Amiloride. Antiarrhythmic and electrophysiological activity in the dog

Amiloride, a widely used diuretic, has multiple pharmacological actions, including inhibition of the sodium-hydronium ion and the sodium-calcium exchanger in heart. In terms of cardiac electrophysiology, amiloride prolongs action potential duration without alteration in upstroke velocity of phase 0 in Purkinje fibers. The antiarrhythmic efficacy of amiloride was assessed in a model of inducible sustained ventricular tachyarrhythmias in 16 dogs late after 2-hour occlusion-reperfusion of the left anterior descending coronary artery. Sixteen animals were studied: Four were randomly assigned to placebo, and 12 were assigned to amiloride treatment. Prolonged loading and maintenance infusions were designed to produce amiloride concentrations over the range achievable in humans. Animals were chronically instrumented to allow electrophysiological measures of conduction and refractoriness in the left ventricular infarct and border zones. Of the 12 animals treated with amiloride, six responded with inability to induce ventricular tachyarrhythmias, whereas of the four animals treated with placebo, none responded. The mean infarct size of the six animals responding to amiloride (12 +/- 5%) was significantly less than that of the six animals not responding to amiloride (20 +/- 8%). Overall, the only electrophysiological effect of amiloride observed in this study was prolongation of border zone ventricular refractoriness. This electrophysiological effect was accentuated in animals responding to amiloride. In addition, when animals were subdivided into responders, partial responders, or nonresponders, the border zone repolarization time was prolonged in responders and partial responders, whereas this measure shortened in nonresponding animals. Amiloride has antiarrhythmic activity in the suppression of sustained ventricular tachyarrhythmias in this postinfarction model.