title: Prophylactic magnesium to decrease the arrhythmogenic potential of class III antiarrhythmic agents in a rabbit model.
abstract: We assessed the prophylactic effect of intravenous magnesium sulfate on the occurrence of torsades de pointes and early after-depolarizations, and on the QT interval (QTc) in an established rabbit model. Ten rabbits were given intravenous methoxamine to slow their heart rates. After 12 minutes five animals received a 60-mg/kg bolus and continuous infusion of magnesium 0.6 mg/kg/minute, and five received equivolume normal saline concurrently with the class III antiarrhythmic agent clofilium 5 mg/kg over 30 minutes. Electrocardiogram lead II and the monophasic action potential were recorded continuously throughout the experiment. The magnesium group experienced significantly less torsades de pointes and early after-depolarizations than the normal saline group (1/5 and 5/5 both parameters, respectively, p=0.048). There were no differences between groups in QT or QTc interval at baseline or at maximum QT or QTc prolongation. Magnesium decreases the occurrence of torsades de pointes without affecting the QT or QTc interval but does decrease the occurrence of early after-depolarizations. These findings must be validated in human studies.
authors.affiliation: University of Connecticut School of Pharmacy, Storrs, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: M S
authors.initials: MS
authors.lastname: Chow
authors.forename: J
authors.initials: J
authors.lastname: Kluger
mesh_terms: D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D004562:Electrocardiography / Q000187:drug effects*; D008274:Magnesium / Q000494:pharmacology*; D008729:Methoxamine / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000009:adverse effects*; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D016171:Torsades de Pointes / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; D013566:Sympathomimetics; C022799:clofilium; D008729:Methoxamine; D008274:Magnesium