Preclinical assessment of antiarrhythmic drugs

The morbidity statistics for the United States alone would suggest that there are 400,000 victims each year who succumb to sudden coronary death, which suggests that there is a need for the development of pharmacological interventions capable of preventing ventricular fibrillation (VF) in patients identified as being at high risk. A major deficiency in this area of experimental investigation is the lack of an animal model that would permit preclinical studies to identify potentially useful therapeutic agents. We have developed an experimental canine model of sudden coronary death in which VF occurs in the chronically injured heart that is subjected to a period of transient ischemia in a coronary region remote from the site of a previous myocardial infarction. The experimental model is subject to the induction of ventricular tachyarrhythmias in response to programmed electrical stimulation, thereby permitting the investigator to correlate the effectiveness of a pharmacological agent in preventing electrically induced arrhythmias with its potential to prevent the development of VF in response to ischemia at a site remote from a previous infarct. Thus, acute myocardial ischemia at a site distant from a previous myocardial infarction enhances the likelihood of primary VF in the conscious dog. This model of sudden coronary death may stimulate more closely the clinical state in humans and might serve as an appropriate model for the study of electrophysiological mechanisms associated with the development of VF and for the evaluation of potential antifibrillatory drugs.