DECREASED PLATELET DEPOSITION AND SMOOTH-MUSCLE CELL-PROLIFERATION AFTER INTRAMURAL HEPARIN DELIVERY WITH HYDROGEL-COATED BALLOONS

Background In vitro and in vivo studies have demonstrated both anticoagulant and antiproliferative effects of heparin. The purpose of this study was to assess the effect of local intramural delivery of heparin, using heparin-coated hydrogel balloons, on platelet deposition and early smooth muscle cell proliferation after in vivo balloon angioplasty. Methods and Results The effects of local heparin delivery were assessed during balloon angioplasty of porcine peripheral arteries. Ah balloon dilatations were performed with oversized hydrogel balloons coated with a known quantity of heparin. Balloon dilatations in contralateral vessels with uncoated hydrogel balloons served as study controls. The pharmacokinetics of heparin delivery were assessed using H-3-heparin to quantitate heparin wash-off from the balloon surface, heparin delivery to the arterial wall, and intramural persistence of drug. Platelet deposition at 1 hour after balloon injury was quantified using In-111-Iabeled platelets. Smooth muscle cell proliferation was assessed 6 to 7 days after angioplasty with immunohistochemical staining for proliferating cell nuclear antigen. H-3-heparin wash-off from the hydrogel balloon surface occurred rapidly, with approximately 95% of the heparin coating disappearing within 10 seconds in the intact circulation. Approximately 2% of heparin on the balloon surface was delivered intramurally at the time of angioplasty. Intramural heparin dissipated rapidly, although small amounts of intramural heparin could still be detected for at least 48 hours. In comparison to control vessels, there was less In-111-platelet deposition (P=.002) and less medial smooth muscle cell proliferation (P=.03) in heparin-treated vessels. Conclusions Local intraluminal delivery of heparin at the time of balloon angioplasty with heparin-coated hydrogel balloons results in intramural deposition of drug that persists for at least 48 hours. This in vivo technique significantly decreases platelet deposition and early smooth muscle cell proliferation after angioplasty injury.