In-stent restenosis limitation with stent-based controlled-release nitric oxide: initial results in rabbits.
OBJECTIVE
To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits.


METHODS
Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance.


RESULTS
NO-containing microspheres released NO with an initial bolus in the 1st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated group relative to controls (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01 [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days, P <.01).


CONCLUSIONS
Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.
Do
Young S
YS
Department of Cardiovascular and Interventional Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Rm H-3647, Stanford, CA 94305, USA.
Kao
Edward Y
EY
Ganaha
Fumikiyo
F
Minamiguchi
Hiroki
H
Sugimoto
Koji
K
Lee
Jane
J
Elkins
Christopher J
CJ
Amabile
Philippe G
PG
Kuo
Michael D
MD
Wang
David S
DS
Waugh
Jacob M
JM
Dake
Michael D
MD
D015901:Angiography, Digital Subtraction; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001027:Aortography; D001157:Arterial Occlusive Diseases / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D011475:Prosthesis Failure; D011817:Rabbits; D055502:Secondary Prevention; D015607:Stents
D020099:Coated Materials, Biocompatible; C118603:NOC 12; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D006152:Cyclic GMP