This study was initiated to determine if ventricular
arrhythmia induced by
digoxin was associated with a nonuniform neural discharge in the cardiac sympathetic postganglionic fibers. In addition, splanchnic neural discharge was monitored to explore the role of adrenal medullary
catecholamines in
digoxin-induced
arrhythmia. Experiments were performed to ascertain whether the antiarrhythmic effects of
quinidine in
digoxin-induced arrhythmias were related to an action on cardiac sympathetic neural discharge induced by
digoxin. All cats were anesthetized with
alpha-chloralose and given
atropine; some were pretreated with
quinidine (10 or 20 mg/kg i.v. 15 min before
digoxin).
Digoxin was given every 15 min until death; the first three doses were 50 micrograms/kg i.v., and all subsequent doses were 25 micrograms/kg. The mean +/- SE time to
arrhythmia was 32 +/- 4 min (n = 16) and was significantly increased only after 20 mg/kg
quinidine (64 +/- 7 min; p less than 0.001). Mean +/- SE time to death was also increased from 74 +/- 4 to 98 +/- 7 min (p less than 0.001). Postganglionic cardiac sympathetic neural discharge before
digoxin-induced
arrhythmia was depressed. Of the 28 nerves monitored in 16 animals receiving
digoxin, in the minute before development of
arrhythmia, 22 nerves were depressed, 3 were increased, and 3 showed no change when compared with the predigoxin control. Following this depression of neural discharge,
arrhythmia developed, and the neural discharge began to rise, eventually increasing above control levels. During this time the variability of the neural discharge increased greatly, as evidenced by large SE values, so that the mean values were not significantly different from control levels. Splanchnic neural discharge (n = 9) progressively decreased, reaching 66% of control values after the third injection of
digoxin; the discharge then began to increase gradually toward control levels in the next 10 min and
arrhythmia developed. The data indicate that the arrhythmias caused by
digoxin are not associated with the development of nonuniform discharge patterns in the cardiac sympathetic nerves. Furthermore, action on the splanchnic nerve discharge is not involved in the arrhythmogenic effects of
digoxin. Pretreatment with
quinidine, 20 mg/kg, decreased both splanchnic and post-ganglionic cardiac sympathetic neural discharge, arterial blood pressure, and heart rate. Although
quinidine, 20 mg/kg, increased the time to
arrhythmia induced by
digoxin, the depression of postganglionic cardiac or splanchnic neural discharge did not seem to be a major component of the antiarrhythmic effect of
quinidine.