Document Type
Article
Publication Date
2023
Publisher
MDPI
Source Publication
Biomedicines
Source ISSN
2227-9059
Original Item ID
DOI: 10.3390/biomedicines11071817
Abstract
Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA.
Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5–11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters.
Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model.
Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity–duration thresholds that may ultimately avoid hypertension from CoA.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Ghorbannia, Arash; Maadooliat, Mehdi; Woods, Ronald K.; Audi, Said H.; Tefft, Brandon J.; Chiastra, Claudio; Ibrahim, El Sayed H.; and LaDisa, John F. Jr., "Aortic Remodeling Kinetics in Response to Coarctation-Induced Mechanical Perturbations" (2023). Biomedical Engineering Faculty Research and Publications. 676.
https://epublications.marquette.edu/bioengin_fac/676
ADA Accessible Version
Comments
Published version. Biomedicines, Vol. 11, No. 7 (2023). DOI.
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.