timmy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Cardiac events are the most common etiology of mortality in hemodialysis patients. The gold standard of vascular access, the arteriovenous fistula (AVF), may adversely affect cardiac structural and functional remodeling leading to heart failure. We hypothesize that inhibition of cGMP catabolism with a selective phosphodiesterase type 5A (PDE5A) inhibitor, sildenafil, may induce more favorable cardiac remodeling following AVF creation

Methods

Sildenafil was administered to 12-16 weeks old Sprague-Dawley rats two weeks prior to AVF creation and continued until sacrifice at 28 days. Cardiac structural and functional changes were evaluated by 1) 2D-echocardiography 2) measurement of collagen volume and oxidative stress and 3) evaluation of cardiomyocyte cytoskeletal-mitochondrial architecture

Results

Sildenafil treatment significantly improve pathological collagen degradation, reduces HNE4 expression, reverse desmin degradation and focal mitochondrial clustering following AVF creation, as compared to the control. We also observed a significant increase in cardiac output and stroke volume without reversing LV dilation which may suggest improvement in cardiac contractility.

Conclusion

PDE5A inhibition may provide a new treatment strategy for pathological cardiac remodeling following AVF creation

Funding

  • NIDDK Support