(Circulation. 1995;92:3025-3031.)
© 1995 American Heart Association, Inc.
Articles |
Intracoronary Low-Dose ß-Irradiation Inhibits Neointima Formation After Coronary Artery Balloon Injury in the Swine Restenosis Model
Correspondence to Spencer B. King III, MD, Andreas Gruentzig Cardiovascular Center, F606 Emory University Hospital, 1364 Clifton Rd NE, Atlanta, GA 30322.
Background Neointima formation contributing to
recurrent stenosis remains a major limitation of
percutaneous transluminal angioplasty. Endovascular
low-dose 
-irradiation has been shown to reduce intimal
thickening (hyperplasia) after balloon overstretch injury in pig
coronary arteries, a model of restenosis. The
objective of this study was to determine whether the use of a
ß-emitting radioisotope for this application would have similar
effects and to examine the dose-response relations with this
approach.
Methods and Results Normal domestic pigs underwent balloon
overstretch injury in the left anterior descending and left circumflex
and coronary arteries. A flexible catheter was introduced by
random assignment into one of these arteries and was afterloaded with a
2.5-cm ribbon of encapsulated
90Strontium/90Yttrium sources
(90Sr/Y, a pure ß-emitter). It was left in place for
a period of time sufficient to deliver one of four doses: 7, 14, 28, or
56 Gy, to a depth of 2 mm. Animals were killed 14 days after balloon
injury, the coronary vasculature was pressure-perfusion
fixed, and histomorphometric analysis of arterial
cross sections was performed. All arteries treated with radiation
demonstrated significantly decreased neointima formation
compared with control arteries. The ratio of intimal area to medial
fracture length was inversely correlated with increasing radiation
dose: control (no radiation), 0.47; 7 Gy, 0.34; 14 Gy, 0.20; 28 Gy,
0.08; and 56 Gy, 0.02 (r=-.78, P<.000001).
Scanning electron microscopy demonstrated a confluent layer of
endothelium-like cells both in control and in 14
Gy–irradiated arteries. There was neither evidence of significant
necrosis nor excess fibrosis in the media, adventitia, or perivascular
space of the coronary arteries or adjacent
myocardium in the irradiated groups. Furthermore, the
exposure to the staff and the total body exposure to the pig with the
ß source was a small fraction of the dose previously measured and
calculated with 192Ir, a -emitting radioisotope.
Conclusions Administration of endovascular ß-radiation to the site of coronary arterial overstretch balloon injury in pigs with 90Sr/Y is technically feasible and safe. Radiation doses between 7 and 56 Gy showed evidence of inhibition of neointima formation. A dose-response relation was demonstrated, but no further inhibitory effect was seen beyond 28 Gy. These data suggest that intracoronary ß-irradiation is practical and feasible and may aid in preventing clinical restenosis.
Key Words: restenosis • angioplasty • coronary arteries • radiation • irradiation
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