Background-The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome. Methods and Results-Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural ECG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 mol/L), a K ϩ channel opener, or the combination of a Na ϩ channel blocker (flecainide, 7 mol/L) and acetylcholine (ACh, 2 to 3 mol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 mol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole, which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF). Transient outward current (I to ) block with 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 mol/L) restored the dome, normalized the ST segment, and prevented VT/VF. Conclusions-Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to I to block (4-aminopyridine, quinidine) as an effective pharmacological treatment. (Circulation. 1999;100:1660-1666.)

Our results provide the first direct evidence that opposing voltage gradients between epicardium and the M region and endocardium and the M region contribute prominently to the inscription of the ECG T wave under normal conditions and to the widened or bifurcated T wave and long-QT interval observed under LQT conditions. Our data suggest that the "pathophysiological U" wave observed in acquired or congenital LQTS is more likely to be a second component of an interrupted T wave, and argue for use of the term T2 in place of U to describe this event.

Our results provide the first direct evidence in support of the hypothesis that heterogeneous distribution of a transient outward current-mediated spike-and-dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. The presence of a prominent action potential notch in epicardium but not endocardium is shown to provide a voltage gradient that manifests as a J (Osborn) wave or elevated J-point in the ECG.

The J wave, also referred to as an Osborn wave, is a deflection immediately following the QRS complex of the surface ECG. When partially buried in the R wave, the J wave appears as a J point elevation or ST segment elevation. Several lines of evidence have been advanced suggesting that arrhythmias associated with early repolarization (ER) pattern in the inferior leads or mid- to lateral precordial leads, Brugada syndrome (BrS) as well arrhythmias associated with hypothermia and the acute phase of ST segment elevation myocardial infarction (STEMI), are mechanistically linked to abnormalities in the manifestation of the transient outward current (Ito)-mediated J wave. Although BrS and early repolarization syndrome (ERS) differ with respect to the magnitude and lead location of abnormal J wave manifestation, they can be considered to represent a continuous spectrum of phenotypic expression that we propose be termed J wave syndromes. This review attempts to summarize our current state of knowledge concerning J-wave syndromes, bridging basic and clinical aspects. We propose to divide ERS into three subtypes: Type 1, displaying an ER pattern predominantly in the lateral precordial leads, is prevalent among healthy male athletes and rarely seen in VF survivors; Type 2, displaying an ER pattern predominantly in the inferior or infero-lateral leads, is associated with a higher level of risk; whereas Type 3, displaying an ER pattern globally in the inferior, lateral and right precordial leads, is associated with the highest level of risk for development of malignant arrhythmias and is often associated with VF storms.