Abstract: PO1016
Inhibition of Phosphodiesterase Type 5A Prevents Pathological Cardiac Remodeling Following Arteriovenous Fistula Creation
Session Information
- Vascular Access Arena: Challenges, Progress, and Prospects
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
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