General systemic effects and electrocardiographic changes following injections of digitalis glycosides into the lateral ventricle of the brain

Melville, K. I.; Shister, H. E.

doi:10.1016/0002-8703(57)90177-1

Cited by 24 publications

(3 citation statements)

References 7 publications

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“…They suggested that the arrhythmias which were abolished by pentobarbital and by ganglion blocking drugs were of central origin, because they were not produced when the same doses of strophanthin were injected intravenously. Cardiac arrhythmias were also observed by Melville & Shister (1957) with injections of digitalis glycosides into the lateral ventricles of unanaesthetized cats, and by Solti, Marton & Takacs (1959) in crosscirculation experiments on dogs when strophanthin together with ephedrine was injected into the isolated head circulation; the arrhythmias occurred in the recipient dog. More recently, the development of arrhythmias following intravenous injections of ouabain in anaesthetized cats was shown to be associated with an increase of the spontaneous electrical activity in cardiac sympathetic, vagus and phrenic nerves (Gillis, 1969;Gillis, Levitt, Raines, Sohn & Standaert, 1969).…”

Section: Introductionmentioning

confidence: 85%

Effects of microinjection of ouabain into the hypothalamus in cats

Ray

Booker

Dutta

et al. 1972

British J Pharmacology

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Summary In cats anaesthetized with chloralose, repeated injections of 20 μg 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. 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. 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. 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. 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.

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Section: Introductionmentioning

confidence: 85%

Effects of microinjection of ouabain into the hypothalamus in cats

Ray

Booker

Dutta

et al. 1972

British J Pharmacology

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“…Intracerebroventricular (i.c.v.) injection of digitalis glycosides in minute doses produces marked neurotoxicity (Melville & Shister, 1957;Gaitonde et al, 1965). In this paper we have investigated the mechanism of neurotoxicity induced by cardiac glycosides in cats and elucidated the role of putative neurotransmitters in its genesis.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Neurotoxicity of Cardiotonic Glycosides

Gaitonde

Joglekar

1977

British J Pharmacology

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1In cats intracerebroventricular administration of 5, 10, 20 μg of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 μg of ouabain, produced marked neurotoxicity. This was dose‐related. 2Prior administration of reserpine (2 mg/kg i.m., 500 μg i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/kg i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/kg i.p., 2 mg i.c.v.) and haloperidol (200 μg i.c.v.) were ineffective. 3Prior administration of 2‐bromolysergic acid diethylamide (BOL‐148, 200 μg i.c.v.) or p‐chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4Perfusion of the lateral ventricles of cats with 10, 20 and 30 μg of peruvoside or ouabain produced a massive release of 5‐hydroxytryptamine (5‐HT). This was dose‐related. Prior administration PCPA suppressed the release of 5‐HT. 5The results of the findings indicate the involvement of 5‐HT in the genesis of neurotoxicity induced by peruvoside or ouabain.

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“…However, disruption of the neural pathways from the brain to tire spinal cord in cats did not influ ence ouabain toxicity except when there was a substantial reduction in heart rate, an impor tant factor in digitalis sensitivity (18). On the other hand, injection of cardiac glycosides either into the cerebral ventricles of dogs and cats (15,21,25) or into the ventromedial nucleus of tire hypothalamus and into certain medullary areas (1) produced cardiac arrhyth mias. However, all these effects are far from being specific since electrical or chemical stimulation of the brain by different drugs also produced a wide variety of electro cardiographic abnormalities and ventricular rhythms (12,26).…”

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confidence: 99%

Modification of the Cardiotoxic Effects of Ouabain by Acepromazine, Tetrodotoxin and Magnesium Sulphate

Peres-Gomes

Ribeiro

1979

Pharmacology

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Acepromazine (500 μg), tetrodotoxin (0.5 μg) and magnesium sulphate (7.5 mg twice) given intracerebroventricularly increased the doses of ouabain given by continuous intravenous infusion, required to induce arrhythmias and death. Acepromazine (150 μg kg^–1) was also effective when administered intravenously. Acepromazine (1.5 mg kg^–1) and tetrodotoxin (4-6μg kg^–1) given intravenously did not protect against, and even increased, the toxicity of ouabain. Both substances decreased blood pressure and increased heart rate. Tetrodotoxin, but neither acepromazine nor magnesium sulphate given intracerebroventricularly, induced a decrease in the heart rate before ouabain infusion. Acepromazine (500 μg) and tetrodotoxin (0.5 μg), but not magnesium sulphate, given intracerebroventricularly, decreased the blood pressure before ouabain infusion. The results are discussed in relation to the effects of those substances and ouabain on the circulation, and to the fact that the cardiac arrhythmias induced by high doses of ouabain and the protection obtained with tetrodotoxin and magnesium sulphate are, at least in part, mediated by the central nervous system.

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General systemic effects and electrocardiographic changes following injections of digitalis glycosides into the lateral ventricle of the brain

Cited by 24 publications

References 7 publications

Effects of microinjection of ouabain into the hypothalamus in cats

Effects of microinjection of ouabain into the hypothalamus in cats

Mechanism of Neurotoxicity of Cardiotonic Glycosides

Modification of the Cardiotoxic Effects of Ouabain by Acepromazine, Tetrodotoxin and Magnesium Sulphate

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