Kim Young M, Kattach Hassan, Ratnatunga Chandi, Pillai Ravi, Channon Keith M, Casadei Barbara
University Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
J Am Coll Cardiol. 2008 Jan 1;51(1):68-74. doi: 10.1016/j.jacc.2007.07.085.
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).
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.
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.
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/mug 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).
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.
我们的目标是评估心肌烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性及氧化应激血浆标志物在术后心房颤动（AF）发病机制中的作用。
心房颤动是心脏手术常见的并发症，会导致发病率增加及住院时间延长。实验证据表明氧化应激可能参与房颤的发病机制；然而，这种假定机制在接受心脏手术患者中的相关性尚不清楚。
我们测量了170例连续接受传统冠状动脉搭桥手术患者右心耳样本中基础及NADPH刺激后的超氧化物生成量。还在术前及再灌注后从中心静脉导管采集的血样中测量了脂质和蛋白质氧化的血浆标志物（硫代巴比妥酸反应性物质、8-异前列腺素和蛋白质羰基）。
术后发生房颤的患者（42%）年龄较大，心房NADPH氧化酶活性显著高于维持窦性心律（SR）的患者（相对光单位/秒/微克蛋白质：房颤患者为4.78±1.44，SR患者为3.53±1.04，p<0.0001）。再灌注后脂质和蛋白质氧化的血浆标志物显著增加；然而，术后发生房颤的患者与术后维持SR的患者术前及术后测量值均无差异。多变量分析确定心房NADPH氧化酶活性是术后房颤最强的独立预测因素（比值比2.41；95%置信区间1.71至3.40，p<0.0001）。
心房NADPH氧化酶活性与术后房颤风险增加独立相关，提示该氧化酶系统可能是导致心脏手术后房颤发生的心房氧化应激的关键介质。
