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.