title: Local drug delivery of argatroban from a polymeric-metallic composite stent reduces platelet deposition in a swine coronary model.
abstract: Thrombus formation after intracoronary stent implantation provides a stimulus for neointimal hyperplasia and if excessive can result in stent thrombosis. We tested the hypothesis that local delivery of an antithrombin drug from a polymeric-metallic stent inhibits platelet thrombus formation. An uncoated metal slotted tube, a jellyroll slotted metal stent with an Argatroban-loaded polymeric sleeve, and a jellyroll slotted metal stent with a drug-leached polymeric sleeve were randomly deployed into the coronary arteries of eight juvenile farm swine. Platelet deposition in the stented segments was determined at 2 hr using autologous 111Indium oxime-labeled platelets. Platelet deposition was significantly less in the Argatroban-loaded stents compared to the Argatroban-leached stents (1.40 x 10(8) platelets/cm2 vs. 26.8 x 10(8) platelets/cm2; P=0.005). When corrected for differences in the metal surface area exposed to blood, platelet deposition was significantly lower in the Argatroban-loaded stent (1.74+/-1.95 x 10(8)/cm2) compared to the Argatroban-leached stent (33.5+/-39.1 x 10(8)/cm2; P=0.005) and the uncoated metal stent (36.2+/-73.3 x 10(8)/cm2; P=0.006). In this coronary stent thrombosis model Argatroban has local antithrombotic properties when delivered with a polymer-metallic stent. Improved polymeric designs may reduce risk of thrombus deposition at the site of stent implantation.
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Kruse
authors.forename: J J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: J F
authors.initials: JF
authors.lastname: Tanguay
authors.forename: R M
authors.initials: RM
authors.lastname: Santos
authors.forename: D S
authors.initials: DS
authors.lastname: Millare
authors.forename: H R
authors.initials: HR
authors.lastname: Phillips
authors.forename: J P
authors.initials: JP
authors.lastname: Zidar
authors.forename: R S
authors.initials: RS
authors.lastname: Stack
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000502:physiology; D003328:Coronary Thrombosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D007205:Indium Radioisotopes; D008670:Metals; D010875:Pipecolic Acids / Q000008:administration & dosage*; D011108:Polymers; D011897:Random Allocation; D015607:Stents / Q000009:adverse effects*; D013449:Sulfonamides; D013552:Swine
chemical_list: D000991:Antithrombins; D007205:Indium Radioisotopes; D008670:Metals; D010875:Pipecolic Acids; D011108:Polymers; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban