Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs.
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 afterdepolarizations and the ventricular arrhythmias. The present study was performed to test that 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 less than .003) and increased to 48.0 +/- 4.0% 1 to 2 hr after termination of the magnesium infusion (p less than .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 less than .003), 356 +/- 12 msec during (p less than .003), and 406 +/- 16 msec after stopping the magnesium infusion (p less than .003).(ABSTRACT TRUNCATED AT 250 WORDS)
Bailie
D S
DS
Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
Inoue
H
H
Kaseda
S
S
Ben-David
J
J
Zipes
D P
DP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002586:Cesium / Q000633:toxicity*; D002712:Chlorides; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D004566:Electrodes; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D002712:Chlorides; D002586:Cesium; C028019:cesium chloride; D008274:Magnesium