Fibrilación auricular. Un enfoque radical.

Dra. Barbara Casadei
John Radcliffe Hospital. Oxford.
15st of May of 2009

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans and is characterized by the ability to self perpetuate due to a number of changes in the electrical and structural properties of the atrial myocardium. Although the process of AF-induced remodeling and its role in “begetting” AF have been described in great detail in animal models of atrial tachyarrhythmias and in human AF, the molecular processes underlying these changes remain unclear.
Over the last few years, our work and that of others has suggested that altered nitric oxide-redox equilibrium of the atrial myocardium may play an important part both in promoting the new onset of AF and in inducing electrophysiological remodelling. In humans, an increasing body of evidence indicates that formation of superoxide by NADPH oxidases plays a critical role in the development of a wide range of cardiovascular diseases suggesting that this oxidase system may also be an important source of reactive oxygen species in the fibrillating human atrial myocardium. We have recently reported that (i) a membrane-bound gp91phox/NOX2 containing NADPH oxidase is the main source of superoxide production in human atrial myocytes obtained from the right atrial appendage of patients undergoing coronary artery bypass surgery; (ii) atrial NADPH oxidase-dependent superoxide production is significantly increased in patients with paroxysmal or persistent AF compared with matched controls in sinus rhythm; (iii) myocardial NADPH oxidase activity is a positive independent predictor of the occurrence of postoperative AF in patients undergoing CABG surgery. These findings suggest that NADPH oxidases may be a potential novel therapeutic target in AF.

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Key References

Kim YM, Guzik TJ, Zhang YH, et al. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res 2005;97:629-36.

Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol 2008;51:68-74.