Effects of microinjection of ouabain into the hypothalamus in cats

1. In cats anaesthetized with chloralose, repeated injections of 20 mug ouabain were made either into the cerebral ventricles, or into the ventromedial nucleus of the hypothalamus (VMH), or intravenously whilst the electrocardiogram, arterial blood pressure and respiration were recorded.2. The injections produced cardiac arrhythmias preceded by sinus bradycardia, variable changes in arterial blood pressure and respiratory depression. Death occurred either from ventricular fibrillation or from cardiac arrest.3. The arrhythmias which occurred after the injections into the cerebral ventricles were not peripheral effects produced after absorption of the ouabain into the blood stream, because with intravenous injections larger amounts were required to produce the arrhythmias and to cause death than with intraventricular injections. The arrhythmias which resulted in death were due to an action on the VMH. With microinjections of ouabain into this region of the brain death occurred earlier and after smaller doses than after intraventricular injections.4. While sinus bradycardia was abolished by bilateral vagotomy other cardiac arrhythmias were prevented by acute cardiac sympathectomy and cervical cord transection. Thus both the sympathetic and parasympathetic nervous systems appear to be involved in the production of these arrhythmias.5. Since some of the cardiac arrhythmias obtained with ouabain in anaesthetized cats resemble the cardiotoxic effects seen in clinical practice during treatment with digitalis glycosides it is concluded that these effects, too, are, at least in part, central in origin, caused by an action on the VMH and mediated mainly via the sympathetic nervous system.