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 mm 2 ± 0.005 mm 2; P < .002) as compared with DFX alone (0.113 mm 2 ± 0.009 mm 2) or untreated control animals (0.112 ± 0.007 mm 2). 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.