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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)
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)
The role of electrical heterogeneity in development of cardiac arrhythmias is well recognized. The extent to which transmembrane action potential (TAP) heterogeneity contributes to the normal electrophysiology of well-oxygenated atria is not well defined. The principal objective of the present study was to define regional and transmural differences in(More)
BACKGROUND Mutations in the ryanodine 2 receptor (RyR2) gene have been identified in patients with catecholaminergic polymorphic ventricular tachycardia. We examined the cellular basis for the ECG features and arrhythmia mechanisms using low-dose caffeine to mimic the defective calcium homeostasis encountered under these conditions. METHODS AND RESULTS A(More)
BACKGROUND Amiodarone and ranolazine have been characterized as inactivated- and activated-state blockers of cardiac sodium channel current (I(Na)), respectively, and shown to cause atrial-selective depression of I(Na)-related parameters. This study tests the hypothesis that their combined actions synergistically depress I(Na)-dependent parameters in atria(More)
BACKGROUND The arrhythmogenic effects of hyperthermia have been highlighted in the Brugada syndrome but remain largely unexplored in other arrhythmic syndromes. The present study examines the effect of hyperthermia on transmural dispersion of action potential duration (TD-APD), early afterdepolarization (EAD) activity, and torsade de pointes (TdP) under(More)
BACKGROUND Several clinical trials have shown that vernakalant is effective in terminating recent onset atrial fibrillation (AF). The electrophysiological actions of vernakalant are not fully understood. METHODS AND RESULTS Here we report the results of a blinded study comparing the in vitro canine atrial electrophysiological effects of vernakalant,(More)
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