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Circ Res. 1985 Oct;57(4):578-90.

Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity.

Abstract

The mechanisms by which lidocaine brings about negative inotropic effects and antiarrhythmic actions in the heart have been examined. Using sheep cardiac Purkinje fibers, we studied the effects of "therapeutic" concentrations of lidocaine (20 microM lidocaine = 5.4 micrograms/ml) on electrical activity, intracellular sodium activity, and tension. For the preparation with a normal, physiological level of intracellular sodium activity (5-9 mM), the application of lidocaine leads to the following actions: action potential duration is decreased, intracellular sodium activity falls, and twitch tension is reduced. If intracellular sodium activity is first elevated (e.g., by sodium pump inhibition) so that arrhythmogenic transient depolarizations (and the underlying transient inward current are seen) then lidocaine has the following actions: The action potential duration is reduced. There is a reduction of the magnitude of the arrhythmogenic transient depolarization (or the underlying membrane current transient inward current). The magnitude of the aftercontraction that accompanies the transient depolarization (or transient inward current) is reduced. If, after sodium pump inhibition, intracellular sodium activity is still rising-then, the application of lidocaine leads to a reduction of the rate of rise of intracellular sodium. From these results, parallel voltage-clamp experiments, and recent work by others, we conclude that lidocaine leads to the reduction of the arrhythmogenic transient depolarization and a reduction of twitch tension by decreasing the inward sodium current. These actions are mediated by a reduction in action potential duration and a reduction of intracellular sodium activity and of intracellular calcium activity (by the sodium-calcium exchange mechanism).

PMID:
2412723
[PubMed - indexed for MEDLINE]
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