Basic cardiac electrophysiology and mechanisms of antiarrhythmic agents

Basic cardiac electrophysiology and how it applies to antiarrhythmic drug therapy are reviewed. Normal impulse propagation through the heart proceeds in sequence from the sinoatrial (SA) node, through the atrial specialized conducting system, the atrioventricular (AV) node, the His-Pur-kinje system, and into the ventricles. The cardiac cell maintains a resting membrane potential until an electrical stimulus depolarizes the cell and generates an action potential. The action potential is composed of five phases that represent the changing ionic fluxes and membrane potentials of the cardiac cell. The heart contains two types of cardiac conducting fibers. The fast- and slow-current action potentials generated by these fiber types exhibit distinctly different electrophysiologic properties. Cardiac arrhythmias generally result from an abnormality in the rate, rhythm, or conduction of an electrical impulse in the heart. They may be described as disturbances in normal impulse initiation (automaticity), impulse conduction, or both. Various portions of the conduction system are under the control of the autonomic nervous system, which depends on the balance between the activity of the parasympathetic and sympathetic nervous systems. Intracellular and extracellular concentrations of potassium, calcium, and magnesium have important effects on the electrophysiology of the heart. These changes can be critical in the production of various arrhythmias or may affect the efficacy or toxicity of various antiarrhythmic agents. The electrophysiology of quinidine, procainamide, disopyramide, lidocaine, tocainide, phenytoin, flecainide, amiodarone, and bretylium tosylate is discussed to detail the relationship between drug action and antiarrhythmic efficacy. The electrophysiologic effects of beta-blocking agents and calcium-channel antagonists are also presented. This basic primer on cardiac electrophysiology should provide the practitioner with an improved understanding of the effects, indications, and limitations of antiarrhythmic drugs.