Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues.
The intracellular electrophysiological properties of a new, orally effective antiarrhythmic agent, indecainide hydrochloride, were studied in isolated canine myocardial preparations stimulated at 1 Hz and superfused with Tyrode's solution. In Purkinje fibers, indecainide (10(-6) and 3 X 10(-6) M) decreased the maximal rate of rise of phase 0 (Vmax), conduction velocity, action potential duration APD, and effective refractory period, and shifted the membrane response curve by 5 mV in a hyperpolarizing direction. In papillary muscle, APD was unchanged, but Vmax was decreased. The effect of the drug on Vmax was rate dependent, but over physiologically relevant cycle lengths (370 to 1,000 ms), Vmax remained relatively constant. In the presence of indecainide (3 X 10(-6) M) and at a basic cycle length of 333 ms, the rate constant for block onset was 0.06 and 0.1 action potentials-1 in Purkinje fiber and papillary muscle, respectively. The recovery of Vmax from maximum steady-state block was half completed in Purkinje fibers and muscle in 52 and 49 s, respectively. No resting block was apparent in either tissue at normal resting membrane potential. Indecainide had only minimal effects on automaticity arising from normal or depolarized (barium) membrane potentials. Thus, indecainide is a potent class I local anesthetic antiarrhythmic agent that depresses Vmax and conduction in cardiac tissues. The depressant effects of indecainide are completely dependent on prior activation of the tissue, but because of its slow kinetics for recovery from sodium channel block, little additional change in Vmax occurs within physiologically relevant heart rates and prematurity intervals.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D005449:Fluorenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D005449:Fluorenes; D007473:Ion Channels; C042398:indecainide; D012964:Sodium