CONTROLLED RELEASE OF HEPARIN REDUCES NEOINTIMAL HYPERPLASIA IN STENTED RABBIT ARTERIES - RAMIFICATIONS FOR LOCAL THERAPY

Percutaneous coronary angioplasty is limited by neointimal hyperplasia and restenosis. Endovascular stenting has been proposed as a possible means of limiting this process. In practice stents have achieved early patency but are beset by early thrombosis and late restenosis. Heparin administered locally or systemically reduces smooth muscle cell hyperplasia following arterial injury in animals. Balloon-expandable stainless steel stents were placed in de-endothelialized rabbit iliac arteries to determine whether heparin released locally from perivascular matrices could reduce stent induced thrombosis and intimal hyperplasia. All animals received oral aspirin beginning 1 day prior to implantation and an IV bolus of heparin at balloon injury and stent placement. Heparin releasing ethylene-vinyl acetate copolymer matrices were placed adjacent to the stented portion of the artery in the treated group of rabbits. Thrombosis was evident in 30% of ten control arteries 14 days after stent placement and was reduced to 0% in nine segments receiving local heparin therapy (P < 0.05). Intimal hyperplasia was present in all experimental arterial sections, but total intimal area normalized for induced injury was reduced at 14 days from 12.6 +/- 0.9 mm2 in controls, to 6.8 +/- 1.0 mm2 in treated arteries (P < 0.001). Our results with perivascular drug administration may shed some light on the pathobiology of the vascular response to endovascular stent insertion and might assist in the design of novel means for enhancing the utilization of angioplasty and other interventional procedures.