876 Anti-proliferative and anti-inflammatory effects of Ramiprilat-coated stent in a porcine coronary overstretch restenosis model

Abstract

Background: The angiotensin-converting enzyme inhibitor ramiprilat has been previously demonstrated to protect myocardium from ischemia/reperfusion injury. Objectives: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stent in a porcine coronary overstretch restenosis model. Methods: Pigs were randomized into two groups in which the coronary arteries (16 pigs, 16 coronaries in each group) had either a ramiprilat-coated MAC stent or control MAC stent (AMG, Munich, Germany). Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries, and histopathologic analysis was assessed at 28 days after stenting. Results: There were no significant differences in the neointima area normalized to injury score and inflammation score between the two groups (1.58 ± 0.43, 1.60 ± 0.39 in ramiprilat stent group vs. 1.60 ± 0.57, 1.62 ± 0.49 in control stent group, respectively). In neointima, most inflammatory cells were lymphohistiocytes. Overall, significant positive correlations were found between the lymphohistiocyte count and the neointima area (r = 0.567, p < 0.001) and between the lymphohistiocyte count and the percent area stenosis (r = 0.478, p < 0.001). Although lymphohistiocyte count (170 ± 121 cells vs. 162 ± 83 cells) and fibrin scores (0.15 ± 0.06 vs. 0.17 ± 0.07, p = 0.8) were not different between both groups, there was a strong trend of smaller neointima area (1.06 ± 0.51 mm2 vs. 1.28 ± 0.35 mm2, p = 0.083) and percent area stenosis (18.9 ± 8.7% vs. 22.8 ± 7.2%, p = 0.088) in the ramiprilat stent group compared with control group. Conclusions: Ramiprilat-coated stent showed a trend of more inhibitory effects on neointimal hyperplasia without differences in effects on inflammatory cell infiltration and arterial healing compared with control stent in a porcine coronary restenosis model.