Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2.

Background: Ranolazine (Ran) is known to inhibit multiple targets, including the late Na(+)current, the rapid delayed rectifying K(+)current, the L-type Ca(2+)current, and fatty acid metabolism. Functionally, Ran suppresses early afterdepolarization (EADs) and torsades de pointes (TdP) in drug-induced long QT type 2 (LQT2) presumably by decreasing intracellular [Na(+)](i) and Ca(2+)overload. However, simulations of EADs in LQT2 failed to predict their suppression by Ran.

Increase in organization index predicts atrial fibrillation termination with flecainide post-ablation: spectral analysis of intracardiac electrograms.

Aims: The mechanism of the action of flecainide in the termination of human atrial fibrillation (AF) is not fully understood. We studied the acute effects of flecainide on AF electrograms in the time and frequency domain to identify factors associated with AF termination.

Methods And Results: Patients who were still in AF at the end of catheter ablation for AF were given intravenous flecainide.

Pulmonary Vein Isolation using a High Density Mesh Ablator Catheter: Incorporation of three-Dimensional Navigation and Mappin.

We evaluated the use of a novel High Density Mesh Ablator (HDMA) catheter in combination with three-dimensional navigation for the treatment of paroxysmal atrial fibrillation. The HDMA catheter was used to carry out pulmonary vein isolation in a consecutive series of patients. Three-dimensional geometry of the left atrial-pulmonary vein (LA-PV) junctions were first created with the HDMA catheter.

Sympathetic nerve stimulation produces spatial heterogeneities of action potential restitution.

Background: Restitution kinetics (RK) of action potential duration (APD) are classically studied by applying an extra impulse at varying diastolic intervals (DI) and might differ from RK elicited by sympathetic nerve stimulation (SNRK).

Objective: To measure 'Physiological' RK during gradual increases in heart rate caused by sympathetic nerve stimulation (SNS) and its possible spatial heterogeneities caused by non-uniform innervation of the myocardium.

Methods: The SNRK was measured from rabbit hearts with intact sympathetic innervation using optical mapping.

Autonomic nerve stimulation reverses ventricular repolarization sequence in rabbit hearts.

Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. Rabbit hearts were perfused in a Langendorff apparatus with full sympathetic and parasympathetic innervation and were optically mapped to measure action potential durations and DOR (apex-base) over the left ventricles. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 micromol/L) infusion.