Abstract 10286: Myocardial Nitroso Redox Balance and Postoperative Atrial Electrical Remodelling Following Elective Cardiac Surgery on Cardiopulmonary Bypass: Molecular Mechanisms and Translational Implications of Perioperative Statin Therapy
Background: Systemic inflammation and increased myocardial production of reactive oxygen species (ROS) are associated with the development of postoperative atrial fibrillation (AF) and low cardiac output syndrome in patients undergoing cardiac surgery. Statins have been shown to exert rapid anti-inflammatory and antioxidant effects by inhibiting myocardial NOX2 oxidases and by increasing the bioavailability of nitric oxide (NO).
Methods and Results: We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on the atrial nitroso-redox balance in 116 patients and then investigated the effect of perioperative treatment with atorvastatin (80 mg once daily, for up to 6 days before surgery and 5 days thereafter) on nitric oxide synthase (NOS) activity, biopterin content, and the sources of ROS production (all by HPLC) in samples of the right atrial appendage obtained before and after CPB and reperfusion and on the postoperative atrial effective refractory period (AERP; by programmed electrical stimulation delivered using right atrial epicardial leads) in a placebo-controlled double-blind trial (ClinicalTrials.gov Identifier: NCT01780740) in 80 patients undergoing first-time elective cardiac surgery.
Our findings show that increased ROS production by NOX2 and mitochondrial oxidases and uncoupling of the endothelial NOS isoform (eNOS), secondary to enzyme’s S-glutathionylation, are the main mechanism underlying the atrial nitroso-redox imbalance after CPB and reperfusion. Compared with placebo, atorvastatin prevented the rise in atrial NOX2 activity and maintained the functionally coupled status of eNOS. The AERP lengthened progressively over first four postoperative days and did not differ between the treatment groups (n= 29).
Conclusions: Short-term statin therapy, at the dose conventionally used to lower LDL-cholesterol, prevents NOS uncoupling and nitroso-redox imbalance in the atrial myocardium of patients undergoing on-pump cardiac surgery. However, these changes have no significant impact on atrial refractoriness.
Author Disclosures: R. Jayaram: None. N. Goodfellow: None. M. Zhang: None. S. Reilly: None. M. Jones: None. N. Pal: None. R. Sayeed: None. R. DeSilva: None. B. Casadei: Research Grant; Significant; British Heart Foundation, Unrestricted research grant from AZ, EU Horizon 2020, Fondation Leducq.
- © 2015 by American Heart Association, Inc.