title: Salutary antiarrhythmic effect of combining a K channel blocker and a beta-blocker in a canine model of 7-day-old myocardial infarction.
abstract: We sought to examine whether the antiarrhythmic effect of E4031 (E), or I(Kr) channel blocker, is affected by beta-adrenergic stimulation using isoproterenol (Iso) or by beta-adrenergic blockade (betaB) using, ONO1101, in a canine myocardial infarction model. Electrophysiologic studies were performed in 10 dogs with 7-day-old myocardial infarctions. Local QT intervals were measured at 47 sites on the infarcted myocardium using a mapping electrode. QT dispersion (QTd), as defined by the coefficient of variation of QT intervals, was obtained. Inducibility of ventricular arrhythmias was examined by programmed stimulation. These procedures were repeated during administration of E, E + Iso, and E + betaB. The effect of prolonging local QT intervals by E was counteracted by Iso, and was accentuated by betaB. The amount of prolongation was dependent on the baseline QT intervals, and QTd showed a tendency to decrease with E, to increase with E + Iso, and significantly decreased with E + betaB. Ventricular tachyarrhythmias were induced in a half of dogs with E + Iso, but were not induced with E + betaB. In the presence of adrenergic activation, I(Kr) blockers may exhibit a decreased antiarrhythmic effect. Beneficial synergism can be expected when an I(Kr) blocker is combined with a beta-blocker in the subacute phase of myocardial infarction.
authors.affiliation: Department of Medicine, Keio University, School of Medicine, Tokyo, Japan. seiji@med.keio.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Takatsuki
authors.forename: H
authors.initials: H
authors.lastname: Mitamura
authors.forename: H
authors.initials: H
authors.lastname: Kanki
authors.forename: K
authors.initials: K
authors.lastname: Sueyoshi
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011725:Pyridines / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D009025:Morpholines; D010880:Piperidines; D026902:Potassium Channel Blockers; D011725:Pyridines; C063968:E 4031; C077049:landiolol; D014508:Urea