Relevance of cellular to clinical electrophysiology in interpreting antiarrhythmic drug action.
The usefulness of cellular electrophysiologic techniques in elucidating the fundamental actions of antiarrhythmic drugs is contrasted with their apparent lack of relevance to the selection of drugs for the treatment of particular arrhythmias. Clinical electrophysiologists employ different techniques, but their results may be explained in terms of cellular drug actions. The varying clinical effects of class IA, IB and IC agents are due to differences in the speed of their attachment to, and detachment from, sodium channels. The role of sympathetic activity in arrhythmogenesis is complex, but again readily explicable in terms of the electrophysiologic cellular actions of stimulation of the individual types of adrenoceptors (alpha 1, alpha 2, beta 1 and beta 2) and the distribution of these receptors, and of the longterm effects of sympathetic deprivation, either by antisympathetic drugs (class II) or by sympathetic denervation. Delayed repolarization (e.g., by class III drugs or prolonged beta blockade) is antiarrhythmic because it is homogeneous, despite the incidental prolongation of QT. If, however, QT is prolonged by heterogeneity of conduction or repolarization, or by partial sympathetic denervation (long QT syndrome or post myocardial infarction), this indicates increased risk of arrhythmia. Finally, the efficacy of calcium antagonists (class IV) in supraventricular arrhythmias is attributable to the cellular electrophysiologic characteristics of sinoatrial and atrioventricular nodal and transitional elements.
Vaughan Williams
E M
EM
Herford College, University of Oxford, United Kingdom.
D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000502:physiology; D006801:Humans; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D011941:Receptors, Adrenergic / Q000502:physiology; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction
D000889:Anti-Arrhythmia Agents; D011941:Receptors, Adrenergic