Use of experimental myocardial infarct to demonstrate arrhythmogenic activity of drugs.
Ligature of the anterior interventricular coronary artery in the dog is a model that is used, classically, to study antiarrhythmic properties of drugs. It can also be used to demonstrate arrhythmogenicity. In this study, twenty hours after coronary ligature, cardiac arrhythmia was reduced by oral administration of quinidine and phenytoin. This effect lasted over several days after the coronary occlusion. By Day 2, more than 60% of the treated dogs had a predominantly sinus heart rhythm, compared with 20% of the controls. This antiarrhythmic treatment also seemed to reduce mortality. Dipyridamole was subsequently injected i.v. at 0.5 and 1 mg/kg on Days 2, 3, and 4 after coronary ligature. On Day 2, dipyridamole significantly increased the proportion of ectopic beats and significantly lowered the proportion of sinus beats. This drug can thus worsen arrhythmia induced by coronary occlusion. On Days 3 and 4, dipyridamole showed no arrhythmogenic effects, but there was a significant increase in sinus automaticity.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D010672:Phenytoin / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000139:chemically induced
D010672:Phenytoin; D004176:Dipyridamole; D011802:Quinidine