Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas.
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 mu; G2, 170.24 +/- 21.2 mu; G3, 111.56 +/- 12.7 mu; 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].


CONCLUSIONS
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.
Berrocal
Daniel H
DH
Interventional Cardiology Department, Hospital Italiano de Buenos Aires, Argentina.
González
Germán E
GE
Morales
Celina
C
Gelpi
Ricardo J
RJ
Grinfeld
Liliana R
LR
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006937:Hypercholesterolemia / Q000473:pathology*; D007249:Inflammation; D000077146:Irinotecan; D009336:Necrosis; D010767:Phosphorylcholine; D011817:Rabbits; D012107:Research Design; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D004041:Dietary Fats; D004337:Drug Carriers; D010767:Phosphorylcholine; D000077146:Irinotecan; D002166:Camptothecin