title: Patterns of activation and deposition of platelets exposed to the polymeric surface of the paclitaxel eluting stent.
abstract: The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, 8 Corporate Drive, Orangeburg, NY 10962, USA. jgranada@crf.org
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Alviar
authors.forename: David
authors.initials: D
authors.lastname: Wallace-Bradley
authors.forename: Matthew
authors.initials: M
authors.lastname: Osteen
authors.forename: Bijal
authors.initials: B
authors.lastname: Dave
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.forename: Htut K
authors.initials: HK
authors.lastname: Win
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
mesh_terms: D000328:Adult; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D001792:Blood Platelets / Q000502:physiology*; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D015539:Platelet Activation; D011108:Polymers; D013499:Surface Properties; D013552:Swine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019007:P-Selectin; D011108:Polymers; D017239:Paclitaxel