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 RESEARCH PAPER
Year : 1983  |  Volume : 15  |  Issue : 2  |  Page : 123-141

Role of autonomic system in the negative chronotropic and arrhythmogenic effect of digoxin in dog



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H C Tripathi


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Digoxin was given intravenously in anaesthetized dogs in the dose of 25 'g/kg every 15 min till the animals died. ECG and carotid blood pressure were continuously monitored. Digoxin produced dose-dependent bradycardia. In physostigmine pretreated animals, the negative chronotropic activity of digoxin appeared to be slightly more than in the control animals. While atropine pretreatment did not appear to significantly affect the negative chronotropic activity of digoxin, but the negative chronotropic activity was found than to be less in vagotomized dogs than in the control dogs. These results indicate that part of the negative chronotropic activity of digoxin was mediated through cholinergic activation. Blockade of the adrenergic system, especially with the use of beta-adrenergic blocking agents, enhanced the negative chronotropic activity of digoxin. In this respect adrenal gland was not found to have any significant role. Propranolol pretreatment potentiated the negative chronotropic activity while adrenalectomy had no significant effect. It appeared that functional adrenergic activity partly offsets the negative chronotropic activity of digoxin. Continued administration of digoxin produced varieties of arrhythmias-bradyarrhythmias and tachyarrhythmias. Both types of arrhythmia were found to be present in the same dog in many of the cases.Terminal event was evoked in the form of ventri -cular fibrillation (VF) or cardiac arrest.The incidence of bradyarrhythmiar was found to be more in propranolol or physostigmias pretreated animals,On the other hand, the incidenece of bradyarrhythmine was low in vagotomized animals. Digoxin-induced tach arrhythmias were slightly but not significantly reduced by physostigmine or propranolol pretreatment, or in adrenalectomized dogs. It appeared that bradyarrhythmias were facilitated by cholinergic activity while tachyarrhythmias were not significanty affected by autonomic nervous system (ANS). In digitalized dogs, nearly half of the animals ended with VF and the other half in the cardiac arrest. None of the prapranolol pretreated dogs died of VF while all the vagotomized dogs died of VF. Physostigmine pretreatment reduced the incidence of VF. It seemed, therefore, that adrenergic activity potentiated digitalis-induced VF, while cholinergic activity had a protective role. Sub epicardial administration of digoxin in the concentration of 50 to 250 'g/ml at the rate of 10 'l/min for 5 min produced a unifocal ventricular extrasystole, the frequency of which was dependent on the concentration used. In none of the experiments, there was VF. These arrhythmias were always reversible. It was concluded that systemic administration of digoxin is more arrhythmogenic than the local administration, possibly because of activation of central and autonomic system along with the global effects digoxin on the heart whein given systemically. These focal arrhythmias could also be antagonized when administered along with propranolol.






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