A growth and remodeling computational model accurately predicted coarctation-induced vascular impairments, including 48% and 45% impairment in smooth muscle contraction and endothelial relaxation.
Does a growth and remodeling computational model accurately predict the kinetics of stress-mediated compensatory responses in a preclinical rabbit model of coarctation of the aorta?
A validated growth and remodeling computational model accurately predicts the kinetics of arterial thickening, stiffening, and vasoactive dysfunction in a rabbit model of aortic coarctation.
p-value: p=> 0.13
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.
Ghorbannia et al. (Sun,) conducted a other in Coarctation of the aorta (n=63). Coarctation-induced mechanical perturbations vs. Control group was evaluated on Vascular impairment (smooth muscle contraction and endothelial-dependent relaxation) (p=> 0.13). A growth and remodeling computational model accurately predicted coarctation-induced vascular impairments, including 48% and 45% impairment in smooth muscle contraction and endothelial relaxation.