Abstract 2955: Increased Luminal Diameter With Drug-eluting Versus Bare-metal Stenting Of The Piglet Ductus Arteriosus

Abstract

Introduction: Maintaining ductus arteriosus (DA) patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immuno-suppressant drug, has anti-proliferative properties, inhibits smooth muscle cell (SMC) migration and may deter intimal hyperplasia occurring during spontaneous closure and post stent implantation of the DA. Methods: 16 Yorkshire piglets (age 7–11 days old, weight 2.2– 4.9 kg) underwent stent implantation of the DA (rapamycin-eluting (n = 8), bare metal (n = 8) stents, (3.5 mm diameter) and were sacrificed at 2, 4 and 6 weeks. Dissected DA were analyzed for SMC and extracellular matrix components (elastin, collagen and glycosaminoglycans). External diameter, wall thickness and lumen diameter were analyzed by morphometric software. DA-derived SMC were isolated and cultured for 7 days in the presence or absence of 100mM of rapamycin. Cellular proliferation rates were assessed by proliferative antigen Ki-67 detection and [ 3 H]-thymidine incorporation. Specific antibodies to elastin, collagen type I, and chondroitin sulfate-containing glycosaminoglycans were analyzed. Results: Rapamycin-eluting stents significantly inhibited neointimal formation compared with bare metal stents at 4 and 6 weeks resulting in larger luminal diameters (p<0.001). The in vitro studies demonstrated rapamycin-treated cultures of the DA-derived SMC had 50% lower proliferation rates (p<0.001). Conclusions : Rapamycin has anti-proliferative actions on the DA. Drug-eluting stents may be a more efficient tool for prolonging patency of the DA in neonates palliated for future correctional surgery.