Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.
We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.
D000200:Action Potentials; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology*
D011189:Potassium Chloride; D008012:Lidocaine; D011802:Quinidine