title: Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) inhibits post-interventional stenosis in balloon-injured arteries, but causes thrombosis when applied to vein grafts. This may result from added free radicals produced during the hypoxia-reperfusion injury of vein graft implantation. The purposes of this study were to determine whether a free radical scavenger could inhibit vein graft thrombosis, enabling PDT to inhibit intimal hyperplasia; and to investigate the role of neutrophils, also a source of radicals, in this setting.
  
  
  METHODS
  Jugular vein bypass grafts of the common carotid artery were performed in rats. PDT was administered in situ to the vein graft and artery in the presence or absence of deferoxamine (DFX), an OH- scavenger.
  
  
  RESULTS
  PDT alone induced thrombosis in all untreated vein grafts. DFX administration or inhibition of neutrophil adhesion to the graft prevented PDT-induced vein graft thrombosis. Moreover, DFX given together with PDT significantly decreased vein graft intimal hyperplasia (0.010 mm2 +/- 0.005 mm2; P<.002) as compared with DFX alone (0.113 mm2 +/- 0.009 mm2) or untreated control animals (0.112 +/- 0.007 mm2).
  
  
  CONCLUSIONS
  OH- radicals and neutrophils both have key roles in PDT-induced vein graft thrombosis. By inhibiting free radical production or neutrophil adhesion to the graft, adequate PDT can be administered for successful inhibition of vein graft intimal hyperplasia.
authors.affiliation: Division of Vascular Surgery of General Surgical Servies, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Giuseppe R
authors.initials: GR
authors.lastname: Nigri
authors.forename: Sylvie
authors.initials: S
authors.lastname: Kossodo
authors.forename: Peter
authors.initials: P
authors.lastname: Waterman
authors.forename: Patrick
authors.initials: P
authors.lastname: Fungaloi
authors.forename: Glenn M
authors.initials: GM
authors.lastname: LaMuraglia
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003676:Deferoxamine / Q000008:administration & dosage*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006965:Hyperplasia / Q000188:drug therapy / Q000517:prevention & control; D007601:Jugular Veins; D023421:Models, Animal; D009504:Neutrophils / Q000276:immunology; D010778:Photochemotherapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D013927:Thrombosis / Q000517:prevention & control*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D016166:Free Radical Scavengers; D003676:Deferoxamine