New Directions in the Development of Antiarrhythmic Drugs

To identify new antiarrhythmic drugs and their mechanisms of actions, it has been necessary to use appropriate models to describe arrhythmias. Recently introduced concepts in cellular electrophysiology of arrhythmias provide the newest models in which drug development have been attempted. Arrhythmias have been attributed to abnormalities of conduction, abnormalities of impulse formation, or a combination of both. Recent descriptions of abnormally triggered rhythms have been ascribed to a phenomenon called afterdepolarizations. An ionic basis for the formation of these arrhythmias has been recently described. Further, specificity of the drug effects at a cellular level to modify these arrhythmias are being observed by a variety of new techniques. Microelectrode methods have provided direct access to the intracellular milieu to determine the biophysical changes brought about by antiarrhythmic agents. These observations have led to a greater understanding of the underlying abnormalities at the cellular level. Testing of antiarrhythmic drugs in the intact heart has led to the development of clinical use of invasive electrophysiologic techniques. Intracardiac catheters are being used to describe abnormalities of impulse initiation as well as conduction. Efficacy of antiarrhythmic drugs in the intact heart may be determined with greater accuracy using these techniques. Abnormal rhythms can be initiated and terminated using intracardiac catheter methods with antiarrhythmic agents as therapeutic adjuncts.