title: A coupled experimental and computational approach to quantify deleterious hemodynamics, vascular alterations, and mechanisms of long-term morbidity in response to aortic coarctation.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Engineering, Marquette University, United States.
authors.forename: Arjun
authors.initials: A
authors.lastname: Menon
authors.forename: David C
authors.initials: DC
authors.lastname: Wendell
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Wang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Eddinger
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Toth
authors.forename: Ronak J
authors.initials: RJ
authors.lastname: Dholakia
authors.forename: Paul M
authors.initials: PM
authors.lastname: Larsen
authors.forename: Eric S
authors.initials: ES
authors.lastname: Jensen
authors.forename: John F
authors.initials: JF
authors.lastname: Ladisa
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology*; D001017:Aortic Coarctation / Q000503:physiopathology*; D001794:Blood Pressure; D003198:Computer Simulation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D006439:Hemodynamics; D057446:Hydrodynamics; D008297:Male; D009213:Myography; D011817:Rabbits; D013997:Time Factors
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