Effects of atorvastatin on in-stent stenosis in normo- and hypercholesterolemic rabbits.
BACKGROUND
In-stent stenosis is characterized by a prolonged proliferation and inflammatory reactions around the stent struts. Potentially the antiproliferative and lipid-lowering effects of atorvastatin can synergistically limit neointima formation after stenting.


METHODS
Palmaz-Schatz stents were placed in the iliac arteries of white New Zealand rabbits. One half of the animals was fed an 0.5% hypercholesterolemic diet, the other half was normocholesterolemic. Both groups received either atorvastatin (3 mg/kg bodyweight) daily or placebo (n=10 each in the four groups). After 28 days the segments were excised.


RESULTS
Injury scores as a result of vessel trauma induced by stent-overstretch injury differed significantly between the four groups (median 1.0-1.9) and the stent-induced injury outweighed the beneficial effects of statin therapy on neointima formation by far. Smooth-muscle-cell proliferation was significantly increased in both hypercholesterolemic groups. Intimal and medial proliferation as well as inflammatory infiltrates around the stent strut were reduced by 20-40% in animals that received statin therapy although the injury score in both statin groups was 19 and 60% higher than in control animals.


CONCLUSIONS
Thus, the data of this study indicate that smooth muscle cell proliferation and inflammation in stented vessels can be reduced by atorvastatin both in hypercholesterolemic rabbits and in animals with normal lipid levels.
Herdeg
Christian
C
Department of Medicine, University of Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany. christian.herdeg@med.uni-tuebingen.de
Fitzke
Martin
M
Oberhoff
Martin
M
Baumbach
Andreas
A
Schroeder
Stephen
S
Karsch
Karl R
KR
D000818:Animals; D000069059:Atorvastatin; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*
D018680:Cholinergic Antagonists; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin