Effect of 6-Hydroxydopamine on Cardiotoxicity of Ouabain in Guinea Pigs

Saito, Hideya; Otani, Toru; Shudo, Isami; Tanabe, T.

doi:10.1254/jjp.24.923

Cited by 11 publications

(3 citation statements)

References 3 publications

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“…Two series of experiments were performed. In the first we adopted the procedure of Saito et al (1974). Naloxone (Dupont) dissolved in 0.1 ml of 0.9% NaCl solution in doses of 2.2 and 11 mg/kg, or 0.1 ml of 0.9% NaCl solution alone as control were administered intravenously 5 min before administration of ouabain.…”

Section: Methodsmentioning

confidence: 99%

Prevention and Reversal of Ouabain‐induced Cardiotoxicity by Naloxone in the Guinea‐pig

Lee

Unang

Wong

1986

Clin Exp Pharma Physio

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The effects of pre- and post-treatment with naloxone on the cardiotoxicity of ouabain in the guinea-pig were studied. After pretreatment with naloxone, the dose of ouabain required to induce ventricular arrhythmias and cardiac arrest were significantly increased, in a dose-dependent manner, compared with the control, indicating a protective effect of naloxone against digitalis intoxication. Administration of naloxone at the onset of cardiac arrhythmias induced by a lethal dose of ouabain restored the cardiac rhythm and consequently saved life in seven out of eight animals, indicating an antiarrhythmic effect of naloxone in digitalis-intoxicated guinea-pigs. The protective and antiarrhythmic effects of naloxone against digitalis intoxication have clinical implications.

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Section: Methodsmentioning

confidence: 99%

Prevention and Reversal of Ouabain‐induced Cardiotoxicity by Naloxone in the Guinea‐pig

Lee

Unang

Wong

1986

Clin Exp Pharma Physio

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“…There is, however, the possibility that in the 6-OHDA experiments, adrenergic block ade by CGS could contribute to the antiar rhythmic actions of the drug since 6-OHDA does not produce a complete depletion of catecholamines from the adrenal medulla [ 15], Evidence for this possibility is provided by previous experiments by Lathers et al [6,7] in which reserpine, an agent known to deplete adrenal catecholamines [16] pro tected against ouabain-induced arrhythmia, but cats treated with 6-OHDA were not pro tected. Some adrenergic neurons remain in tact after treatment with 6-OHDA [17], Thus, catecholamines from these neurons and from the adrenal medulla may explain why the heart rate was not significantly de creased by the pretreatment with 6-OHDA or by the addition of CGS (20 mg/kg, i.v.).…”

Section: Discussionmentioning

confidence: 99%

Protection of CGS 10078B against Ouabain-Induced Arrhythmia in the Cat

Lathers¹,

Tümer²,

Frame³

et al. 1987

Pharmacology

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CGS 10078B (CGS; l-[2,3-dihydro-l,4-(2S)-benzodioxm-2-yl]-5-[2,3-dihydro-1,4-(2i?)-benzodioxin-2-yl]-3-(1R,55)-aza-1,5-pentanediol methane sulfonate) is an agent with α- and β-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with α-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 μg/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p < 0.05) from control (165 ± 6 vs. 96 ± 7, and 136 ± 5 vs. 90 ± 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p < 0.05) from 225 ± 17 to 166 ± 14 and from 193 ± 8 to 152 ± 6beats/min. 11 min after T, BP and HR had decreased (p < 0.05) from 133 ± 6 to 103 ± 7 mm Hg and from 134 ± 4 to 104 ± 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p < 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.

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“…Surgical or pharmacological procedures that decrease sympathetic nerve function also decrease digitalis toxicity. Even though many groups of drugs which decrease sympathetic tone, like fl-adrenoceptor antagonists (Kelliher & Roberts, 1974;Hernandez & Serrano, 1982;, ganglion blocking agents (Gillis et al, 1975), drugs interfering with catecholamine storage and release Saito et al, 1974) were studied and found effective against cardiac arrhythmias induced by various cardiac glycosides, there has been no serious attempt to study the effect of a2-adrenoceptor agonists against digitalis-induced cardiotoxic effects. Numerous studies have proposed that clonidine reduces blood pressure by a reduction in sympathetic tone through activation of central a2-adrenoceptors (Schmitt, 1977;Isaac, 1980;Van Zwieten & Timmermans, 1983).…”

Section: Introductionmentioning

confidence: 99%

Protective action of clonidine against the arrhythmogenic and lethal effects of ouabain in guinea‐pigs

Thomas

Stephen

1991

British J Pharmacology

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1 Clonidine (1.25, 2.5 and 5.0 pugkg -) was studied for its effect on the cardiac arrhythmias and lethality induced by slow intravenous infusion of ouabain in guinea-pigs. 2 Clonidine produced significant delays in the onset of the arrhythmic stages and lethality. However, clonidine did not offer any such protection in reserpinised guinea-pigs, whereas its effects were unaltered in atropinized guinea-pigs.3 Idazoxan (l00.ugkg-1, i.v.) abolished the antiarrhythmic effect of clonidine whereas corynanthine(1 mg kg-1, i.v.) had no such effect. 4 Clonidine inhibited the rate of the ouabain-induced rise in blood pressure and the peak pressor response.5 In isolated paced left atria of the guinea-pig, clonidine (3.75 x 1O-4M) did not offer any protection against rapid and/or irregular extrasystolic contractions induced by ouabain. 6 It is concluded that the antiarrhythmic effect of clonidine is due to its effects on the indirect neural components of digitalis toxicity mediated by the stimulation of a2-adrenoceptors, without any direct antiarrhythmic effect on the myocardium.

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Effect of 6-Hydroxydopamine on Cardiotoxicity of Ouabain in Guinea Pigs

Cited by 11 publications

References 3 publications

Prevention and Reversal of Ouabain‐induced Cardiotoxicity by Naloxone in the Guinea‐pig

Prevention and Reversal of Ouabain‐induced Cardiotoxicity by Naloxone in the Guinea‐pig

Protection of CGS 10078B against Ouabain-Induced Arrhythmia in the Cat

Protective action of clonidine against the arrhythmogenic and lethal effects of ouabain in guinea‐pigs

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