Effects of verapamil and magnesium sulfate on electrophysiologic changes during acute myocardial ischemia and following reperfusion in dogs: comparative effects of administration by intravenous and coronary sinus retroperfusion routes.
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.
Yamamoto
K
K
Second Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Bando
S
S
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D003331:Coronary Vessels; D004285:Dogs; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D008278:Magnesium Sulfate / Q000008:administration & dosage* / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010477:Perfusion / Q000379:methods; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000517:prevention & control*; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate; D014700:Verapamil