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CLINICAL RESEARCH: ATRIAL FIBRILLATION AND CARDIAC SURGERY

Association of Atrial Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activity With the Development of Atrial Fibrillation After Cardiac Surgery

Young M. Kim, BSc^_*,1, Hassan Kattach, MRCS, Chandi Ratnatunga, FRCS, Ravi Pillai, FRCS, Keith M. Channon, MD, FRCP^_*,2 and Barbara Casadei, MD, DPhil, FRCP^_*,2,_*

^_* University Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Department of Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, United Kingdom.

Manuscript received April 23, 2007; revised manuscript received July 16, 2007, accepted July 24, 2007.

^_* Reprint requests and correspondence: Dr. Barbara Casadei, University Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. (Email: barbara.casadei{at}cardiov.ox.ac.uk).

Objectives: Our goal was to evaluate the role of myocardial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and plasma markers of oxidative stress in the pathogenesis of post-operative atrial fibrillation (AF).

Background: Atrial fibrillation is a common complication of cardiac surgery, leading to increased morbidity and prolonged hospitalization. Experimental evidence suggests that oxidative stress may be involved in the pathogenesis of AF; however, the relevance of this putative mechanism in patients undergoing cardiac surgery is unclear.

Methods: We measured basal and NADPH-stimulated superoxide production in right atrial appendage samples from 170 consecutive patients undergoing conventional coronary artery bypass surgery. Plasma markers of lipid and protein oxidation (thiorbabituric acid-reactive substances, 8-isoprostane, and protein carbonyls) were also measured in blood samples drawn from a central line before surgery and after reperfusion.

Results: Patients who developed AF after surgery (42%) were older and had a significantly increased atrial NADPH oxidase activity than patients who remained in sinus rhythm (SR) (in relative light units/s/µg protein: 4.78 ± 1.44 vs. 3.53 ± 1.04 in SR patients, p < 0.0001). Plasma markers of lipid and protein oxidation increased significantly after reperfusion; however, neither pre-operative nor post-operative measurements differed between patients who developed AF and those who remained in SR after surgery. Multivariate analysis identified atrial NADPH oxidase activity as the strongest independent predictor of post-operative AF (odds ratio 2.41; 95% confidence interval 1.71 to 3.40, p < 0.0001).

Conclusions: Atrial NADPH oxidase activity is independently associated with an increased risk of post-operative AF, suggesting that this oxidase system may be a key mediator of atrial oxidative stress leading to the development of AF after cardiac surgery.

Abbreviations and Acronyms   AERP = atrial effective refractory period   AF = atrial fibrillation   CABG = coronary artery bypass grafting   CPB = cardiopulmonary bypass   LVEF = left ventricular ejection fraction   NADPH = nicotinamide adenine dinucleotide phosphate   NO = nitric oxide   RAA = right atrial appendage   RLU = relative light units   ROS = reactive oxygen species   SR = sinus rhythm   TBARS = thiorbabituric acid-reactive substances

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