title: Isoproterenol specifically modulates reverse rate-dependent effects of d,l-sotalol, d-sotalol, and dofetilide.
abstract: The modulation of antiarrhythmic and proarrhythmic properties of antiarrhythmic compounds by increased sympathetic activity is of experimental and clinical interest. However, the interaction of adrenergic stimulation with the rate-response pattern of class III antiarrhythmic agents is not well established. Using standard microelectrode techniques, we evaluated the effects of isoproterenol (iso) on the action of d,l-sotalol (d,l-sot), d-sotalol (d-sot), and dofetilide (dof) on action-potential parameters recorded from isolated canine cardiomyocytes. The cell-isolation procedure was performed from the endocardial layers of left ventricular myocardium from healthy beagle dogs. The following electrophysiologic parameters were recorded: resting membrane potential (RMP), action-potential amplitude (APA), action-potential duration at 90% repolarization (APD 90), and effective refractory period (ERP). After exposure to iso, the class III activity of d,l-sot was well maintained over the entire range of frequencies studied. In contrast, iso differentially antagonized the action of d-sot and dof. In comparison to dof, the class III action of d-sot was particularly sensitive to iso, predominantly at faster stimulation rates. Our observations demonstrate specific rate regulation of the class III action of d,l-sot, d-sot, and dof in response to adrenergic stimulation. The unfavorable rate-response pattern of d-sot compared with d,l-sot and dof might prove disadvantageous in high-catecholamine states.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Marschang
authors.forename: J
authors.initials: J
authors.lastname: Brachmann
authors.forename: L
authors.initials: L
authors.lastname: Karolyi
authors.forename: W
authors.initials: W
authors.lastname: Kübler
authors.forename: W
authors.initials: W
authors.lastname: Schöls
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010627:Phenethylamines / Q000037:antagonists & inhibitors*; D013015:Sotalol / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000037:antagonists & inhibitors*
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D010627:Phenethylamines; D013449:Sulfonamides; D013015:Sotalol; D007545:Isoproterenol; C063533:dofetilide