BACKGROUND: In recent years, there has been an increasing use of antiarrhythmic drugs that act predominantly by prolonging myocardial repolarization. An inevitable electrophysiologic consequence of these drugs is the development of torsade de pointes as a proarrhythmic reaction. Both intravenous lidocaine and magnesium sulphate have been used in the acute control of such a proarrhythmia. Their electrophysiologic mechanisms in this setting are not well defined. METHODS AND RESULTS: Using the standard microelectrode techniques, the effects of magnesium (Mg) and lidocaine on action potential duration (APD), and on barium-induced spontaneous action potentials, were studied in canine Purkinje fiber preparations. The objective was to clarify the direct and indirect effects of magnesium on triggered activities due to early afterdepolarizations. Superfusion in media with 0.1 mM Mg and 2.5 mM K produced more pronounced increases in APD measured at -20mV repolarization time [APD(20)] than those in a solution with 5 mM K. This effect was further enhanced at lower stimulation frequencies. The striking prolongation of APD(20) by solutions with low potassium concentrations diminished as the Mg concentration was increased. In solutions with 2.5 mM K, Mg produced concentration-dependent decreases in APD(20). This effect was greater at lower stimulation frequencies. Lidocaine at 4.0 x 10(_5) M produced a marked shortening of the APD in the entire firing frequency of the abnormal automaticity in a concentration-dependent manner. With 10 mM Mg, such action potentials appeared only sporadically. Magnesium also decreased the amplitude and the maximum upstroke velocity of these action potentials. In contrast, lidocaine at 4.0 x 10(-5) M exhibited no significant effects on action potentials due to barium-induced abnormal automaticity, or on additional depolarizations developing from the repolarization phase of these action potentials. CONCLUSIONS: The data indicate that (i) hypomagnesemia may be arrhythmogenic when combined with hypokalemia and bradycardia leading to a prolongation of the plateau phase of the action potential, (ii) magnesium administration may suppress triggered activities mainly by a direct inhibition of the development of triggered potentials, and (iii) lidocaine may suppress triggered potentials only indirectly by preventing the development of early afterdepolarizations due to the shortening effect on the APD. These findings are consistent with the clinical observation of a high incidence of torsade de pointes in the setting of hypokalemia and hypomagnesemia introduced by a chronic diuretic therapy. They are also consistent with the marked effectiveness of intravenous Mg relative to the inconsistent clinical effects of lidocaine in controlling torsade de pointes.
BACKGROUND: In recent years, there has been an increasing use of antiarrhythmic drugs that act predominantly by prolonging myocardial repolarization. An inevitable electrophysiologic consequence of these drugs is the development of torsade de pointes as a proarrhythmic reaction. Both intravenous lidocaine and magnesium sulphate have been used in the acute control of such a proarrhythmia. Their electrophysiologic mechanisms in this setting are not well defined. METHODS AND RESULTS: Using the standard microelectrode techniques, the effects of magnesium (Mg) and lidocaine on action potential duration (APD), and on barium-induced spontaneous action potentials, were studied in canine Purkinje fiber preparations. The objective was to clarify the direct and indirect effects of magnesium on triggered activities due to early afterdepolarizations. Superfusion in media with 0.1 mM Mg and 2.5 mM K produced more pronounced increases in APD measured at -20mV repolarization time [APD(20)] than those in a solution with 5 mM K. This effect was further enhanced at lower stimulation frequencies. The striking prolongation of APD(20) by solutions with low potassium concentrations diminished as the Mg concentration was increased. In solutions with 2.5 mM K, Mg produced concentration-dependent decreases in APD(20). This effect was greater at lower stimulation frequencies. Lidocaine at 4.0 x 10(_5) M produced a marked shortening of the APD in the entire firing frequency of the abnormal automaticity in a concentration-dependent manner. With 10 mM Mg, such action potentials appeared only sporadically. Magnesium also decreased the amplitude and the maximum upstroke velocity of these action potentials. In contrast, lidocaine at 4.0 x 10(-5) M exhibited no significant effects on action potentials due to barium-induced abnormal automaticity, or on additional depolarizations developing from the repolarization phase of these action potentials. CONCLUSIONS: The data indicate that (i) hypomagnesemia may be arrhythmogenic when combined with hypokalemia and bradycardia leading to a prolongation of the plateau phase of the action potential, (ii) magnesium administration may suppress triggered activities mainly by a direct inhibition of the development of triggered potentials, and (iii) lidocaine may suppress triggered potentials only indirectly by preventing the development of early afterdepolarizations due to the shortening effect on the APD. These findings are consistent with the clinical observation of a high incidence of torsade de pointes in the setting of hypokalemia and hypomagnesemia introduced by a chronic diuretic therapy. They are also consistent with the marked effectiveness of intravenous Mg relative to the inconsistent clinical effects of lidocaine in controlling torsade de pointes.