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Aortic Remodeling Kinetics in Response to Coarctation-Induced Mechanical Perturbations

Authors :
Arash Ghorbannia
Mehdi Maadooliat
Ronald K. Woods
Said H. Audi
Brandon J. Tefft
Claudio Chiastra
El Sayed H. Ibrahim
John F. LaDisa
Source :
Biomedicines, Vol 11, Iss 7, p 1817 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

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.

Details

Language :
English
ISSN :
22279059
Volume :
11
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.1b3a0a2789114111bed9e764d11eda3d
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines11071817