MECHANISMS OF ATRIAL-FIBRILLATION AND ACTION OF DRUGS USED IN ITS MANAGEMENT

Drugs remain the mainstay of treatment of patients with atrial fibrill ation (AF), An understanding of the mechanisms of AF and of atrioventr icular (AV) conduction provides a basis for the understanding of the m echanisms of antiarrhythmic drug action. Although ectopic activity fro m a focus may initiate AF, re-entry is the usual mechanism of maintena nce. In its classical form, reentry takes the form of circus movements around fixed anatomic structures. However, leading circle and anisotr opic variants of reentry may arise as a result of functional variation s of refractoriness or anistropic conduction. Electrical remodeling du ring AF favors its persistence. Reentry may be prevented by prolongati on of the refractory period. Class III antiarrhythmic drugs prolong re fractoriness by blockade of outward potassium currents. Class I drugs prolong refractoriness by delaying the recovery of of the sodium curre nt. Many class I drugs also have potassium channel-blocking action. In AF the rate of conduction of rapid impulses to the ventricle is contr olled by conduction over the AV node. Blockade of the L-type calcium c hannels, activation of the muscarinic and adenosine A(1) receptors, or beta-adrenergic blockade will slow conduction over the AV node. The a dverse cardiovascular effects of drugs used to treat AF can be predict ed on the basis of their mechanisms of action. The current focus of dr ug development is on specific potassium channel blockers. (C)1998 by E xcerpta Medica, Inc.