Local Delivery of Antithrombotic Drug Inhibits Neointimal Hyperplasia Following Arterial Injury

The efficacy of local delivery of antithrombotic drugs on neointimal hyperplasia was investigated in 41 rabbits. One side of a rabbit iliac artery was injured by a balloon catheter as a control-injured artery. Another side of the iliac artery was also injured, and followed by local delivery of the antithrombotic drug (argatroban: 0.05 mg/kg; heparin 25 U/kg; or batroxobin 1 U/kg + heparin 25 U/kg). One hour after the balloon injury, angioscopy demonstrated occlusive or mural thrombus in all the controls, but few in the local drug-delivery arteries. Four weeks after balloon injury, angiographic percent stenosis in the locally drug-delivered arteries was 8%± 2% in the argatroban group (n = 7. P < 0.001 vs control side; 67%± 33%), 25%± 19% in the heparin group (n = 5, P < 0.005 vs control 66%± 14%), and 5%± 5% in the batroxobin group (n = 7, P < 0.01 vs control 59%± 39%). The activated partial thromboplastin time and fibrinogen did not change significantly. The PDGF-B chain was prominent at the neointimal layer in all the controls, but less so in the locally drug-delivered arteries. Thus, local delivery of antithrombotic drugs can inhibit neointimal hyperplasia after balloon injury by reducing thrombus related growth stimulation.