title: Antiarrhythmic properties of a prior oral loading of amiodarone in in vivo canine coronary ligation/reperfusion-induced arrhythmia model: comparison with other class III antiarrhythmic drugs.
abstract: Amiodarone, which is generally classified as class III antiarrhythmic drug in the Vaughan Williams classification, is widely used for the treatments of refractory arrhythmias. However, we previously reported that intravenous infusion of amiodarone (6.67 mg/kg per hour) did not suppress arrhythmias induced by coronary ligation/reperfusion in dogs. In this study, we examined effects of a prior oral loading of amiodarone on arrhythmias induced by coronary ligation/reperfusion. Sixteen female beagle dogs (8.5 - 12.5 kg) were divided into two groups; one group was given amiodarone (40 mg/kg, orally, n = 8), and the other was given empty gelatin capsules (n = 8) 2 h before the operation. Dogs were anesthetized with pentobarbital and artificially ventilated. The left chest was opened, and the left anterior descending coronary artery was ligated for 30 min and then reperfused. The mean plasma concentration of amiodarone was over 1.3 mug/ml. Although the prior oral loading of amiodarone did not change the QT interval, amiodarone suppressed the number of ectopic beats during coronary ligation and the incidence of ventricular fibrillation during coronary ligation and reperfusion periods (P<0.05 vs control group). In conclusion, a prior oral loading of amiodarone suppressed arrhythmias induced by coronary ligation/reperfusion with a dose that did not prolong the QT interval. This antiarrhythmic property of amiodarone is different from those of the other class III drugs in that antiarrhythmic effects were accompanied by QT prolongation in our all previous studies.
authors.affiliation: Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi. ynaga@res.yamanashi-med.ac.jp
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Jianguang
authors.initials: J
authors.lastname: Chen
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000284:Administration, Oral; D000638:Amiodarone / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000601:surgery*; D004285:Dogs; D005260:Female; D008026:Ligation; D015425:Myocardial Reperfusion; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone