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 initiation and progression of atherosclerosis. In this study we examined the effects of local intraoperative treatment with polyethylene glycolated superoxide dismutase (PEG-SOD) on lipid peroxidation and on the development of intimal hyperplasia in experimental vein grafts.


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 animals 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 performed on 28-day vein grafts.


RESULTS
MDA concentration was increased 5. 7-fold (P < 0.05) in 3-day control vein grafts compared to ungrafted jugular veins. Intraoperative PEG-SOD treatment raised SOD activity 5.0-fold (P < 0.05) and reduced MDA concentration 8-fold (P < 0.05) in 3-day vein grafts compared to controls. At 28 days, intimal thickness was reduced by 35% with PEG-SOD 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-SOD-treated vein grafts to norepinephrine, serotonin, bradykinin, nitroprusside, and acetylcholine were not significantly changed when compared to controls. Treatment with PEG alone did not significantly alter lipid peroxidation, wall dimensions, or vasomotor function of vein grafts.


CONCLUSIONS
This study demonstrates that intraoperative local treatment of vein grafts with PEG-SOD increases SOD activity and decreases lipid peroxidation for at least 3 days, resulting in reduced intimal hyperplasia at 28 days. These findings further implicate oxidative stress in the hyperplastic response of vein grafts and suggest a potential therapeutic role for PEG-SOD in the prevention of vein graft failure.
Huynh
T T
TT
Vascular Biology and Atherosclerosis Research Laboratory, Duke University Medical Center, Durham, North Carolina, 27710, USA.
Davies
M G
MG
Trovato
M J
MJ
Barber
L
L
Safi
H J
HJ
Hagen
P O
PO
D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology; D006965:Hyperplasia; D007432:Intraoperative Period; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D014680:Veins / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000637:transplantation*
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase