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 V̇max, while increasing APD90 and conduction time. Lidocaine concentrations of 6x10-6 to 1.5x10-5 M had minimal effect on resting potential, action potential amplitude, and V̇max at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and V̇max (14-22%). Quinidine (6x10-6 to 1.5x10-5 M) reduced resting potential (3-5%), action potential amplitude (4-9%), and V̇max (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 V̇max (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 4 of 14 experiments with 1.5x10-5 M quinidine and in 2 of 10 with 1.5x10-5 M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the V̇max-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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine