Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs

Abstract

The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity in the action potential waveform reflects the difference in the repolarizing potassium channel currents involved. The diastolic depolarization, the trigger of automatic action potentials, is caused by multiple membrane currents, including the Na+-Ca2+ exchanger current and late INa. The action potential waveform and automaticity are affected differentially by α- and β-adrenoceptor stimulation. Class I antiarrhythmic drugs block the propagation of ectopic electrical activity of the pulmonary vein myocardium through blockade of the peak INa. Some of the class I antiarrhythmic drugs block the late INa and inhibit pulmonary vein automaticity. The negative inotropic and chronotropic effects of class I antiarrhythmic drugs could be largely attributed to their blocking effect on the Ca2+ channel rather than the Na+ channel. Such a comprehensive understanding of pulmonary vein automaticity and class I antiarrhythmic drugs would lead to an improvement in pharmacotherapy and the development of novel therapeutic agents for atrial fibrillation.