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.