title: Chronological changes in morphometry and histology in the rabbit vascular wall after external radiation for the prevention of intimal hyperplasia.
abstract: 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.
authors.affiliation: Unit of Vascular Surgery, Catholic Institute of Lille, Lille, France.
authors.forename: David de la Croix
authors.initials: Dde L
authors.lastname: de Ravignan
authors.forename: Colette
authors.initials: C
authors.lastname: Creusy
authors.forename: Jacques
authors.initials: J
authors.lastname: Chevalier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cosset
authors.forename: François
authors.initials: F
authors.lastname: Eschwege
authors.forename: Paul
authors.initials: P
authors.lastname: Puppinck
authors.forename: Francesco
authors.initials: F
authors.lastname: Speziale
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorani
authors.forename: Eric
authors.initials: E
authors.lastname: Lartigau
authors.forename: Eric
authors.initials: E
authors.lastname: Ducasse
mesh_terms: 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*