Electrophysiological effects of encainide (MJ9067) on canine subendocardial Purkinje fibers surviving infarction.
The electrophysiological effects of encainide (MJ9067) on canine subendocardial Purkinje fibers surviving infarction were examined 22-24 h after coronary artery ligation, using standard microelectrode techniques at pH 7.4. Encainide (5 and 10 microM) shortened APD50, decreased the action potential amplitude and overshoot, caused a 2-3 mV depolarization of the cell, and decreased the maximum rate of phase 0 depolarization. All these effects were dose dependent. APD90 was slightly, but not significantly, shortened. Encainide had a greater effect on APD50 and APD90 at longer (1,000 ms) stimulation cycle lengths than at shorter (400 ms) cycle lengths. There was a significant interaction between the effects of stimulation rate and encainide concentration on APD90, APD50, amplitude, and overshoot. The same parameters measured at a lower pH (7.1) gave similar results. There was a significant correlation (r = -0.540, p less than 0.001) between the control APD90 and the degree and direction of change of APD90 after 10 microM encainide. Automaticity of the infarcted preparations was eliminated or slowed in a dose-dependent fashion by 5 and 10 microM encainide. The curve relating membrane potential and the maximum rate of phase 0 depolarization was shifted down and toward higher potentials by 5 microM encainide. The results show that encainide produces similar changes in the action potentials of Purkinje fibers surviving infarction as in normal Purkinje fibers, and is effective in lowering the rate of spontaneous depolarization in infarcted tissue. Furthermore, encainide appears to be the only antiarrhythmic drug which has been shown to increase and decrease APD90, depending on the initial APD90 of the cell.
D000200:Action Potentials / Q000187:drug effects; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D016700:Encainide; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000187:drug effects*
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D016700:Encainide