Pharmacologic and behavioral effects on arrhythmias that immediately follow abrupt coronary occlusion: A canine model of sudden coronary death

Abstract

We have developed and studied a chronically instrumented canine model in which occlusion of a major coronary artery by an implanted balloon occluder promptly leads to arrhythmias that are reasonably reproducible on successive occlusions. Dogs were studied while conscious, and the electrocardiogram and electrograms from ischemic and nonischemic ventricular epicardium were recorded. Either the left anterior descending or circumflex coronary artery was occluded for up to 5.5 minutes. Experiments were performed in a carefully controlled environment at intervals sufficient for full recovery between occlusions. The arrhythmias that occurred were single or multiple premature ventricular depolarizations, runs of ventricular premature depolarizations or ventricular fibrillation. We measured the time from the onset of occlusion to the onset of arrhythmia (latency) and the severity of the arrhythmia (grade). Latency increased with successive occlusions in the same environment until no arrhythmia occurred during an occlusion of 5.5 minutes. In this state, addition of behavioral stress usually led to recurrence of arrhythmia. Stress decreased latency ( P < 0.02) and increased grade. We also studied the effects of tolamolol (a beta blocking agent), UM-272 (an analog of propranolol) and diazepam. Tolamolol increased latency ( P < 0.02) and tended to decrease grade. UM-272 had variable effects, but it clearly did not exert a protective action. The severity of arrhythmia was inversely related to latency, and latency decreased with increases in heart rate. The results obtained indicate that the model is useful for studies on arrhythmias that follow soon after the onset of ventricular ischemia, and they emphasize the relation between stress, enhanced sympathetic activity and ventricular arrhythmias.