Structural and mechanical analysis of treated and untreated aortic coarctation in a growing porcine model.

Abstract

Coarctation of the aorta (COA) is a congenital heart disease for which successful intervention can restore flow and reduce the blood pressure gradient, but does not ensure long-term health. Adults with successfully treated COA exhibit significantly higher incidence of hypertension. The objective of this study was to measure differences in the structure and mechanics of proximal and distal aortic tissue from the first age-appropriate, physiologically relevant growing porcine model of COA. This animal model also enabled the evaluation of a cutting-edge serially dilatable stent. Quantitative histologic analysis measured structural changes and the mechanical properties were investigated through uniaxial, shear lap, and peel tests of tissue from sham, control COA, and treated COA animals. Our original hypothesis that proximal aortic tissue from control and treated COA groups would be thicker and have less elastin was false. There were no significant differences in elastin content, collagen content, lumen area, or lumen-to-tissue area between groups. Mechanically, distal tissue also exhibited no difference in either uniaxial or shear lap stiffness, failure stress, or failure strain between groups. Distal tissue from the COA control and treated COA groups however, exhibited, a lower circumferential failure peel tension, suggesting interlamellar strength was reduced. When compared with other previously published animal models of COA, a clear distinction was timing - our growing porcine model is the first for which COA was induced and treated at physiologically relevant time points. Our results indicated minimal adverse vascular remodeling in either the COA control or treated COA groups, however, it is unclear if this was due to a lack of severity, if elastinogenesis compensated for damage, or if another unknown mechanism prevented remodeling. STATEMENT OF SIGNIFICANCE: Coarctation of the aorta is one of the most common congenital heart diseases, yet the mechanisms behind it and its associated comorbidities remain poorly understood. To our knowledge, this was the first study to characterize tissue from a growing porcine model, with coarctation induced and treated at a physiologically relevant ages. Additionally, we investigated a new and emerging technology to treat coarctation and correlated the mechanical characterization of the aortic tissue with structural changes observed via quantitative histologic analysis.