(Circulation. 1995;92:1570-1575.)
© 1995 American Heart Association, Inc.
Articles |
Low-Dose Radioactive Endovascular Stents Prevent Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rabbits
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
From the Departments of Cardiology (C.H., C.G., K.D., E.H., W.K.) and Anatomy (J.M.), University of Heidelberg; the Department of Cardiology, University of Tübingen (R.R.); and the Nuclear Research Center Karlsruhe (P.F.), Germany.
Correspondence to Christoph Hehrlein, MD, Department of Cardiology, University of Heidelberg, Bergheimer Str 58, 69115 Heidelberg, Germany.
Background Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model.
Methods and Results Palmaz-Schatz stents were made radioactive in
a cyclotron. The stents had a very low activity (maximum, 35 µCi),
and thus, manipulation did not require extensive radiation protection.
One, 4, 12, and 52 weeks after the implantation of nonradioactive
stents and radioactive stents in rabbit iliac arteries,
neointimal thickening was analyzed by quantitative
histomorphometry. Immunostaining for
endothelial cell von Willebrand factor,
macrophages, SMC 
-actin, collagen type I, and proliferating
cell nuclear antigen (PCNA) was performed to determine
radiation-induced changes in the arterial wall. SMC
proliferation was quantified by computer-assisted cell counting of
PCNA-immunoreactive cells. Neointima formation was markedly
suppressed by the implantation of radioactive stents in a
dose-dependent fashion at all observed time points. At peak
proliferative activity of SMCs 1 week after nonradioactive stent
implantation, 30±2% of SMCs in the neointima were
proliferating, compared with 0.5±0.1% of SMCs after implantation of
stents with an initial activity of 35 µCi (P<.001). The
neointima covering radioactive stents was characterized by
decreased smooth muscle cellularity and increased extracellular matrix
formation. Further, we observed a delayed
endothelialization depending on the radiation dose. No
difference in vascular thrombosis was found after nonradioactive and
radioactive stent implantation.
Conclusions The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.
Key Words: cells • muscle, smooth • radioisotopes • stents
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