A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon

ObjectiveRestenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound.MethodsA 140 μg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drug-delivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period.ResultsThe Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies.ConclusionsRSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis.

Clinical RelevanceThe incidence of intimal hyperplasia varies in different risk populations (eg, diabetic patients) up to 35% after bare-metal stent implantation and is reduced, but still exists and is problematic, after implantation of drug-eluting stents. Scouting experiences have shown that treatment with antioxidants improves endothelial cell coverage, decreases intimal hyperplasia, and reduces oxidative stress, thus promoting the patency of stents and grafts. In our experimental model, we observed that resveratrol locally administrated in the artery by a drug-eluting balloon has the potentialities to reduce the intimal hyperplasia thanks to a local anti-inflammatory response.