Long-Term Persistence of Systolic Hypertension and Left Ventricular Fibrosis in an Animal Model of Early and Complete Repair of Aortic Coarctation

Background: Substantial cardiovascular morbidity occurs in survivors of childhood coarctation repair, even with anatomically successful relief of the aortic narrowing. Aim: In an animal model, we aimed to determine if there are persistent changes to blood pressure and/or the left ventricle following a period of transient aortic constriction in early life. Methods and Results: Aortic coarctation and its repair in early life was simulated by constricting the transverse aorta in 3-week-old Sprague-Dawley rats and relieving the constriction 3 weeks later. A control group underwent sham operations. 25 weeks after the relief of constriction, the animals underwent haemodynamic assessment via arterial catheterisation. The repaired group had an elevated central aortic systolic pressure compared to controls (116±5 mmHg vs 103±4 mmHg, p<0.05), despite not having a significant systolic gradient across the former constriction site (5±4 mmHg vs 0±2 mmHg, p=0.20). Left ventricles were then isolated. Left ventricular mass indexed to tibia length did not to differ between groups (p=0.07). Histological analysis similarly revealed that the average myocyte size did not differ between groups (p=0.57). Animals in the repair group did however have over a 2-fold increase in collagen deposition (4.86±0.24% vs 2.40±0.18%, p<0.001). A microarray was performed to screen for gene expression differences in the left ventricle. Subsequent validation by qRT-PCR found no genes to be differentially expressed. Conclusion: Despite successful early relief of aortic constriction, systolic hypertension and left ventricular fibrosis were found to be late significant late consequences of simulated aortic coarctation, in this animal model.