Effects on rabbit cardiac potentials of aprindine and indecainide, a new antiarrhythmic agent, in normoxia and hypoxia

Abstract

1 Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations. 2 Both drugs depressed the maximum rate of depolarization (MRD) in a dose-related manner, indecainide being approximately ten times more potent than aprindine. 3 Aprindine caused a dose-related bradycardia, but indecainide had no significant effect on sinus node frequency. 4 Indecainide had a dose-related negatively inotropic effect in normal, half-normal and twice-normal extracellular calcium concentrations. 5 Indecainide shortened action potential duration (APD) in atrium and Purkinje cells but prolonged APD to 50% repolarization in ventricular muscle. 6 The actions of indecainide were extremely persistent. No significant recovery of MRD was observed after pauses in stimulation of up to 16 s. 7 Indecainide had no effect on effective refractory period (ERP) measured by interpolated premature stimuli. 8 Indecainide is therefore categorized as a Class Ic antiarrhythmic agent. 9 The effects of both aprindine and indecainide on MRD were increased in hypoxic atria. Conduction velocity in hypoxic atria exposed to indecainide was greater than in controls, however, suggesting the possibility of improved cell-to-cell coupling.

Persistence of the electrophysiologic effects of mexiletine in canine Purkinje fibers alters the response to subsequent hypoxia

“…Persistence of V, ; , , depression has also been noted after 90 min for aprindine (Dennis and Vaughan Williams 1985) and after 50 min for quinidine (Nattel and Bailey 1983). This persistence could reflect continued association of the drug with the receptor or a persistent alteration in the fast NaA channel.…”

“…To date, protection against hypoxic APD shortening has only been noted for drugs with persistence of &;,, depression: amexiletine (Burke and Berman 1985) and aprindine (Dennis and Vaughan Williams 1985). Cibenzoline, which also showed persistence of some electrophysiologic effects after 1 h of washout, also prevented hypoxic shortening of APD, but Purkinje action potentials were not studied after washout (Millar and Vaughan Williams 1982u).…”

“…Other investigators have noted similar effects in the course of their experiments. Dennis and Vaughan Williams ( 1985) report that aprindine, also considered a class 1B antiarrhythmic drug, 'khich alone caused a shortening of APB paradoxically reduced the shortening sf APD induced by hypoxia." Cibenzoline, a new antianhythmic drug, also considered to be a class 1 agent, prevented hypoxiainduced APD shortening, an effect Millar and Vaughan Williams (1982~) labelled '"rstection."…”

Profiles of Aprindine, Cibenzoline, Pilsicainide and Pirmenol in the Framework of the Sicilian Gambit

“…5,6 Qualitatively similar results were obtained by other investigators in cardiac tissues from guinea pigs or rabbits. [7][8][9][10][11] Aprindine-induced Vmax inhibition is enhanced in a frequency-and use-dependent manner. 5,7,9,10,[12][13][14][15][16] The onset and offset kinetics of use-dependent Vmax inhibition are intermediate.…”