The major limitation to antiarrhythmic drug therapy is the risk of arr
hythmia promotion, or 'proarrhythmia.' This complication may be lethal
, and greatly restricts the value of antiarrhythmic agents, particular
ly for arrhythmias without an intrinsic mortality risk, such as atrial
fibrillation. In order for improved antiarrhythmic drug therapy to be
developed, it is essential to understand the fundamental mechanisms t
hat cause proarrhythmic reactions to antiarrhythmic drugs. The present
article reviews the experimental evidence that has been obtained rega
rding the mechanisms of proarrhythmia. The evidence available provides
important insights, and points to potential strategies for developing
newer and safer antiarrhythmic compounds. (C) 1998 Elsevier Science B
.V.