A coupled experimental and computational approach to quantify deleterious hemodynamics, vascular alterations, and mechanisms of long-term morbidity in response to aortic coarctation. J Pharmacol Toxicol Methods 2012 Jan;65(1):18-28
Date
11/15/2011Pubmed ID
22079597Pubmed Central ID
PMC3288451DOI
10.1016/j.vascn.2011.10.003Scopus ID
2-s2.0-84857050157 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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 10weeks of age (~9 human years) to induce a 20mmHg 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 32weeks 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 12weeks 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.
Author List
Menon A, Wendell DC, Wang H, Eddinger TJ, Toth JM, Dholakia RJ, Larsen PM, Jensen ES, Ladisa JF JrAuthors
Thomas Eddinger PhD Bioological Sciences in the Biology department at Marquette UniversityEric S. Jensen DVM Associate Professor in the Research Office department at Medical College of Wisconsin
John F. LaDisa PhD Professor in the Pediatrics department at Medical College of Wisconsin
Jeffrey M. Toth PhD Associate Dean for Research in the School of Dentistry department at Marquette University
MESH terms used to index this publication - Major topics in bold
AnimalsAorta, Thoracic
Aortic Coarctation
Blood Pressure
Computer Simulation
Disease Models, Animal
Endothelium, Vascular
Hemodynamics
Hydrodynamics
Male
Myography
Rabbits
Time Factors
