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BACKGROUND Ranolazine is a novel antianginal agent capable of producing antiischemic effects at plasma concentrations of 2 to 6 micromol/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. (More)
Ranolazine is a novel antianginal agent capable of producing anti-ischemic effects at plasma concentrations of 2 to 6 microM without a significant reduction of heart rate or blood pressure. This review summarizes the electrophysiologic properties of ranolazine. Ranolazine significantly blocks I(Kr) (IC(50) = 12 microM), late I(Na), late I(Ca), peak I(Ca),(More)
The discovery and characterization of the M cell, a unique cell type residing in the deep layers of the ventricular myocardium, has opened a new door in our understanding of the electrophysiology and pharmacology of the heart in both health and disease. The hallmark of the M cell is the ability of its action potential to prolong much more than that of other(More)
INTRODUCTION Precipitation of torsades de pointes (TdP) has been shown to be associated with acceleration of heart rate in both experimental and clinical studies. To gain insight into the cellular mechanism(s) responsible for the initiation of acceleration-induced TdP, we studied the effect of acceleration of pacing rate in canine left ventricular(More)
BACKGROUND Dronedarone is approved by the U.S. Food and Drug Administration for the treatment of patients with atrial fibrillation (AF) as a safe alternative to amiodarone. There are no full-length published reports describing the effectiveness of acute dronedarone use against AF in experimental or clinical studies. OBJECTIVE The purpose of this study was(More)
BACKGROUND Atrial fibrillation (AF) at times recurs immediately after termination of the arrhythmia. The mechanism(s) responsible for the extrasystole that reinduces AF is largely unknown. We hypothesized that abbreviation of action potential duration (APD) would permit very rapid rates of excitation, known to induce intracellular calcium loading, which in(More)
Ranolazine is a Food and Drug Administration-approved antianginal agent. Experimental and clinical studies have shown that ranolazine has antiarrhythmic effects in both ventricles and atria. In the ventricles, ranolazine can suppress arrhythmias associated with acute coronary syndrome, long QT syndrome, heart failure, ischemia, and reperfusion. In atria,(More)
Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Currently available antiarrhythmic drugs (AADs), although highly effective in acute cardioversion of paroxysmal AF, are generally only moderately successful in long-term maintenance of sinus rhythm. The use of AADs is often associated with an increased(More)
BACKGROUND The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF). METHODS AND RESULTS Whole-cell patch clamp techniques were used to evaluate inactivation of peak sodium channel current (I(Na)) in myocytes isolated from canine atria and ventricles. The electrophysiological effects of(More)