Left Ventricular Fibrosis and Systolic Hypertension Persist in a Repaired Aortic Coarctation Model

Abstract

Despite successful repair in early life, patients with coarctation of the aorta (CoA) are predisposed to several cardiovascular complications in later life related to systemic hypertension or left ventricular (LV) dysfunction, or both, the pathogenesis of which is unclear. Three-week-old Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation, with release of the constriction 3 weeks later. Twenty-five weeks after the repair operation, animals underwent hemodynamic assessment, LV gene profiling, and histologic analysis. Animals with repaired aortic constriction exhibited a significantly elevated central systolic pressure (116 ± 5 mm Hg vs 103 ± 4 mm Hg; p < 0.05) despite the absence of any significant pressure gradient across the former constriction site compared with shams (5±4mm Hg vs 0 ± 2 mm Hg; p= 0.2). They also had more than a 2-fold increase in LV collagen deposition (4.86% ± 0.24% vs 2.40% ± 0.18%; p < 0.001). However, no significant differences were noted between the groups in maximum LV pressure (116 ± 3 mm Hg vs 107 ± 3 mm Hg; p= 0.1), LV mass indexed to tibial length (p= 0.07), or myocyte size. There was no significant differential expression of hypertrophy or fibrosis-related genes in the left ventricles of the repaired animals compared with shams. Despite successful early relief of simulated CoA in early life, relative hypertension and LV fibrosis were demonstrable late consequences in this animal model. This abnormal fibrosis persists in the absence of altered LV hemodynamics and gene expression.