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Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

DOI: 10.1186/1475-2840-11-75

Keywords: Paclitaxel-eluting stent, Everolimus-eluting stent, Restenosis, Vascular response, Percutaneous coronary intervention, Animal model

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Abstract:

Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V? (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5?M–10-12?M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42?mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5?M, 10-7?M) for 24 hours.After 3?months, EES reduced neointimal area (1.60?±?0.41?mm, p?<?0.001) with trends toward reduced % diameter stenosis (11.2?±?9.8%, p?=?0.12) and angiographic late-loss (0.28?±?0.30?mm, p?=?0.058) compared to PES (neointimal area: 2.74?±?0.58?mm, % diameter stenosis: 19.3?±?14.7%, late loss: 0.55?±?0.53?mm). Histopathology revealed increased inflammation scores (0.54?±?0.21 vs. 0.08?±?0.05), greater medial necrosis grade (0.52?±?0.26 vs. 0.0?±?0.0), and persistently elevated fibrin scores (1.60?±?0.60 vs. 0.63?±?0.41) with PES compared to EES (p?<?0.05). In vitro, paclitaxel significantly increased (p?<?0.05) EC/SMC apoptosis/necrosis at high concentrations (≥10-7?M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5?M) significantly increased caspase-3 activity (p?<?0.05) while everolimus had no effect.After 3?months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms

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