TIME COURSE OF THE ELECTRO-PHYSIOLOGICAL EFFECTS OF QUINIDINE ON CANINE CARDIAC PURKINJE-FIBERS - CONCENTRATION-DEPENDENCE AND COMPARISON WITH LIDOCAINE AND DISOPYRAMIDE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (1) , 176-180
Abstract
Standard microelectrode techniques were used 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 O (.ovrhdot.Vmax), 2 (.ovrhdot.V2) and 3 (.ovrhdot.V3) of the action potential of canine Purkinje fibers were followed during 30 min of infusion of quinidine (0.2 - 1 .times. 10-5 M), disopyramide (1 .RTM. 10-5 M) or lidocaine (1 .times. 10-5 M) and then during 60 min of washout with drug-free Tyrode''s solution. All 3 drugs significantly reduced .ovrhdot.V3 and increased .ovrhdot.V2; quinidine and disopyramide also significantly reduced .ovrhdot.Vmax. The onset of the effects of quinidine and disopyramide on .ovrhdot.Vmax, .ovrhdot.V2 and .ovrhdot.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 .times. 10-5 M) on .ovrhdot.V3 reversed much more slowly upon washout (T1/2 [half life] 57 .+-. 12 min, mean) than the effects of quinidine on .ovrhdot.Vmax (T1/2 18 .+-. 3 min, P < 0.01) and .ovrhdot.V2 (T1/2 15 .+-. 3 min, P < 0.01). Concentration-response data showed that the time course of washout of the effects of quinidine was independent of drug concentration. Evidently rapidity of antiarrhythmic drug action is related to lipophilicity and the effect of quinidine on .ovrhdot.V3 is due to action at a different cellular site from its effects on .ovrhdot.Vmax and .ovrhdot.V2.