My primary interest currently is to define the extent to which atrial and ventricular tissues differ in their electrophysiological characteristics and pharmacological response to sodium channel blockers. Our goal is to identify atrial selective sodium channel blockers that may be useful in the management of atrial fibrillation. Among the current strategies for suppressing atrial fibrillation is the development of antiarrhythmic agents that selectively affect atrial electrical parameters. The need for these novel strategies stems from the pro-arrhythmic effect of currently available drugs on the ventricular myocardium. We have recently identified a major atrioventricular distinction in biophysical properties of the sodium channel and a pharmacological agent, ranolazine, which is able to exploit these differences. Ranolazine suppresses sodium channel current–dependent parameters in an atrial selective manner and effectively suppresses atrial fibrillation. Our pilot studies suggest that there are atrial-selective, atrial-predominant, as well as non-selective sodium channel blockers. Investigations into the molecular basis and biophysical mechanisms underlying atrial selectivity of sodium channel blockers are underway.

Burashnikov A, Antzelevitch C. Acceleration-induced action potential prolongation and early afterdepolarizations. J.Cardiovascular. Electophysiol. 1998;9:934-948.
PubMed ID: 9786074

Burashnikov A, Antzelevitch C. Differences in response of four ventricular cell types to alpha 1-adrenergic agonists. Cardiovasc. Res. 1999;43:901-908
PubMed ID: 10615417

Burashnikov A, Antzelevitch C. Block of IKs does not induce early afterdepolarization activity but promotes b-adrenergic agonist-induced delayed afterdepolarization activity in canine ventricular myocardium. J. Cardiovascular Electrophysiology, 2000;11:458-465.
PubMed ID: 10809500

Burashnikov A, Antzelevitch C. A prominent IKs in epicardium and endocardium contributes to the development of transmural dispersion of repolarization but protects against the development of early afterdepolarization. J. Cardiovascular Electrophysiology, 2002;13:172-177.
PubMed ID: 11900293

Burashnikov A, Antzelevitch A. Re-induction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity. Circulation, 2003;107:2355-2360.
PubMed ID: 12695296

Burashnikov A, Mannava S, Antzelevitch C. Transmembrane Action Potential Heterogeneity in the Canine Isolated Arterially-perfused Right Atrium: Effect of IKr and IKur/Ito block. Am.J.Physiol., 2004;286:H2393-H9400.
PubMed ID: 15148061

Antzelevitch C, Belardinelli L, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Cordeiro JM, Thomas G. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation, 2004;110:904-910.
PubMed ID: 15302796

Burashnikov A, Antzelevitch C. Role repolarization restitution in the development of coarse and fine atrial fibrillation in the isolated canine right atria. J. Cardiovascular Electrophysiology, 2005;16:639-645
PubMed ID: 15946365

Burashnikov A, Antzelevitch C. Late phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation. PACE, 2006;29:290-295.
PubMed ID: 16606397

Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block as a strategy for suppression of atrial fibrillation. Differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation, 2007;116:1449-1457. PubMed ID: 17785620