Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs.

The choice of an adequate model for the study of antiarrhythmic drugs, relevant to the clinical problem of life-threatening arrhythmia, is a difficult and important task for contemporary cardiovascular pharmacology. Guided by pathophysiological considerations, we have designed an arrhythmia model in which ventricular tachyarrhythmias can be reproducibly elicited by combining the two clinically relevant stimuli of acute myocardial ischemia and augmented sympathetic activity. In anesthetized cats, following ablation of the right stellate ganglion, the left anterior descending coronary artery is occluded for 2 min. After 1 min of occlusion the left stellate ganglion is electrically stimulated for 30 s. In most experiments ventricular tachyarrhythmias, usually ventricular tachycardia or fibrillation, can be regularly elicited for six to eight trials. The consistency of the arrhythmic response allows an internally controlled study, since a drug may be administered after three trials under control conditions. This avoids the limitations due to individual variability of comparisons between groups. This model seems to be particularly well suited for preliminary evaluation, before final study in conscious animals, of drugs thought to have a protective effect against malignant arrhythmias associated with acute myocardial ischemia.