title: Mechanisms of termination and prevention of atrial fibrillation by drug therapy.
abstract: Atrial fibrillation (AF) is a disorder of the rhythm of electrical activation of the cardiac atria. It is the most common cardiac arrhythmia, has multiple aetiologies, and increases the risk of death from stroke. Pharmacological therapy is the mainstay of treatment for AF, but currently available anti-arrhythmic drugs have limited efficacy and safety. An improved understanding of how anti-arrhythmic drugs affect the electrophysiological mechanisms of AF initiation and maintenance, in the setting of the different cardiac diseases that predispose to AF, is therefore required. A variety of animal models of AF has been developed, to represent and control the pathophysiological causes and risk factors of AF, and to permit the measurement of detailed and invasive parameters relating to the associated electrophysiological mechanisms of AF. The purpose of this review is to examine, consolidate and compare available relevant data on in-vivo electrophysiological mechanisms of AF suppression by currently approved and investigational anti-arrhythmic drugs in such models. These include the Vaughan Williams class I-IV drugs, namely Na(+) channel blockers, β-adrenoceptor antagonists, action potential prolonging drugs, and Ca(2+) channel blockers; the "upstream therapies", e.g., angiotensin converting enzyme inhibitors, statins and fish oils; and a variety of investigational drugs such as "atrial-selective" multiple ion channel blockers, gap junction-enhancers, and intracellular Ca(2+)-handling modulators. It is hoped that this will help to clarify the main electrophysiological mechanisms of action of different and related drug types in different disease settings, and the likely clinical significance and potential future exploitation of such mechanisms.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. Antony.Workman@glasgow.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Workman
authors.forename: G L
authors.initials: GL
authors.lastname: Smith
authors.forename: A C
authors.initials: AC
authors.lastname: Rankin
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000145:classification / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents