Arrhythmia models for drug research: classification of antiarrhythmic drugs

J Pharmacol Sci. 2007 Apr;103(4):333-46. doi: 10.1254/jphs.crj06013x. Epub 2007 Apr 4.

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. 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / classification
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / physiopathology
  • Biomedical Research / methods*
  • Biomedical Research / standards
  • Biomedical Research / trends
  • Humans
  • Models, Biological*

Substances

  • Anti-Arrhythmia Agents