Transcriptional remodeling of the interventricular septum in porcine models of right ventricular overload

Introduction Surgical repair of TOF is highly successful but may be complicated in adulthood by arrhythmias, sudden death, and right ventricular (RV) dysfunction. RV overload leads to interventricular septum (IVS) bulging and paradoxical movement but its contribution to RV dysfunction and arrhythmias remains unclear. Objective We aimed at characterizing IVS remodeling in a pig model of RV volume overload and a model of repaired TOF with combined pressure and volume overload. Methods Young piglets underwent surgery to induce RV volume overload (PINS, N = 5) or combined volume and pressure overload (rTOF, N = 5) and were compared to Sham animals (SHAM, N = 5). Animals came back for terminal experiments 4 months post-surgery. Cardiac function was assessed using MRI. Animals were euthanized, tissue samples were collected for molecular biology or fixed for histological analysis. Results RV end-systolic and diastolic volumes were increased and RV ejection fraction was decreased in rTOF and PINS pigs (P Conclusions These results suggest the presence of a pro-arrhythmic remodeling of the IVS in the overloaded RV which may lead to prolonged repolarization and increased excitability. Interestingly the conduction system may also be remodeled as indicated by the decrease in Connexin-40 expression.