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Circulation. 1996;94:2364-2368

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(Circulation. 1996;94:2364-2368.)
© 1996 American Heart Association, Inc.


Articles

Effects of Endovascular Radiation From a ß-Particle–Emitting Stent in a Porcine Coronary Restenosis Model

A Dose-Response Study

Andrew J. Carter, DO; John R. Laird, MD; Lynn R. Bailey; Timothy G. Hoopes, MD; Andrew Farb, MD; David R. Fischell, PhD; Robert E. Fischell, ScD; Tim A. Fischell, MD; Renu Virmani, MD

Hematology and Vascular Biology, Walter Reed Army Institute of Research Cardiology Service, Walter Reed Army Medical Center, and The Armed Forces Institute of Pathology, Washington, DC; and the Division of Cardiology, Vanderbilt University School of Medicine, Nashville, Tenn (T.A.F.).

Correspondence to Andrew J. Carter, DO, Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001.

Background Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. The objective of this study was to evaluate the dose-related effects of a ß-particle–emitting radioactive stent in a porcine coronary restenosis model.

Methods and Results Thirty-seven swine underwent placement of 35 nonradioactive and 39 ß-particle–emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 µCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0-µCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-µCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low-activity (0.15- and 0.5-µCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm2 and high, 1.73±0.97 mm2 versus control, 2.40±0.87 mm2) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%, P<=.01). The 1.0-µCi stents, however, had greater neointimal formation (4.67±1.50 mm2) and more luminal narrowing (64±16%) than the control stents (P<.0001).

Conclusions The differential response to the doses of continuous ß-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.


Key Words: stenosis • stents • arteries




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