title: Combined effect of disopyramide and erythromycin on ventricular repolarization in dogs with complete atrioventricular block.
abstract: The combined effects of disopyramide (DP) and erythromycin (EM) on ventricular repolarization and the inciden-ces of ventricular premature contractions (VPCs) and torsades de pointes (TdP) were investigated in 12 anesthetized dogs with complete atrioventricular block. Monophasic action potentials (MAPs) were measured from the left and right ventricular (LV and RV) endocardium. The right or left ventricle was paced at a cycle length of 750-1000 msec. Dogs were divided into 2 groups and given either intravenous DP at 3 mg/kg and then intravenous EM at 50 mg/kg (group 1, n = 8), or intravenous EM at 50 mg/kg and then intravenous DP at 3 mg/kg (group 2, n = 4). MAP duration at 90% repolarization (MAPD(90)) was measured before drug administration (baseline) and again after administration of each drug. RV MAPD(90) and LV MAPD(90) increased significantly (P < 0.02) after administration of each drug in group 1 (RV MAPD(90): from 247.0 ± 36.3 [baseline] to 283.5 ± 38.3 to 321.8 ± 56.7; LV MAPD(90): from 262.6 ± 49.1 (baseline) to 296.1 ± 58.8 to 351.0 ± 80.6). Early afterdepolarizations developed in 2 group 1 dogs after administration of DP and in 4 additional dogs after administration of EM. Frequent VPCs occurred in 1 dog after administration of DP and in 2 additional dogs after administration of EM, and TdP and ventricular tachycardias developed in 2 of the 3 dogs after administration of EM. Similar trends occurred in group 2. These results indicate a potentially fatal interaction between DP and EM administered in clinically relevant doses.
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Watanabe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Okumura
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagashima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kofune
authors.forename: Kimie
authors.initials: K
authors.lastname: Ohkubo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mano
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sonoda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasamaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D054537:Atrioventricular Block / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004206:Disopyramide / Q000008:administration & dosage*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects*; D004917:Erythromycin / Q000008:administration & dosage*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D011379:Prognosis; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D011500:Protein Synthesis Inhibitors; D004917:Erythromycin; D004206:Disopyramide