Background-Ranolazine is a novel antianginal agent capable of producing antiischemic effects at plasma concentrations of 2 to 6 mol/L without reducing heart rate or blood pressure. The present study examines its electrophysiological effects in isolated canine ventricular myocytes, tissues, and arterially perfused left ventricular wedge preparations. Methods and Results-Transmembrane action potentials (APs) from epicardial and midmyocardial (M) regions and a pseudo-ECG were recorded simultaneously from wedge preparations. APs were also recorded from epicardial and M tissues. Whole-cell currents were recorded from epicardial and M myocytes. Ranolazine inhibited I Kr (IC 50 ϭ11.5 mol/L), late I Na , late I Ca , peak I Ca , and I Na-Ca (IC 50 ϭ5.9, 50, 296, and 91 mol/L, respectively) and I Ks (17% at 30 mol/L), but caused little or no inhibition of I to or I K1 . In tissues and wedge preparations, ranolazine produced a concentration-dependent prolongation of AP duration of epicardial but abbreviation of that of M cells, leading to reduction or no change in transmural dispersion of repolarization (TDR).

2+ ihandling proteins changes identified, an enhanced I NaL seems to be a major contributor to the electrophysiological and Ca

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Our study demonstrates important differences in the inactivation characteristics of atrial versus ventricular sodium channels and a striking atrial selectivity for the action of ranolazine to produce use-dependent block of sodium channels, leading to suppression of AF. Our results point to atrium-selective sodium channel block as a novel strategy for the management of AF.

This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.