Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas

• Published in: Catheterization and cardiovascular interventions Vol. 68; no. 1; pp. 89 - 96
• Main Authors: Berrocal, Daniel H., González, Germán E., Morales, Celina, Gelpi, Ricardo J., Grinfeld, Liliana R.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2006
• Subjects: Animals; Aorta, Abdominal - drug effects; Aorta, Abdominal - pathology; Atherosclerosis - pathology; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Camptothecin - pharmacology; Cell Proliferation - drug effects; Dietary Fats - administration & dosage; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; drugs eluting stents; Hypercholesterolemia - pathology; Inflammation; irinotecan; Necrosis; Phosphorylcholine; Rabbits; Research Design; restenosis; Stents; Tunica Intima - drug effects; Tunica Intima - pathology
• ISSN: 1522-1946; 1522-726X
• DOI: 10.1002/ccd.20694

Objective: To assess the effect of irinotecan‐eluting stents (IS) on neointimal growth in the aortas of hypercholesterolemic rabbits and to determine other local histopathological effects such as necrosis, fibrin, and inflammatory reaction. Methods: Phosphorylcholine‐coated stents were deployed in the aortas of hypercholesterolemic rabbits. Group 1 (control; n = 8) received unloaded stents, group 2 (n = 7) and group 3 (n = 9) received IS with 0.046 mg and 1.29 mg of irinotecan, respectively. Eight weeks after implantation the rabbits were killed. Neointimal thickness (NT) was assessed by morphometry. Semiquantitative injury score (from 0 to 3+) was used to analyze inflammatory infiltrate, fibrin deposits, and necrosis in the stented segments. Results: NT was reduced only in high‐doses IS (G1, 167.4 ± 20.8 μ; G2, 170.24 ± 21.2 μ; G3, 111.56 ± 12.7 μ; P < 0.05, G3 vs G1 and G2). Necrosis decreased significantly with IS [1.00 ± 0.10 in G1 to 0.33 ± 0.07 and 0.02 ± 0.01 in G2 and G3, respectively] only in the media layer. The inflammatory infiltrate was present in the three layers of aortas from G1, but only decreased significantly in the intimae layer of the high‐dose group [1.50 ± 0.15 in G1 vs 1.00 ± 0.18 in G3, P < 0.05]. Conclusion: Stents loaded with high‐dose irinotecan inhibit NT in the aortas of hypercholesterolemic rabbits. This effect was accompanied by decreased inflammatory infiltrate and media necrosis. © 2006 Wiley‐Liss, Inc.