Abstract 18195: Myocardial Redox State Predicts Post-Operative Clinical Outcome in Patients Undergoing Elective CABG: The Role of NADPH-Oxidase and Uncoupled Nitric Oxide Synthase
Background: Evidence suggests that myocardial redox may be a key feature in myocardial physiology, but its exact role on the development of post-operative complications after coronary bypass grafting (CABG) is unclear. We examined the impact of myocardial superoxide (O2-) and peroxynitrite (ONOO-) on clinical outcome post CABG and defined the mechanisms regulating their generation in the human myocardium.
Methods: Samples of right atrium appendages were obtained from 132 patients undergoing elective CABG. Myocardial O2- was determined by lucigenin chemiluminescence and ONOO- by urate-inhibitable luminol chemiluminescence. NADPH oxidase activity was defined by NADPH-stimulated O2- and its apocynin-inhibitable fraction, uncoupled nitric oxide synthase (NOS) by using LNAME and mitochondrial oxidases by using rotenone. Patients were followed up prospectively for 2 weeks or until their discharge from the hospital.
Results: During follow-up, 40 of these patients developed paroxysmal atrial fibrillation (PAF), 2 died and 47 required inotropic support for >24 hours. In cox-regression, PAF was predicted by high myocardial NADPH-oxidase activity (a), LNAME-inhibitable O2- (b) and ONOO- (c) but not by mitochondrial oxidases activity (P=NS). Length of hospitalization was best predicted by myocardial NADPH-oxidase activity (d) and ONOO- (f) but not by LNAME-inhibitable O2- (e). The requirement of inotropic support for >24 hours was associated with higher myocardial NADPH-oxidase activity (p<0.05) and higher ONOO- (P<0.01).
Conclusions: Myocardial NADPH-oxidase and uncoupled NOS, as sources of myocardial O2- and ONOO-, are major predictors of post-operative PAF and affect the length of hospitalization in patients undergoing CABG. These enzymes may prove to be novel therapeutic targets for the prevention of post-operative complications in these patients.
- © 2010 by American Heart Association, Inc.