Arrhythmia models for drug research: classification of antiarrhythmic drugs.
The aim of this study was to classify antiarrhythmic drugs based on their effectiveness on 6 in vivo arrhythmia models, mainly using dogs. The models were produced by two-stage coronary ligation, digitalis, halothane-adrenaline, programmed electrical stimulation in old myocardial infarction dogs, coronary artery occlusion/reperfusion, or chronic atrioventricular block. Na(+)-channel-blocking drugs suppressed two-stage coronary ligation and digitalis arrhythmias. Ca(2+)-channel blockers and beta-blockers suppressed halothane-adrenaline arrhythmia. Positive inotropic drugs aggravated halothane-adrenaline arrhythmia, but did not aggravate digitalis arrhythmia. K(+)-channel blockers suppressed programmed electrical stimulation induced arrhythmia, but induced torsades de pointes type arrhythmia in chronic atrioventricular block dogs and aggravated halothane-adrenaline arrhythmia. Na(+)/H(+)-exchange blockers suppressed coronary artery occlusion/reperfusion arrhythmias. This classification may be useful for predicting the clinical effectiveness in the preclinical stage of drug development.
Hashimoto
Keitaro
K
University of Yamanashi, Shimokato, Chuo, Japan. keitaroh@yamanashi.ac.jp
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D035843:Biomedical Research / Q000379:methods* / Q000592:standards / Q000639:trends; D006801:Humans; D008954:Models, Biological
D000889:Anti-Arrhythmia Agents