The gain-of-function Scn5a+/IKPQ mutation in the cardiac Na+ channel causes human long QT type 3 syndrome (LQT3) associated with ventricular arrhythmogenesis. The KATP channel-opener nicorandil (20uM) significantly reduced arrhythmic incidence in Langendorff-perfused Scn5a+/I hearts during programmed electrical stimulation; wild-types (WTs) showed a total absence of arrhythmogenicity. These observations precisely correlated with alterations in recently established criteria for re-entrant excitation reflected in: (1) shortened left-ventricular epicardial but not endocardial monophasic action potential durations at 90% repolarization (APD90) that restored transmural repolarization gradients, IAPD90. Scn5a+/I hearts showed longer epicardial but not endocardial APD90s, giving shorter IAPD90s than WT hearts. Nicorandil reduced.
Increasing evidence indicates that congenital long QT syndromes (LQTSs) promote atrial fibrillation. The atrial action potential (AP) has a short plateau, and whether LQTS atrial cardiomyocytes generate triggered activity via early afterdepolarizations (EADs) is unclear. Atrial cellular arrhythmi...
Ventricular tachycardia (VT) in Brugada Syndrome patients often originates in the right ventricular outflow tract (RVOT). We explore the physiological basis for this observation using murine whole heart preparations. Ventricular bipolar electrograms and monophasic action potentials were recorded ...
Mutations in the cardiac ryanodine receptor gene (RyR2) have been recently identified in victims of sudden infant death syndrome. The aim of this study was to determine whether a gain-of-function mutation in RyR2 increases the propensity to cardiac arrhythmias and sudden death in young mice. s an...
Two major mechanisms have been postulated for the arrhythmogenic tendency observed in Brugada Syndrome (BrS): delays in conduction or increased heterogeneities in repolarization. We use a contact mapping system to directly investigate the interacting roles of these two mechanisms in arrhythmogene...
The aim of the present study was to identify specific electrocardiogram (ECG) features that predict the development of multiple episodes of ventricular fibrillation (VF) in patients with an early repolarization (ER) pattern and to compare the mode of VF initiation with that observed in typical ca...
Computer modelling has emerged as a particularly useful tool in understanding the physiology and pathophysiology of cardiac tissues. Models of ventricular, atrial and nodal tissue have evolved and include detailed ion channel kinetics and intercellular Ca2+ handling. Purkinje fibre cells play a c...
We investigate the extent to which the electrocardiographic (ECG) properties of intact Scn5a+/- mice reproduce the corresponding clinical Brugada syndrome phenotype and use this model to investigate the role of conduction and repolarization abnormalities in the arrhythmogenic mechanism.Methods an...
Brugada syndrome is an arrhythmogenic disease characterized by a pattern of ST segment elevation in the right precordial leads on an electrocardiogram with an increased risk of sudden cardiac death. It is primarily reported in adults with limited data about the prevalence, prognosis, and long-ter...
Used a murine model of arrhythmogenic right ventricular cardiomyopathy (ARVC) to test whether reducing ventricular load prevents or slows development of this cardiomyopathy. At present, no therapy exists to slow progression of ARVC. Genetically conferred dysfunction of the mechanical cell–ce...
Since the discovery of the genetic bases of the long QT syndrome, several new genetically mediated arrhythmias have been described, defining a new group of syndromes, called inherited arrhythmogenic diseases. This allowed clarifying the substrate of several cases of juvenile sudden death, previou...
