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 anticoa gulant and antiproliferative effects of heparin. The purpose of this s tudy was to assess the effect of local intramural delivery of heparin, using heparin-coated hydrogel balloons, on platelet deposition and ea rly smooth muscle cell proliferation after in vivo balloon angioplasty . Methods and Results The effects of local heparin delivery were asses sed during balloon angioplasty of porcine peripheral arteries. Ah ball oon dilatations were performed with oversized hydrogel balloons coated with a known quantity of heparin. Balloon dilatations in contralatera l vessels with uncoated hydrogel balloons served as study controls. Th e pharmacokinetics of heparin delivery were assessed using H-3-heparin to quantitate heparin wash-off from the balloon surface, heparin deli very to the arterial wall, and intramural persistence of drug. Platele t deposition at 1 hour after balloon injury was quantified using In-11 1-Iabeled platelets. Smooth muscle cell proliferation was assessed 6 t o 7 days after angioplasty with immunohistochemical staining for proli ferating cell nuclear antigen. H-3-heparin wash-off from the hydrogel balloon surface occurred rapidly, with approximately 95% of the hepari n coating disappearing within 10 seconds in the intact circulation. Ap proximately 2% of heparin on the balloon surface was delivered intramu rally at the time of angioplasty. Intramural heparin dissipated rapidl y, although small amounts of intramural heparin could still be detecte d for at least 48 hours. In comparison to control vessels, there was l ess In-111-platelet deposition (P=.002) and less medial smooth muscle cell proliferation (P=.03) in heparin-treated vessels. Conclusions Loc al intraluminal delivery of heparin at the time of balloon angioplasty with heparin-coated hydrogel balloons results in intramural depositio n of drug that persists for at least 48 hours. This in vivo technique significantly decreases platelet deposition and early smooth muscle ce ll proliferation after angioplasty injury.