Sympathetic activation triggers ventricular arrhythmias in rat heart with chronic infarction and failure

Objective: To seek direct evidence for a cause-effect relation between symp athetic activation and arrhythmogenesis. Methods: Rats underwent open-chest surgery with either coronary artery occlusion or sham operation, and were studied 8 weeks later using in situ heart perfusion and nerve stimulation m ethods. Results: Infarcted rats showed cardiac functional impairment and in creased heart and lung weight. The extent of these changes con elated well with infarct size (IS). In in situ perfused hearts, sympathetic nerve stimu lation (2 and 4 Hz, 45 s duration) induced a frequency-dependent release of norepinephrine (NE). NE release was lower in MI than that in control group s. In hearts with large IS (greater than or equal to 40%, n=19) ventricular arrhythmias were rare at baseline, but nerve stimulation evoked the onset of ventricular premature bents (95%), tachycardia (37%) and fibrillation (2 6%). IS and stimulation frequency were key determinants for the inducibilit y of arrhythmias. Lower K+ concentration enhanced arrhythmia inducibility. beta-blockade inhibited the frequency of arrhythmias produced by nerve stim ulation. Conclusion: In infarcted rat hearts sympathetic activation is a po tent trigger for the onset of ventricular tachyarrhythmias. (C) 1999 Elsevi er Science B.V. All rights reserved.