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(Circulation. 1996;93:641-645.)
© 1996 American Heart Association, Inc.
Articles |
Pure ß-ParticleEmitting Stents Inhibit Neointima Formation in Rabbits
From the Department of Cardiology (C.H., M.S., W.K.) and the Department of Anatomy (R.K.), University of Heidelberg (Germany), and the Forschungszentrum Karlsruhe/Cyclotron Department (K.S., E.H., L.F., P.F.), Karlsruhe, Germany.
Correspondence to Christoph Hehrlein, MD, Department of Cardiology, University of Heidelberg, Bergheimerstr 58, 69115 Heidelberg, Germany.
Background Considerable experimental evidence exists that
neointimal hyperplasia after angioplasty is inhibited by
-irradiation of the treated arteries. A ß-particle
radiation is absorbed in tissue within a shorter distance away from the
source than -radiation and may be more suitable for localized
vessel irradiation. This study outlines a method to implant a
ß-particle–emitting radioisotope (32P;
half-life, 14.3 days) into metallic stents. The effects of these
stents on the inhibition of neointimal hyperplasia was
compared with conventional stents in a rabbit model.
Methods and Results 32P was produced by irradiation
of red amorphous phophorus (31P) with neutrons and was
implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept
apart from 31P in a mass separator. The radioisotope was
tightly fixed to the stents, and the ion implantation process did not
alter the surface texture. Stent activity levels of 4 and 13 µCi were
chosen for the study. Four and 12 weeks after placement of conventional
stents and 32P-implanted stents in rabbit iliac arteries,
vascular injury and neointima formation were studied by
histomorphometry. Immunostaining for smooth muscle cell
(SMC) 
-actin was performed to determine SMC cellularity in the
neointima. SMCs were quantified by computer-assisted
counting of -actin immunoreactive cells.
Endothelialization of the stents was evaluated by
immunostaining for endothelial cell von
Willebrand factor. No difference in vessel wall injury was
found after placement of conventional and 32P-implanted
stents. Neointima formation was potently inhibited by
32P-implanted stents only at an activity level of 13 µCi
after 4 and 12 weeks. Neointimal SMC cellularity was
reduced in 32P-implanted stents compared with conventional
stents. Radioactive stents were endothelialized after 4
weeks, but endothelialization was less dense than in
conventional stents.
Conclusions Neointima formation in rabbits is markedly suppressed by a ß-particle–emitting stent incorporating the radioisotope 32P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.
Key Words: stents • radioisotopes
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