Chronological changes in morphometry and histology in the rabbit vascular wall after external radiation for the prevention of intimal hyperplasia.
BACKGROUND
Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries, information is lacking on how irradiation affects arterial histology and neointimal smooth-muscle cell proliferation-the hallmark of restenosis. We chronologically investigated early histological changes and quantitative changes in arterial wall cell proliferation after arterial injury followed by external radiation for the prevention of intimal hyperplasia in rabbits.


METHODS
The aorta was experimentally injured in 26 rabbits who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies at 3, 7, 15, 30, and 45 days after experimental injury.


RESULTS
Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control rabbits. In the irradiated group histological examination showed delayed neointimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media at 7 days contained necrotic areas and delayed fibrosis with calcifications. There was no statistical difference between the number of proliferating cells in the irradiated groups and the control group. Proliferating cells reached maximum numbers later in irradiated groups than in control rabbits (45 days versus 3 days).


CONCLUSIONS
After arterial injury, external irradiation at 20 Gy effectively reduced aortic neointimal thickening. Irradiation-induced histological changes include recasting with rapid necrosis and delayed fibrosis. Radiation-induced parietal recasting with necrosis, fibrosis, and calcifications might worsen in time. Although irradiation after arterial injury leaves proliferative smooth-muscle cells within the arterial wall quantitatively unchanged in the early days after the procedure, it then induces a delayed reaction (observed over 45 days in our study). Whether neointimal hyperplasia is merely delayed or will ultimately develop causing restenosis awaits confirmation from experimental and clinical studies with a long-term follow-up.
de Ravignan
David de la Croix
Dde L
Unit of Vascular Surgery, Catholic Institute of Lille, Lille, France.
Creusy
Colette
C
Chevalier
Jacques
J
Cosset
Jean-Marc
JM
Eschwege
François
F
Puppinck
Paul
P
Speziale
Francesco
F
Fiorani
Paolo
P
Lartigau
Eric
E
Ducasse
Eric
E
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology* / Q000528:radiation effects*; D002404:Catheterization / Q000009:adverse effects; D049109:Cell Proliferation / Q000528:radiation effects; D005260:Female; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D011839:Radiation, Ionizing; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*