Cyclic flow variations in a conscious dog model of coronary artery stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans

Abstract

Objectives. The purpose of this study was to test the hypothesis that episodes of cyclic flow variations (CFVs) in conscious dogs with coronary stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans.Background. Although the canine model with CFVs has proved to be a useful model of coronary thrombosis, whether CFVs progress to these syndromes has not been clearly described.Methods. Cyclic flow variations were produced by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery and 24-h Holter electrocardiogram (ECG) were recorded during the 1st 5 postoperative days.Results. Of 41 dogs that underwent the initial operative procedure successfully, 29 developed an episode of CFVs. In five dogs in which CFVs persisted throughout the monitoring period, the left anterior descending coronary artery flow decreased until day 3 and thereafter increased through day 5. Transient coronary occlusion during CFVs induced ST segment changes that returned to baseline after reflow. In 12 dogs, CFVs progressed to persistent coronary occlusion, and histologic examination revealed thrombus formation at the stenotic site and evidence of myocardial infarction. Four of these 12 dogs died suddenly of ventricular arrhythmias during persistent coronary occlusion; another 5 dogs died of reperfusion arrhythmias during CFVs with no evidence of myocardial infarction.Conclusions. Conscious dogs with CFVs closely correlated with clinical acute ischemic heart disease syndromes, suggesting them to be a useful model for investigating the complex mechanisms of cellular interactions in the pathogenesis of these syndromes.