Abstract 17030: Atorvastatin Treatment for Three Days Before CABG Improves Myocardial Redox State, by Modifying NADPH-Oxidase Activity and NOS Coupling
Background: Myocardial redox is a key determinant of post-operative outcome in patients undergoing elective coronary bypass operations (CABG). Preoperative statin treatment reduces the incidence of post-operative atrial fibrillation (AF) in these patients, but the exact mechanisms of this effect are unknown. We examined the effect of short-term preoperative atorvastatin treatment on the mechanisms regulating myocardial redox state in these patients.
Methods: Forty two statin-naïve patients scheduled for elective CABG were randomized to receive atorvastatin 40mg/d or placebo (n=21 per group) for 3 days preoperatively. Blood samples were obtained at baseline and at the morning before operation. Myocardial samples of right atrial appendage were obtained during CABG. Myocardial superoxide (O2-) generation was determined by lucigenin-enhanced chemiluminescence while urate-inhibitable luminol chemiluminescence was used to estimate peroxynitrite (ONOO-) generation. NADPH oxidase activity was estimated by defining NADPH-stimulated O2-. Uncoupled nitric oxide synthase (NOS) contribution was estimated by using LNAME, and mitochondrial oxidases by using rotenone. DPI was used to estimate myocardial O2- generation from flavin-containing enzymes.
Results: Atorvastatin reduced resting (A), NADPH-stimulated (B) and DPI-inhibitable O2- (C). Although there was no significant effect on rotenone-inhibitable O2- (D), atorvastatin reversed LNAME-inhibitable O2- (E) and reduced ONOO- (F) generation. There was a borderline reduction of serum LDL (p<0.05) after treatment, but delta(LDL) was unrelated to myocardial oxidative stress.
Conclusions: Short term atorvastatin treatment rapidly reduced myocardial NADPH-oxidase activity and improved NOS coupling. This resulted into a reduction of both myocardial O2- and ONOO- generation, which partly explains the beneficial effect of preoperative statin treatment on post-operative CABG complications.
- © 2010 by American Heart Association, Inc.