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Catheter Cardiovasc Interv ; 81(4): 698-708, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22581717

ABSTRACT

OBJECTIVE: The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model. BACKGROUND: Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties. METHODS: Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS). RESULTS: The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05). CONCLUSION: In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.


Subject(s)
Cardiovascular Agents/toxicity , Coronary Vessels/drug effects , Drug-Eluting Stents , Inflammation/chemically induced , Percutaneous Coronary Intervention/instrumentation , Probucol/analogs & derivatives , Animals , Cardiovascular Agents/administration & dosage , Cardiovascular Agents/pharmacokinetics , Cattle , Cell Survival/drug effects , Cells, Cultured , Coronary Vessels/metabolism , Coronary Vessels/pathology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Endothelial Cells/drug effects , Endothelial Cells/pathology , Fibrin/metabolism , Inflammation/pathology , Male , Metals , Models, Animal , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Neointima , Percutaneous Coronary Intervention/adverse effects , Probucol/administration & dosage , Probucol/pharmacokinetics , Probucol/toxicity , Prosthesis Design , Sirolimus/administration & dosage , Swine
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