ABSTRACT
The interactions of lidocaine (1-5 X 10(-5) M) and calcium ions (1.25-5.0 mM) on electrical characteristics of atrial potentials were determined with standard microelectrode techniques with major reference to the maximum rate of rise of the action potential (Vmax of AP), the time constant of recovery of the rapid sodium carrier (gamma) and repetitive firing due to early extra stimuli (arrhythmia). Lowering Ca caused depolarization and decreased Vmax and gamma; high Ca caused changes in the opposite direction. The relation of gamma to membrane potential was downward concave when membrane potential was changed by Ca but upward concave when equivalent changes in membrane potential were induced by changing the external potassium concentration. Lidocaine (1 X 10(-5) M) had no significant effect at 2.5 mM Ca but significantly decreased the overshoot and Vmax of AP, increased gamma and effective refractory period and was antiarrhythmic at 1.25 mM Ca. These changes were closely similar to the effects of lidocaine (5 X 10(-5) M) at 2.5 mM Ca. The effects of this high concentration were decreased when Ca was changed to 5.0 mM. The effect of lidocaine most clearly predictive of efficacy for the type of arrhythmia was that on Vmax, with changes in gamma in particular not being related to antiarrhythmic activity.
Subject(s)
Calcium/pharmacology , Heart/drug effects , Lidocaine/pharmacology , Action Potentials/drug effects , Animals , Drug Interactions , Female , Heart Atria/drug effects , In Vitro Techniques , Male , Membrane Potentials/drug effects , Osmolar Concentration , Rabbits , Refractory Period, Electrophysiological/drug effects , Sodium/physiologyABSTRACT
Standard microelectrode recordings were obtained from rabbit right and left atria. Lidocaine (1 X 10(-5) M) had no effect on these, but 5 X 10(-5) M lidocaine significantly slowed rate and Vmax. This concentration had no effect on the duration of the action potential, a result clearly different from the effect of this drug in Purkinje tissue. Lidocaine had much less effect on the 'steady-state' relation of membrane potential to Vmax of phase 0 of the action potential than on the 'membrane responsiveness curve' obtained by the extra stimulus technique. We have demonstrated time-related recovery from sodium inactivation in rabbit left atria and have shown that lidocaine slows recovery in this tissue as it does in Purkinje fibres.
