Effect of cardiac β-adrenergic blockade or denervation on cardiotoxicity of digoxin and an aminosugar cardenolide

Sylvia K. Puryear, Clinton B. Nash, Robert W. Caldwell

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

This study examined the role of cardiac β-adrenergic receptors and cardiac sympathetic and vagal nerves in the cardiotoxicity of 3-β-0-(4-amino-4.6-dideoxyβ-D-glucopyranosyl), digitoxigenin hydrochloride (ASI-254). Vagally intact dogs received a constant-rate intravenous infusion of either digoxin or ASI-254 in the presence and absence of practolol. Practolol pretreatment increased the dose of digoxin required to produce arrhythmias and markedly altered the pattern of toxicity. but did not alter the lethal dose. The terminal event was cardiac standstill rather than ventricular tibrillation as seen in digoxin control dogs. Practolol did not alter the toxic dose of ASI-254 and produced little change in the pattern of cardiotoxicity: both control and practolol-treated dogs died in cardiac standstill. Surgical sympathectomy did not alter the toxic dose of ASI-254. the character of toxicity. or the lethal dose compared to neurally intact dogs. However, vagal innervation may play a role in determining the type of cardiotoxicity produced by ASI-254. Vagotomy alone did not alter the toxic or the lethal dose of ASI-254: vagotomy did, however, alter the character of cardiotoxicity and terminal event. Our results indicate that ASI-254 infused intravenously does not interact with sites, central or peripheral, which activate the sympathetic nervous system. ASI-254 administered into the lateral ventricles produced signs of increased cardiac sympathetic nervous system activity. Tachycardia and arrhythmias produced by ICV ASI-254 appear to be neurally mediated since ganglionic blockade blunted these effects. These results suggest that ASI-254 is capable of interacting with central sympathetic nervous system structures, but in contrast to digoxin, access to these structures from intravenous administration is limited.

Original languageEnglish (US)
Pages (from-to)113-127
Number of pages15
JournalJournal of Cardiovascular Pharmacology
Volume3
Issue number1
DOIs
StatePublished - Jan 1 1981
Externally publishedYes

Keywords

  • ASI-254
  • Digitalis toxicity
  • Digoxin
  • β-Receptor blockade

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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