Antifibrillatory action of bretylium: role of the sympathetic nervous system.
This study was performed to assess the role of cardiac sympathetic nerves in the in vivo antifibrillatory action of bretylium using the technique of electrically induced ventricular fibrillation. An initial study determined that 3 mg/kg of nortriptyline, an adrenergic amine uptake inhibitor, was sufficient to prevent the adrenergic neuron blockade produced by 5 mg/kg of bretylium in pentobarbital anesthetized dogs. Electrical ventricular fibrillation threshold (VFT) was then determined in two groups of pentobarbital anesthetized dogs using gated trains of increasing current applied to the epicardial surface of the right ventricle during atrial pacing. After determination of an initial VFT in both groups, one group of dogs (n = 8) received 3 mg/kg nortriptyline, the other group received saline (n = 9). The VFT was redetermined in both groups, after which all dogs received 5 mg/kg of bretylium, intravenously, and VFT was then measured at 15 and 90 min after bretylium. In saline-treated dogs, bretylium produced a significant increase in VFT from a control value of 6.9 +/- 1.6 mA (mean +/- SEM) to 31.0 +/- 0.5 mA at 15 min (p less than 0.05) and 45.1 +/- 4.8 mA at 90 min (p less than 0.05). In nortriptyline-treated dogs, however, nortriptyline itself produced an increase in VFT which was reversed by bretylium, and VFT after bretylium was not significantly elevated until 90 min to a value of 25.2 +/- 9.6 mA (control: 5.2 +/- 0.9 mA). These data demonstrate that pretreatment with nortriptyline attenuates and delays the onset of the acute antifibrillatory effect of bretylium and suggests a role for the cardiac adrenergic neuron as a potential target for part of the beneficial effects to be derived from antifibrillatory drugs.
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009661:Nortriptyline / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014439:Tyramine / Q000037:antagonists & inhibitors; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds; D009661:Nortriptyline; C045166:bretylium; D014439:Tyramine