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Research Article Free access | 10.1172/JCI117078

Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty.

A E Villa, L A Guzman, W Chen, G Golomb, R J Levy, and E J Topol

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Villa, A. in: PubMed | Google Scholar

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Guzman, L. in: PubMed | Google Scholar

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Chen, W. in: PubMed | Google Scholar

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Golomb, G. in: PubMed | Google Scholar

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Levy, R. in: PubMed | Google Scholar

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.

Find articles by Topol, E. in: PubMed | Google Scholar

Published March 1, 1994 - More info

Published in Volume 93, Issue 3 on March 1, 1994
J Clin Invest. 1994;93(3):1243–1249. https://doi.org/10.1172/JCI117078.
© 1994 The American Society for Clinical Investigation
Published March 1, 1994 - Version history
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Abstract

A periadventitial polymer system is an alternative local drug delivery technique to obtain and maintain high tissue levels of the drug at the site of vascular injury. To determine if local periadventitial delivery of dexamethasone decreases neointimal proliferation after balloon vascular injury, in three groups of Sprague-Dawley rats, 5% dexamethasone, 0.5% dexamethasone, and placebo silicone polymers were implanted around the left common carotid artery after balloon injury. In a fourth group, placebo polymers were implanted without balloon injury. Dexamethasone serum and tissue levels after polymer implantation were significantly higher in the 5% dexamethasone group compared with the 0.5% dexamethasone group. There was no neointima formation in any of the arterial segments covered with placebo polymers for 3 wk, but without balloon injury. In the arterial segments covered by the 5 and 0.5% dexamethasone polymers, there was a 76 and 75% reduction in intima/media ratios, respectively, compared with the placebo group (5% dexamethasone, 0.26 +/- 0.04; 0.5% dexamethasone, 0.27 +/- 0.03; placebo, 1.09 +/- 0.16, respectively; P < 0.0001). These results suggest that: (a) silicone polymers wrapped around the common carotid arteries for 3 wk did not, without balloon injury, stimulate neointimal proliferation in the rat model; (b) the activity of the drug-eluting polymer for suppressing intimal proliferation was chiefly, but not exclusively, site specific; and (c) transadventitial local delivery of dexamethasone at two different doses markedly inhibits neointimal proliferation after balloon vascular injury.

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