Effectiveness of statin-eluting stent on early inflammatory response and neointimal thickness in a porcine coronary model.
BACKGROUND
Drug-eluting stent (DES) implantation is routine during coronary revascularization because DES significantly reduce rates of restenosis and target lesion revascularization compared with bare metal stent (BMS). However, available DES have limitations, such as late thrombosis because of delayed healing with poorer endothelialization and persistent local inflammation. Statins can inhibit cell proliferation, inflammation, and restore endothelial function. The present study evaluated the ability of stent-based cerivastatin delivery to reduce stent-induced inflammatory responses and adverse effects on endothelial function, and to inhibit neointimal hyperplasia in a porcine coronary model.


RESULTS
Pigs were randomized into groups in which the coronary arteries (9 pigs, 18 coronaries in each group) had either a cerivastatin-eluting stent (CES) or a BMS. All animals survived without any adverse effects. Inflammatory cell infiltration evaluated using scanning electron microscopy on day 3 after stenting was significantly decreased in the treated vessels (inflammation score: 1.15+/-0.12 vs 2.43+/-0.34, p<0.0001). At day 28, endothelial function with intracoronary infusion of bradykinin was preserved in both the CES and BMS groups. Volumetric intravascular ultrasound images revealed decreased intimal volume in the CES group (28.3+/-5.4 vs 75.9+/-4.2 mm3, p<0.0001). Histomorphometric analysis showed reduced neointimal area (1.74+/-0.45 vs 3.83+/-0.51 mm2, p<0.0001) in the CES group despite similar injury scores (1.77+/-0.30 vs 1.77+/-0.22, p=0.97).


CONCLUSIONS
In porcine coronary arteries CES significantly decreased neointimal hyperplasia with a decreased early inflammatory response and without endothelial dysfunction.
Miyauchi
Katsumi
K
Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan. ktmmy@med.juntendo.ac.jp
Kasai
Takatoshi
T
Yokayama
Takayuki
T
Aihara
Kouichiro
K
Kurata
Takeshi
T
Kajimoto
Kan
K
Okazaki
Shinya
S
Ishiyama
Haruo
H
Daida
Hiroyuki
H
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002908:Chronic Disease; D023903:Coronary Restenosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics; D006965:Hyperplasia; D008055:Lipids / Q000097:blood; D008855:Microscopy, Electron, Scanning; D011725:Pyridines / Q000493:pharmacokinetics; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011725:Pyridines; D014665:Vasodilator Agents; C086276:cerivastatin; D001920:Bradykinin