Effect of ouabain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic...

Cardiac arrhythmias induced by central nervous system stimulation in the cat were used to evaluate the possible central nervous system effects of ouabain and diphenylhydantoin. Electrical stimulation of the posterior portion of the hypothalamus resulted in alterations of cardiac rhythm, and recordings from cardiac-bound sympathetic nerves revealed continuous activity during the time of arrhythmia. Intravenous administration of small doses of ouabain (i.e., 10-30 mug/kg) prevented both the arrhythmias and the associated hyperactivity on the sympathetic nerves. The antiarrhythmic effect was not present in animals with denervated baroreceptors indicating that the ouabain effects were due to sensitization of baroreceptor reflexes. Intravenous administration of large but subarrhythmic doses of ouabain (i.e., 60-80 mug/kg) converted a subarrhythmogenic hypothalamic electrical stimulus to a threshold stimulus for arrhythmias. The increased response of the heart to brain stimulation in the presence of these doses of ouabain was associated with an increased discharge of cardiac sympathetic nerves, indicating that ouabain was exerting its arrhythmogenic enhancing effect on the central nervous system rather than on the heart. Pretreatment with diphenylhydantoin prevented the arrhythmias produced by the combination of ouabain and hypothalamic stimulation. Prevention of the arrhythmia was associated with prevention of the associated sympathetic hyperactivity responsible for the arrhythmia, thus indicating a central nervous system site of action of diphenylhydantoin. These data suggest that central nervous effects of ouabain and diphenylhydantoin are important in the ability of these drugs to alter cardiac rhythm.