Reduction of lipid peroxidation with intraoperative superoxide dismutase treatment decreases intimal hyperplasia in experimental vein grafts

Background Vein graft failure is commonly attributed to the development of intimal hyperplastic lesions. Oxidative stress has been implicated in the i nitiation and progression of atherosclerosis. In this study we examined the effects of local intraoperative treatment with polyethylene glycolated sup eroxide dismutase (PEG-SOD) on lipid peroxidation and on the development of intimal hyperplasia in experimental vein grafts. Materials and methods. Forty-one New Zealand White male rabbits had a right carotid interposition bypass graft using the ipsilateral reversed jugular vein, Sixteen animals received local PEG-SOD (4,100 units) treatment; 9 ani mals received the polyethylene glycol (PEG) vehicle without SOD; 16 animals were used as controls, Postoperatively, malondialdehyde (MDA, a product of lipid peroxidation) concentration and SOD activity were assessed in 3-day vein grafts by colorimetric spectrophotometry. To determine wall dimensions and vasomotor function, morphometric and isometric tension studies were pe rformed on 28-day vein grafts, Results. MDA concentration was increased 5.7-fold (P < 0.05) in 3-day contr ol vein grafts compared to ungrafted jugular veins, Intraoperative PEG-SOD treatment raised SOD activity 8.0-fold (P < 0.05) and reduced MDA concentra tion 8-fold (P < 0.05) in 3-day vein grafts compared to controls, At 28 day s, intimal thickness was reduced by 35% with PEG-SOP treatment (54 +/- 4 vs 83 +/- 5; P < 0.001) compared to control vein grafts, without a change in medial thickness (77 +/- 4 vs 88 +/- 5; P = ns). The vasomotor functions of 28-day PEG-SOP-treated vein grafts to norepinephrine, serotonin, bradykini n, nitroprusside, and acetylcholine were not significantly changed when com pared to controls, Treatment with PEG alone did not significantly alter lip id peroxidation, wall dimensions, or vasomotor function of vein grafts. Conclusion. This study demonstrates that intraoperative local treatment of vein grafts with PEG-SOP increases SOD activity and decreases lipid peroxid ation for at least 3 days, resulting in reduced intimal hyperplasia at 28 d ays. These findings further implicate oxidative stress in the hyperplastic response of vein grafts and suggest a potential therapeutic role for PEG-SO P in the prevention of vein graft failure. (C) 1999 Academic Press.