Ionic remodeling in the heart: pathophysiological significance and new therapeutic opportunities for atrial fibrillation.

Heart disease has long been recognized to alter cardiac electrical function. Detailed studies of disease-induced remodeling of ionic transport processes that underlie ventricular electrophysiological alterations have been performed over the past 10 years, but our knowledge of atrial ionic remodeling is more limited and has emerged much more recently. The present review focuses on recent findings regarding ionic remodeling at the atrial level, particularly with respect to two conditions that promote atrial fibrillation (AF) in well-developed clinically relevant animal models: (1) sustained atrial tachycardia and (2) ventricular tachypacing-induced congestive heart failure. Complementary data from experimental models and from observations in atrial tissue samples from patients are examined critically and integrated. Consideration is also given to potential molecular mechanisms underlying remodeling, the relationship between atrial and ventricular ionic remodeling in response to similar stimuli, and the potential relevance of insights into ionic remodeling for understanding the pathophysiology of AF and developing improved therapeutic approaches.