Tracing the origins of postoperative atrial fibrillation: the concept of oxidative stress-mediated myocardial injury phenomenon

Abstract

Atrial fibrillation (AF) is the most common arrhythmia associated with coronary artery surgery and is an important factor contributing to postoperative morbidity and mortality. Recently, there is growing evidence that dysregulation of the oxidant-antioxidant balance, inflammatory factors and discordant alteration of energy metabolites may play a significant role in its pathogenesis. We evaluated the link between postoperative atrial fibrillation with inflammatory factors and oxidative stress. We searched all databases in Medline, Pubmed, ISI, the Cochrane database, and Embase. We identified more than 100 trials, multiple metaanalyses, and three sets of practice guidelines for the prevention of PAF in cardiac surgery. Mechanisms of postoperative AF are likely to be multifactorial and are influenced by preoperative, intraoperative and postoperative factors including a genetic basis. Electrical remodelling is thought to be related to the generation of reactive oxidant species and inflammatory factors during the ischemia-reperfusion phase of cardiac surgery. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was found to be the primary source of superoxide within the human atrial myocardium (in patients in sinus rhythm and in those with AF) and linked with paroxysmal and chronic AF. Reactive oxidant species cause lipid peroxidation, breakdown of cell membrane, decreased mitochondrial function, calcium overload and apoptosis. This affect was shown to be reversed by exogenous nitric oxide/donors (sodium nitroprusside). Inflammatory factors such as the rise in white blood cell count, C-reactive proteins were implicated in the pathogenesis of AF. In contrast, new evidence identifies statins as having both antioxidant and anti-inflammatory properties and that their use reduces the incidence of postoperative AF (57% in the control vs. 35% in the atorvastatin group). Other antiinflammatory strategies include steroids with one study showing postoperative AF occurred in 21% in the steroid group compared with 51% in the placebo group although their use resulted in an increase in other complications. The mainstay of therapy however, remains to be beta-blockers alone which impart a modest influence on overall rates of AF with a reduction from 33.7 to 16.9% (OR: 0.37, 95% CI: 0.29-0.48). Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers has been shown in one study to reduce the risk of developing new-onset AF by nearly 50%, although this has not been adequately evaluated in cardiac surgery. Inflammatory factors and oxidative stress play a major role in the pathogenesis of postoperative AF. This review provides an analysis of current evidence in support of efforts directed at antiinflammatory and antioxidant agents as interventions.