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 μmol/L), a K+ channel opener, or the combination of a Na+ channel blocker (flecainide, 7 μmol/L) and acetylcholine (ACh, 2 to 3 μmol/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 μmol/L) restored the epicardial dome, thus reducing...

Cellular Basis for the Brugada Syndrome and Other Mechanisms of Arrhythmogenesis Associated With ST-Segment Elevation

—The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-...

Ionic Mechanisms Responsible for the Electrocardiographic Phenotype of the Brugada Syndrome Are Temperature Dependent

J-Point Elevation in Survivors of Primary Ventricular Fibrillation and Matched Control Subjects: Incidence and Clinical Significance

https://www.heartrhythmjournal.com/article/S1547-5271(09)01377-0/pdf

J Wave Syndromes

Cardiac K+ channels are membrane-spanning proteins that allow the passive movement of K+ ions across the cell membrane along its electrochemical gradient. They regulate the resting membrane potential, the frequency of pacemaker cells and the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters and hormones and class III antiarrhythmic drugs that prolong the action potential duration (APD) and refractoriness and have been found effective to prevent/suppress cardiac arrhythmias. In the human heart, K+ channels include voltage-gated channels, such as the rapidly activating and inactivating transient outward current (Ito1), the ultrarapid (IKur), rapid (IKr) and slow (IKs) components of the delayed rectifier current and the inward rectifier current (IK1), the ligand-gated channels, including the adenosine triphosphate-sensitive (IKATP) and the acetylcholine-activated (IKAch) currents and the leak channels. Changes in the expression of K+ channels explain the regional variations in the morphology and duration of the cardiac action potential among different cardiac regions and are influenced by heart rate, intracellular signalling pathways, drugs and cardiovascular disorders. A progressive number of cardiac and noncardiac drugs block cardiac K+ channels and can cause a marked prolongation of the action potential duration (i.e. an acquired long QT syndrome, LQTS) and a distinct polymorphic ventricular tachycardia termed torsades de pointes. In addition, mutations in the genes encoding IKr (KCNH2/KCNE2) and IKs (KCNQ1/KCNE1) channels have been identified in some types of the congenital long QT syndrome. This review concentrates on the function, molecular determinants, regulation and, particularly, on the mechanism of action of drugs modulating the K+ channels present in the sarcolemma of human cardiac myocytes that contribute to the different phases of the cardiac action potential under physiological and pathological conditions.

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Pharmacology of cardiac potassium channels

Background The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R′). Also referred to as an Osborn wave, the J wave has been observed in the ECG of animals and humans for more than four decades, yet the mechanism underlying its manifestation is poorly understood. The present study investigates the cellular basis for the J wave using an isolated arterially perfused preparation consisting of a wedge of canine right or left ventricle. Methods and Results A 12-lead ECG was initially recorded in vivo. After isolation and arterial perfusion of the right or left ventricular wedge, transmembrane action potentials were simultaneously recorded from epicardial, M region, and endocardial transmural sites with three floating microelectrodes. A transmural ECG was recorded concurrently. A J wave was observed at the R-ST junction of the ECG in 17 of 20 adult dogs, usually in leads II, III, aVR, and aVF and the mid to lateral precordial leads. The J wave...

CharlesAntzelevitch

Papers

Cellular Basis for the Electrocardiographic J Wave