765-3 Superoxide Dismutase Reduces Superoxide Anion Levels in Balloon-injured Porcine Coronary Arteries

Abstract

Superoxide anion (O2–), a moiety that rapidly inactivates nitric oxide, is present in elevated concentrations in the vessel wall following balloon vascular injury. Recent data suggest that O2– is involved in the abnormal endothelium-dependent vasomotor responses of the regenerated endothelium.To investigate the hypothesis that polyethyleneglycol superoxide dismutase (PEG-SOD) can effectively scavenge O2– in the vessel wall, ten pigs were subjected to balloon injury of the left anterior descending or left circumflex coronary artery, then maintained on normal lab diets for 28 days. On day 29 five pigs (RX group) began receiving daily intravenous infusions of PEGSOD (12,000U/kg day 1, then 6,000 U/kg days 2–5) while five pigs received no PEG-SOD therapy (NO RX group). All animals were sacrificed on day33. O2–generation was assessed by lucigenin-amplified chemiluminescence in segments of injured and uninjured coronary arteries. Uninjured/NO RX segments (n=7) and uninjured/RX segments (n=7) had similar O2– levels (2728±457 and 3540±543 counts per minute/mg tissue dry weight, respectively, p=NS). Injured/NO RX segments (n=5) had significantly elevated O2– production (7040±1608 cpm/mg, p<0.05 vs baseline). PEG-SOD therapy in injured/ RX segments (n=7) dramatically restored O2– levels to normal (3167±681 cpm/mg, p=NS vs uninjured, p<0.05 vs injured/NO AX).Thus. PEG-SOD therapy effectively reduces O2– levels in the vessel wall following balloon injury. Prevention of nitric oxide degradation via this mechanism may have important implications for modulation of coronary vascular tone following balloon injury