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The authors evaluated the effects of verapamil (Ve) and magnesium sulfate (Mg) on the electrophysiologic changes induced in dogs during acute myocardial ischemia and following reperfusion. The effects of their intravenous (i.v.) administration and administration by coronary sinus retroperfusion (CSR) were also compared. Sixty-five dogs were divided into five groups: Ve-i.v.: 9 dogs, 0.1 mg/kg; Ve-CS: 9 dogs, 0.05 mg/kg; Mg-i.v.: 12 dogs, 20 mg/kg; Mg-CS: 11 dogs, 10 mg/kg, control: 24 dogs. The left anterior descending coronary artery was ligated for ten minutes, then quickly reopened. The changes in ventricular effective refractory period (ERP) and intramyocardial conduction time (ICT) were determined during ischemia and following reperfusion. The authors observed a shortening of the ERP and a prolongation of the ICT in the control group versus an attenuation of those effects in all other groups. The ERP was shortened to a lesser extent in the Mg-i.v. group than in the Ve-i.v. group. Drug administration by CSR inhibited the changes in ERP and ICT to a greater extent than i.v. administration, even though the dose given by CSR was one-half the i.v. dose. Ventricular fibrillation (Vf) occurred in 12 of 24 dogs (50%) in the control group during ischemia, and in 5 of 12 dogs (41.7%) following reperfusion. Vf occurred during ischemia and following reperfusion, respectively, in 22.2% and 0% in the Ve-i.v. and Ve-CS groups, in 25% and 22.2% in the Mg-i.v. group, and in 9.1% and 10% in the Mg-CS group. Thus, verapamil and magnesium sulfate inhibited the electrophysiologic changes and prevented ventricular arrhythmias during myocardial ischemia and following reperfusion. Administering the antiarrhythmic agent by coronary sinus retroperfusion may be useful for treating patients with acute myocardial infarction with intractable arrhythmias, according to these experimental results.

The efficacy of isoproterenol, MgSO4 and verapamil for torsade de pointes was evaluated in 60 dogs. Torsade de pointes was induced in 28 out of 60 dogs (46.7%) by ventricular stimulation after administration of quinidine sulfate (30 mg/kg). The electrophysiologic effect of isoproterenol (0.5 micrograms/min drip infusion) was studied in 9 dogs with torsade de pointes, in 9 dogs with MgSO4 (30 mg/kg), and in 10 dogs with verapamil (0.1 mg/kg bolus injection followed by 0.01 mg/kg/min drip infusion). If the first dose of these drugs was ineffective, ventricular stimulation was performed after the additional administration of the same dose. Isoproterenol significantly decreased QTc, ERP and dispersion of ERP but increased ERP/QT. MgSO4 significantly increased ERP and ERP/QT, however dispersion of ERP did not change. Verapamil induced no electrophysiologic changes in ventricular refractions . Isoproterenol prevented the occurrence of torsade de pointes in all dogs (100%), MgSO4 in 7 of 9 dogs (77.8%, 30 mg/kg in three and 60 mg/kg in four) and verapamil in 4 of 10 dogs (40%, 0.1 mg/kg in two and 0.2 mg/kg in two). These findings suggest that isoproterenol and MgSO4 increased ERP/QT, showing one of their antiarrhythmic effects. It also shows that isoproterenol and MgSO4 may be useful in the treatment of torsade de pointes.

The effect of magnesium sulfate on ventricular refractoriness and its efficacy for torsade de pointes (TdP) were studied in nineteen dogs. After the administration of quinidine sulfate (30 mg/kg), TdP was induced by ventricular pacing in ten of 19 dogs (52.6%), polymorphic ventricular tachycardia in seven (36.8%), ventricular fibrillation in two (10.5%). Quinidine sulfate caused significant increases in QTc interval, ventricular effective refractory period (ERP) and dispersion of ERP(dERP), and decrease in ERP/QT. Magnesium sulfate significantly increased ERP (p less than 0.01), but it did not change QT interval, resulting in significant increasing of ERP/QT (0.41 +/- 0.05 to 0.61 +/- 0.05, p less than 0.01). It decreased dERP but not significantly. Magnesium sulfate prevented the induction of TdP in eight of 10 dogs (80.0%) (30 mg/kg in four and 60 mg/kg in four). In conclusion, magnesium sulfate has value as first aid therapy for drug-induced TdP. If patients have ischemic heart disease or hypertension, we recommend infusion of magnesium for the initial therapy of TdP.

Electrophysiological studies were performed to evaluate the effects of MgSO4 on human conduction system. Nine patients who received 20 mg/kg of MgSO4 did not show any significant changes in the electrophysiological parameters except for prolongations in the PR and AH intervals. After the infusion of 40 mg/kg of MgSO4 in eleven patients, sinus cycle length and corrected sinus node recovery time were increased but statistically insignificantly. Sinoatrial conduction time, the PR interval and AH interval were increased. The effective refractory period (ERP) of right atrium, ERP of atrioventricular node (AV node), ERP of right ventricule and ERP/QTc were increased significantly. These findings suggests that the antiarrhythmic effects of magnesium were due to (1) suppression of the functions of the sinus and AV nodes, and (2) shortening of the duration of the ventricular vulnerable period during the cardiac cycle and prevention of ventricular arrhythmias related reentry mechanism.