Oxidative Stress and Atrial Fibrillation After Cardiac Surgery: A Case-Control Study

Abstract

New-onset postoperative atrial fibrillation (PAF) continues to be among the most common complications after cardiac surgery, leading to significant morbidity and cost. We studied the role of oxidative stress on patients after cardiopulmonary bypass. Patients undergoing coronary artery bypass grafting or valve procedures who exhibited new-onset PAF (n = 11) and those who remained in sinus rhythm (n = 13) were prospectively matched based on preoperative, intraoperative, and postoperative characteristics. Postoperative atrial fibrillation was assessed by electrocardiogram and must have required initiation of antiarrhythmic therapy or anticoagulation. Right atrial and skeletal muscle samples were harvested before and after cardiopulmonary bypass for oxidative protein immunostaining (Oxyblot assay). Serum samples were collected preoperatively and postoperatively at 6 hours and day 4 for microarray assessment of gene expression and to quantify total peroxide levels. Patients with PAF had significantly more elevation in total peroxide levels in serum compared with patients in sinus rhythm at 6 hours (5.83 +/- 1.9 versus 2.02 +/- 0.2 fold, respectively; p = 0.039) but not at day 4 (3.81 +/- 1.2 versus 2.17 +/- 0.5 fold, respectively; p = 0.188). Patients with PAF also had significantly more myocardial oxidation compared with patients in sinus rhythm at 6 hours (4.19 +/- 1.4 versus 0.94 +/- 0.3 fold, respectively; p = 0.021). Increased serum peroxide levels in patients who exhibited PAF correlated with elevated myocardial protein oxidation but not peripheral muscle oxidation. Gene expression analysis revealed a differential genomic response in patients with new-onset PAF (more oxidation) compared with patients in sinus rhythm (more reduction). Patients who exhibit PAF after cardiac surgery have significantly increased acute oxidative stress, which translates into increased myocardial oxidation. Also, patients with PAF have a differential oxidative genomic response after cardiopulmonary bypass that may predispose them to oxidative stress.