Effect of lidocaine hydrochloride on membrane conductance in mammalian cardiac purkinje fibers

Abstract

current-voltage relationships in long Purkinje fibers was corrected for cable complications or when experiments were done in short Purkinje fibers. To minimize complications due to membrane rectifier properties, GK was measured using intracellular application of small hyperpolarizing current pulses as Vm was decreased from -90 to -60 mv by increasing the [K]0 from 3 to 15 mM before and after lidocaine. Lidocaine increased the GK over this range of Vm.These results suggest that lidocaine increases membrane potassium conductance within the range of Vm where the pacemaker potential is seen, an action which can account for its ability to suppress automaticity, and, in part, for its ability to prevent reentrant arrhythmias. INTRODUCTIONThe efficacy of lidocaine hydrochloride in the treatment of cardiac ventricular arrhythmias after open heart surgery, myocardial infarction, and digitalis has been established and recently reviewed (1). Electrophysiologic investigations have shown that in cardiac Purkinje fibers, lidocaine: (a) shortens the action potential duration and decreases the effective refractory period, and (b) exerts an antiautomatic effect by decreasing the slope of slow diastolic depolarization without affecting the maximum diastolic transmembrane voltage (2-4). These observations led Bigger and Mandel to postulate that lidocaine may increase potassium conductance in mammalian cardiac Purkinje fibers (3). The present experiments were designed to test this hypothesis in sheep Purkinje fibers using microelectrode techniques. The effects of lidocaine in a concentration equivalent to clinical plasma antiarrhythmic levels on the transmembrane voltage and on current-voltage relationships suggest that lidocaine does increase potassium conductance in Purkinje fibers.

Mechanisms for impulse initiation in isolated human atrial fibers.

“…Agents that increase potassium conductance, lidocaine (Arnsdorf and Bigger, 1972) and ACh (Noble, 1975;Rayner and Weatherall, 1959), decreased the slope of phase 4 depolarization and automaticity. Lidocaine has been shown to increase i K i and to decrease the background inward current of sheep Purkinje fibers (Weld and Bigger, 1976).…”

Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia.

“…Chen et al demonstrated that this effect was due to a shift in the membrane potential per se and not a direct consequence of an increase extracellular K + . The results of Brennan et al suggest that an additional effect of lidocaine on the potassium outward current (Arnsdorf and Bigger, 1972), which could affect slow, calcium-dependent action potentials, is negligible if extracellular potassium is elevated and, consequently, potassium conductance is high prior to the administration of the drug. In the case of acute isolated human heart would not be sufficient to explain the marked depression of the upstroke velocity and the decrease in amplitude of the action potential in ischemia.…”

Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers. An effect on steady state sodium currents?

“…At clinically relevant concentrations (2-5 jig/ml), lidocaine is known to shorten the cardiac action potential (Davis and Temte, 1969;Bigger and Mandel, 1970), whereas quinidine generally produces a lengthening September 17, 1981. or no change (Vaughan Williams, 1958;Hoffman, 1958;Mirro et al, 1981). The basis for the quinidine effect on action potential duration has not been defined, whereas an increase of potassium conductance has been proposed to mediate the action of lidocaine (Arnsdorf and Bigger, 1972;Weld and Bigger, 1976). The question of whether effective antiarrhythmic action involves multiple drug target sites or interaction with one specific ionic channel is of importance.…”