Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition

Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. Aberrant blood f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hannah Northrup, Maheshika Somarathna, Savanna Corless, Isabelle Falzon, John Totenhagen, Timmy Lee, Yan-Ting Shiu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	arteriovenous fistula computational fluid dynamics shear stress outward remodeling vessel dilation Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/3502073b7d8445aa88a16fb4eaf74b5c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3502073b7d8445aa88a16fb4eaf74b5c
record_format	dspace
spelling	oai:doaj.org-article:3502073b7d8445aa88a16fb4eaf74b5c2021-12-02T10:52:29ZAnalysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition2296-418510.3389/fbioe.2021.779043https://doaj.org/article/3502073b7d8445aa88a16fb4eaf74b5c2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.779043/fullhttps://doaj.org/toc/2296-4185Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. 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. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. 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. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. 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. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. There was no significant difference between control and sildenafil groups for the other geometric parameters. Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation.Hannah NorthrupHannah NorthrupMaheshika SomarathnaSavanna CorlessIsabelle FalzonIsabelle FalzonJohn TotenhagenTimmy LeeTimmy LeeYan-Ting ShiuYan-Ting ShiuFrontiers Media S.A.articlearteriovenous fistulacomputational fluid dynamicsshear stressoutward remodelingvessel dilationBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arteriovenous fistula computational fluid dynamics shear stress outward remodeling vessel dilation Biotechnology TP248.13-248.65
spellingShingle	arteriovenous fistula computational fluid dynamics shear stress outward remodeling vessel dilation Biotechnology TP248.13-248.65 Hannah Northrup Hannah Northrup Maheshika Somarathna Savanna Corless Isabelle Falzon Isabelle Falzon John Totenhagen Timmy Lee Timmy Lee Yan-Ting Shiu Yan-Ting Shiu Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
description	Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. 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. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. 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. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. 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. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. There was no significant difference between control and sildenafil groups for the other geometric parameters. Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation.
format	article
author	Hannah Northrup Hannah Northrup Maheshika Somarathna Savanna Corless Isabelle Falzon Isabelle Falzon John Totenhagen Timmy Lee Timmy Lee Yan-Ting Shiu Yan-Ting Shiu
author_facet	Hannah Northrup Hannah Northrup Maheshika Somarathna Savanna Corless Isabelle Falzon Isabelle Falzon John Totenhagen Timmy Lee Timmy Lee Yan-Ting Shiu Yan-Ting Shiu
author_sort	Hannah Northrup
title	Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
title_short	Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
title_full	Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
title_fullStr	Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
title_full_unstemmed	Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
title_sort	analysis of geometric and hemodynamic profiles in rat arteriovenous fistula following pde5a inhibition
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3502073b7d8445aa88a16fb4eaf74b5c
work_keys_str_mv	AT hannahnorthrup analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT hannahnorthrup analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT maheshikasomarathna analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT savannacorless analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT isabellefalzon analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT isabellefalzon analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT johntotenhagen analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT timmylee analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT timmylee analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT yantingshiu analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition AT yantingshiu analysisofgeometricandhemodynamicprofilesinratarteriovenousfistulafollowingpde5ainhibition
_version_	1718396521583476736

Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition

Ejemplares similares