Sympathetic activation triggers ventricular arrhythmias in rat heart with chronic infarction and failure.
OBJECTIVE
To seek direct evidence for a cause-effect relation between sympathetic 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 methods.


RESULTS
Infarcted rats showed cardiac functional impairment and increased heart and lung weight. The extent of these changes correlated well with infarct size (IS). In in situ perfused hearts, sympathetic nerve stimulation (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 groups. In hearts with large IS (> or = 40%, n = 19) ventricular arrhythmias were rare at baseline, but nerve stimulation evoked the onset of ventricular premature beats (95%), tachycardia (37%) and fibrillation (26%), IS and stimulation frequency were key determinants for the inducibility of arrhythmias. Lower K- concentration enhanced arrhythmia inducibility. beta-blockade inhibited the frequency of arrhythmias produced by nerve stimulation.


CONCLUSIONS
In infarcted rat hearts sympathetic activation is a potent trigger for the onset of ventricular tachyarrhythmias.
Du
X J
XJ
Alfred and Baker Medical Unit, Baker Medical Research Institute, Melbourne, Victoria, Australia. xiaojun.du@baker.edu.au
Cox
H S
HS
Dart
A M
AM
Esler
M D
MD
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012723:Sex; D018709:Statistics, Nonparametric; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C026777:ICI 118551; D001262:Atenolol; D011188:Potassium; D003891:Desipramine; D009638:Norepinephrine