Abstract

Our goals were to develop a rabbit model of subacute stent thrombosis and to evaluate the efficacy of a polymer stent coating with covalently bound heparin for its prevention. Bare metal stents (a nitinol wire coil with 3 stainless steel joints) were implanted in a carotid artery of 10 NZW rabbits with a 3.0 mm balloon catheter, inflated twice at 6 atm for 1 minute. Systemic antiplatelet and antithrombotic therapy was withheld. Animals were sacrificed at 24, 72 and 96 hours. Only the 96 hour group consistently developed occlusive or subocclusive thrombosis. Heparin (0.28 μ g/cm 2 ) was linked onto the surface of soluble polymer chains of segmented polyurethaneurea (SPUU) or aliphatic Tecoflex polyurethane membrane (50 μ m thick). using polyethylene oxide (PEO) as a hydrophilic spacer group. Eight stents were coated with this polymer-PEO-Heparin coating. Eight bare metal stents and 8 coated stents were deployed in a carotid artery of 16 NZW rabbits. All animals were sacrificed at 96 hours. At the time of sacrifice, both carotids (stented and contralateral nonstented) were exposed and resting blood flow measured. The amount of thrombus on each stent was assessed by a semiquantitative grading scale (I: no lumen encroachment; II: lumen encroachment; III: subocclusive thrombus; IV: occlusive thrombus) and by the weight of the dry thrombus. Carotid Flow (ml/min) Thrombus Grade (III/IV) Thrombus Weight (mg) Bare Stent (N = 8) 3.8 ± 8.2 7 of 8 42.2 ± 19.9 Heparin Stent (N = 8) 210 ± 92 0 of 8 6.0 ± 2.4 p -value 0.0014 0.0004 0.00016 The 96 hour rabbit carotid model yields a high frequency of occlusive and subocclusive subacute thrombosis. The stents coated with polymer-PEO-Heparin accumulate significantly less thrombus and have better patency than the uncoated stents at 96 hours in this model of subacute stent thrombosis.

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