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Published online before print December 29, 2003, 10.1148/radiol.2302020417
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(Radiology 2004;230:377-382.)
© RSNA, 2003

Experimental Studies

In-Stent Restenosis Limitation with Stent-based Controlled-Release Nitric Oxide: Initial Results in Rabbits1

Young S. Do, MD2, Edward Y. Kao, MD, Fumikiyo Ganaha, MD, Hiroki Minamiguchi, MD, Koji Sugimoto, MD, Jane Lee, BS, Christopher J. Elkins, PhD, Philippe G. Amabile, MD, Michael D. Kuo, MD, David S. Wang, MD, Jacob M. Waugh, MD and Michael D. Dake, MD

1 From the Department of Cardiovascular and Interventional Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Rm H-3647, Stanford, CA 94305. Received April 11, 2002; revision requested July 9; final revision received August 26, 2003; accepted August 27. Address correspondence to M.D.D. (e-mail: mddake@stanford.edu).

PURPOSE: To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits.

MATERIALS AND 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).

CONCLUSION: Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.

© RSNA, 2003

Index terms: Animals • Arteries, femoral, 92.1268, 92.411 • Arteries, restenosis, 92.121, 92.411 • Experimental study • Stents and prostheses




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