Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs.
The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly 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 that cause proarrhythmic reactions to antiarrhythmic drugs. The present article reviews the experimental evidence that has been obtained regarding the mechanisms of proarrhythmia. The evidence available provides important insights, and points to potential strategies for developing newer and safer antiarrhythmic compounds.
Nattel
S
S
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
D000200:Action Potentials; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism; D004562:Electrocardiography; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers