Antagonism of deslanoside-induced cardiotoxicity by combined nicotinic and muscarinic blockade of autonomic ganglia

RA Gillis, H Jolson, H Thibodeaux and B Levitt

The effect of ganglionic blockade on cardiotoxicity induced by deslanoside (25 mug/kg i.v. at 15-minute intervals) was evaluated in Dial-urethane anesthetized cats. Electrocardiogram, blood pressure and pre- and postganglionic cardiac sympathetic nerve recordings were monitored. When deslanoside was given to control animals, 150 +/- 8.2 and 179 +/- 11.9 mug/kg produced ventricular tachycardia and ventricular fibrillation, respectively. Pretreatment of cats with either hexamethonium or atropine alone did not influence the doses of deslanoside required to produce ventricular tachycardia or ventricular fibrillation. However, pretreatment with the combination of hexamethonium and atropine significantly increased the dose of deslanoside needed to produce ventricular tachycardia (181 +/- 12.3 mug/kg) and ventricular fibrillation (219 +/- 12.3 mug/kg). Furthermore, administration of atropine to hexamethonium-pretreated cats intoxicated with deslanoside decreased deslanoside-induced postganglionic nerve activity. These results indicate that blockade of both nicotinic and muscarinic ganglionic transmission is essential for a protective influence against cardiotoxicity induced by deslanoside.

Volume 195, Issue 1, pp. 126-132, 10/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics