title: Time course of the electrophysiological effects of quinidine on canine cardiac Purkinje fibers: concentration dependence and comparison with lidocaine and disopyramide.
abstract: We used standard microelectrode techniques to observe the time course of the appearance and disappearance of the cellular electrophysiologic effects of antiarrhythmic drugs during drug infusion and after washout. The slopes of phases 0 (Vmax), 2(V2) and 3(V3) of the action potential of canine Purkinje fibers were followed during 30 min of infusion of quinidine (0.2 - 1 x 10(-5) M), disopyramide (1 x 10(-5) M) or lidocaine (1 x 10(-5) M) and then during 60 min of washout with drug-free Tyrode's solution. All three drugs significantly reduced V3 and increased V2; quinidine and disopyramide also significantly reduced Vmax. The onset of the effects of quinidine and disopyramide on Vmax, V2 and V3 occurred at similar rates. Both the onset and disappearance of the effects of lidocaine were more rapid than those of quinidine and disopyramide. This may have been related to the greater lipid solubility of lidocaine with a heptane: water partition coefficient of 0.85 for lidocaine compared with 0.16 for disopyramide and 0.06 for quinidine. The effects of quinidine (1 x 10(-5) M) on V3 reversed much more slowly upon washout (T1/257 +/- 12 min, mean +/- S.E.) than the effects of quinidine on Vmax (T1/218 +/- 3 min, P less than .01) and V2 (T1/215 +/- 3 min, P less than .01). Concentration-response data showed that the time course of washout of the effects of quinidine was independent of drug concentration. These data suggest that rapidity of antiarrhythmic drug action is related to lipophilicity and that the effect of quinidine on V3 is due to action at a different cellular site from its effects on Vmax and V2.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D004206:Disopyramide; D011802:Quinidine