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(Circulation. 1997;96:1944-1952.)
© 1997 American Heart Association, Inc.
Articles |
Effect of Intravascular Irradiation on Cell Proliferation, Apoptosis, and Vascular Remodeling After Balloon Overstretch Injury of Porcine Coronary Arteries
From the Department of Medicine (R.W., J.C.R., K.A.R., G.D.C., N.A.S., S.B.K., J.N.W.) and the Department of Radiation Oncology (I.R.C.), Emory University School of Medicine, Atlanta, Ga. Dr Waksman is now at the Cardiology Research Foundation, Washington, DC.
Correspondence to Josiah N. Wilcox, PhD, Emory University, Department of Medicine, Division of Hematology/Oncology, 1639 Pierce Dr, Room 1115 WMRB, Atlanta, GA 30322. E-mail medjnw{at}emory.edu
Background Ionizing radiation has been shown to reduce vascular lesion formation after balloon overstretch injury of pig coronary arteries. The present series of experiments examines the mechanism by which this occurs.
Methods and Results Balloon injury was performed on porcine
coronary arteries, followed immediately by ionizing radiation
using either a source train of 90Sr/Y or 192Ir
seeds designed to deliver 14 or 28 Gy at a depth of 2 mm from the
source. The animals were killed 3, 7, or 14 days after injury.
Bromodeoxyuridine was administered 24 hours before euthanasia to label
proliferating cells. Cell proliferation was significantly reduced on
day 3 in the adventitia and media of the irradiated vessels compared
with controls. Two weeks after injury, there were fewer
-actin–positive myofibroblasts in the adventitia of the irradiated
vessels than in nonirradiated controls, and morphometric
analysis indicated that the vessel perimeter of the irradiated
vessels was significantly larger than in controls. Together, these
results suggest a positive effect of intravascular irradiation on
vascular remodeling. Apoptosis was estimated by terminal
transferase dUTP-biotin nick-end labeling (TUNEL) 3 and 7 days after
injury. TUNEL-labeled cells were found primarily in the adventitia at
the medial tear, but no differences were detected between irradiated
and control vessels.
Conclusions These studies suggest that intracoronary radiation primarily inhibits the first wave of cell proliferation in the vessel wall and demonstrates a favorable effect on late remodeling by preventing adventitial fibrosis at the injury site.
Key Words: restenosis • remodeling • proliferation • angioplasty • radiation
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