The mechanism by which magnesium therapy suppresses some ventricular tachyarrhythmias characterized by a prolonged QT interval (e.g., torsades de pointes) is unknown. Since early afterdepolarizations have been proposed as a cause of the long QT syndrome and the related ventricular tachyarrhythmias, we hypothesized that magnesium therapy would suppress both the early afterdepolarization and the ventricular arrhythmias. The present study was performed to test the hypothesis. Using monophasic action potentials (MAP) recorded with a contact electrode from the right ventricular endocardium to demonstrate early afterdepolarizations, cesium chloride (168 mg/kg iv) was administered, before, during, and 1 to 2 hr after discontinuation of a magnesium infusion (1 to 2 mg/kg min for 20 to 30 min). Before magnesium infusion, cesium induced early afterdepolarizations that were 49.7 ± 1.6% (mean ± SE) of the amplitude of the corresponding monophasic action potential. The amplitude of the early afterdepolarization decreased to 31.2 ± 3.8% of the MAP amplitude during magnesium infusion (p < .003) and increased to 48.0 ± 4.0% 1 to 2 hr after termination of the magnesium infusion (p < .003). Cesium induced sustained monomorphic ventricular tachycardia, torsades de pointes, or ventricular fibrillation in 12 of 13 dogs before magnesium infusion, and in eight of 11 dogs 1 to 2 hr after stopping infusion, but in only three of 13 dogs during magnesium infusion. Cesium prolonged the corrected QT interval from 338 ± 16 msec (control) to 387 ± 14 msec before (p < .003), 356 ± 12 msec during (p < .003), and 406 ± 16 msec after stopping the magnesium infusion (p < .003). Magnesium also suppressed early afterdepolarizations induced with cesium in isolated canine Purkinje fibers. These data support the conclusion that magnesium's mechanism of action is to suppress early afterdepolarizations, prolonged QT interval, and ventricular tachyarrhythmias induced by cesium. Successful responses in patients may occur by a similar mechanism of early afterdepolarization suppression.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)