Selective ET A Receptor Antagonism Reduces Neointimal Hyperplasia in a Porcine Coronary Stent Model

Publisher Website
Google Scholar
Abstract
Background —As endothelin binds to ET A receptors, it stimulates vascular smooth muscle cell proliferation and may thus be pivotally involved in the pathogenesis of restenosis. This study assessed the ability of a potent and selective ET A antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented injury model. Methods and Results —Fifty-five pigs were randomized to receive placebo or the oral ET A -selective antagonist ABT147627 twice daily for 28 days in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high). Each underwent oversized stent deployment in two randomly assigned major epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs per group) survived without complication until predetermined euthanasia at 28 days. In the placebo group, mean injury score was 1.73±0.80, with a mean neointimal response of 0.45±0.24 mm. By comparison, the low-dose group had a similar mean injury score of 1.79±0.75 with reduced neointimal response, 0.36±0.22 mm ( P P P =0.05). In the high-dose pigs, mean injury score was also significantly greater than in the placebo arm (1.93±0.73; P P Conclusions —Oral, selective ET A receptor antagonism significantly reduced neointimal hyperplasia forming over porcine coronary stented injuries in the first 28 days. This strategy may have clinical potential for the limitation and treatment of coronary restenosis after percutaneous revascularization.