The Assessment of Oxidative Stress Markers and the Development of Atrial Fibrillation After Cardiac Surgery

Atrial Fibrillation (AF) is a common occurrence after cardiac surgery. This arrhythmia is reported to occur in up to 40% of patients following coronary bypass graft (CABG) surgery. The incidence of AF is even higher in patients who have undergone both CABG and valvular surgery during the same operation. In cardiac surgery patients, the occurrence of atrial fibrillation post-operatively lengthens hospitalization and adds to postoperative complications like renal dysfunction, infection, and cognitive defects. Postoperative AF is a known major risk factor for the development of stroke after cardiac surgery. Additionally, there is data to suggest that the development of AF after cardiac surgery is related to both reduced survival after CABG, and this dysrhythmia may also serve as an independent predictor of long-term mortality. Many studies have investigated the role of prophylactic pharmacological therapy to prevent post-operative AF after cardiac surgery. Despite this, the complete pathogenesis of AF in the post-cardiac surgery population remains unknown, is likely to be multifactorial, and includes clinical, structural, and biochemical risk factors.

Biochemical risk factors such as inflammation and elevated markers of oxidative stress seem to be related to the development of AF. Also, It has been shown that AF is associated with decreased activity of nitric oxide synthases. Elevated C-reactive protein (CRP), a common marker of inflammation, has been shown to be associated with chronic AF at one year follow up. Additionally, elevated CRP levels drawn just prior to electrical cardioversion have been found to predict the development of recurrent AF after cardioversion. This relationship between this elevated marker of inflammation - CRP - and AF has been found to be independent of clinical risk factors for the development of AF, such as age, diabetes, and left ventricular function. Inflammation is a known source of oxidative stress at the cellular level; and it has been proposed that both inflammation and oxidative stress play a role in electrical remodeling of the atria, which promotes perpetuation of AF. Moreover, it has been proposed that CRP levels may directly reflect the condition of increased oxidative stress.

Oxidative Stress and Arrhythmia:

The association between AF and arrhythmias has been suggested by an array of evidence. Moreover, the pathogenesis likely involves both changes in the atrial architecture, such as dilation and fibrosis, and alterations in the electrophysiological substrate of atrial tissue. Oxidative stress markers are believed to be involved in remodeling of the atrial electrophysiological substrate.

Recently, a correlation between AF and oxidative stress markers has been established. In one study, a correlation between the oxidative stress markers reduced glutathione, cysteine, and derivatives of reduced oxidative metabolites has been found. Although the relationship between AF and oxidative stress remains unclear, it is known from this human population study that oxidative stress markers are elevated in those with persistent AF. This relationship holds true even after controlling for conditions that promote oxidative stress: hypertension, smoking, and congestive heart failure. It has also been shown that atrial tachycardias are associated with increased hydroxyl radicals and peroxynitrite. These species are believed to cause myofibril damage and reduced myofibrillar creatine kinase activity in those with chronic AF. Similarly, superoxide free radicals were shown to be elevated in the porcine heart left atrial appendage when subjected to rapid atrial pacing and AF. Of further interest in this study by Dudley et al., was the role of an NADPH oxidase inhibitor, apocynin, in its ability to reduce superoxide production. This suggests that the NADPH oxidase plays a prominent role in the development of reactive oxidative species. In turn, such reactive oxidative species are thought to be related to inflammation and atrial electrical remodeling.