Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Abstract

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. Ca2+-channel blockers and β-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. Keywords:: arrhythmia model, antiarrhythmic drug, proarrhythmic potential of drugs, ion channel, classification