Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia.
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.
Nigri
Giuseppe R
GR
Division of Vascular Surgery of General Surgical Servies, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Kossodo
Sylvie
S
Waterman
Peter
P
Fungaloi
Patrick
P
LaMuraglia
Glenn M
GM
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*
D000911:Antibodies, Monoclonal; D016166:Free Radical Scavengers; D003676:Deferoxamine