pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac purkinje fibers.
We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and Vmax, while increasing APD90 and conduction time. Lidocaine concentrations of 6 x 10(-6) to 1.5 x 10(-5) M had minimal effect on resting potential, action potential amplitude, and Vmax at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and Vmax (14-22%). Quinidine (6 x 10(-6) to 1.5 x 10(-5) M) reduced resting potential (3-5%), action potential amplitude (4-9%), and Vmax (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and Vmax (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in four of 14 experiments with 1.5 x 10(-5) M quinidine and in two of 10 with 1.5 x 10(-5) M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the Vmax-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D011690:Purkinje Fibers / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology*
D008012:Lidocaine; D011802:Quinidine