Abstract 4172: Short-Term Atorvastatin Treatment Reduces Vascular Oxidative Stress in Saphenous Vein Grafts by Improving eNOS Coupling and Reducing NADPH-Oxidase Activity in Patients Undergoing Elective CABG

Background: Statins improve survival of patients after coronary bypass surgery (CABG), but the exact mechanisms are unclear. We examined the effect of short-term treatment with high-dose atorvastatin, on vascular redox of saphenous vein grafts (SVG) used for CABG, and we explored the underlying mechanisms by using an ex-vivo SVG model. Methods: Twenty-four pts undergoing CABG (not receiving statins due to low LDL) were randomized to receive atorvastatin 40mg/day or placebo for 3 days before operation, in a double-blind fashion. Vascular O2- was measured in SVG segments by lucigenin chemiluminescence in the presence of endothelial nitric oxide synthase (eNOS) inhibitor LNAME (100 μ M, to estimate eNOS coupling) or NADPH (100 μ M, to estimate NADPH-oxidase activity). To test the direct effect of atorvastatin on SVG redox state, SVG segments from 10 more pts were incubated with atorvastatin 0, 5 and 50 μ M ex-vivo, and vascular O2- was measured. Results: Oral atorvastatin reduced O2- (A) and increased LNAME delta(O2-) (B, suggesting improved eNOS coupling), while LDL remained unchanged (p=NS). Ex-vivo atorvastatin incubation reduced O2- (C), improved eNOS coupling (D) and reduced NADPH-oxidase activity (from 41.4[26.4 –70.6] in control to 26.5[13.3– 62.9] in 5 μ M and 27.1[12.0 –30.6] RLU/Sec/mg in 50 μ M, p Conclusions: Short-term preoperative treatment with atorvastatin, reduces vascular O2- generation in SVG by improving eNOS coupling and decreasing NADPH-oxidase activity, in patients with low LDL, undergoing CABG. This is the first study demonstrating a direct effect of atorvastatin on redox state of SVG used in CABG, and may have major clinical implications.