Abstract 18499: Myocardial NADPH Oxidase 2 Overexpression Increases Atrial Fibrillation Susceptibility : Inhibition by Short Term Statin Treatment
Introduction: Atrial fibrillation (AF) is associated with an increase in atrial oxidative stress. We have previously shown that a NOX2-containing NADPH oxidase (NOX2) is an important source of reactive oxygen species (ROS) in human atrial myocytes. Atrial NOX2 activity is increased early after pacing-induced AF in the goat and is an independent predictor of postoperative AF.
Hypothesis: Is an increase in atrial NOX2 activity sufficient to generate a substrate for AF?
Methods: We evaluated ECG parameters and AF inducibility (in response to burst pacing) in cardiomyocyte-specific NOX2 Tg mice. As statins inhibit NOX2 activity, we then repeated these investigations in NOX2 Tg and WT littermates that had been allocated to either atorvastatin (ATV 30 mg/kg/day) or placebo for 2 weeks. All measurements were carried out by investigators blind to genotype and treatment allocation.
Results: NOX2 Tg mice showed a modest increase in myocardial NADPH stimulated superoxide production (+16% vs. WT, n=4/group, P<0.05). There was no difference in atrial and LV size and function (by echocardiography and tissue Doppler) or collagen content. Basal ECG parameters did not differ between genotypes; however, both the probability of inducing AF (19±2.2% in Tg vs. 9±1.8% in WT, n=20/group, P<0.01) and the duration of the AF episodes were significantly increased in NOX2 Tg. Treatment with ATV abolished the difference in AF inducibility and duration between genotypes without affecting myocardial collagen content, or LV function. Neither myocardial NOX2 overexpression nor ATV treatment affected plasma or myocardial cholesterol.
Conclusions: Mild NOX2 overexpression is sufficient to increase AF susceptibility in the absence of cardiac functional or structural abnormalities. Short-term ATV treatment abolishes the difference in AF susceptibility between genotypes, independent of cholesterol lowering. These findings suggest that statin treatment may prevent the new onset of AF (particularly in the presence of increased NOX2 activity, e.g., after cardiac surgery).
Author Disclosures: A. Recale: None. R. Carnicer: None. K. Ziberna: None. J. Simon: None. S. Reilly: None. S. Verheule: None. A. Shah: None. B. Casadei: None.
- © 2014 by American Heart Association, Inc.