Document Type

Article

Language

eng

Format of Original

11 p.

Publication Date

1-2012

Publisher

Elsevier

Source Publication

Journal of Pharmacological and Toxicological Methods

Source ISSN

1056-8719

Original Item ID

doi: 10.1016/j.vascn.2011.10.003; PubMed Central: PMCID 3288451

Abstract

Introduction

Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors.

Methods

Rabbits underwent thoracic CoA at 10 weeks of age (~ 9 human years) to induce a 20 mm Hg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32 weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results.

Results

Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of normal BP (~ 4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits.

Discussion

These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods.

Comments

Accepted version. Journal of Pharmacological and Toxicological Methods, Volume 65, No. 1 (January 2012), DOI: 10.1016/j.vascn.2011.10.003. © Elsevier 2012. Used with permission.

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