Effects of ambasilide in isolated perfused guinea pig heart: use dependence

There has been increased interest in class III antiarrhythmic drugs for con-version of atrial fibrillation to sinus rhythm. Ambasilide, a class III antiarrhythmic, has been shown to block multiple cardiac channels in a variety of animals including humans. Although the electrophysiological effects of...

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Bibliographic Details
Published in:Cardiovascular toxicology 2005-01, Vol.5 (1), p.53-62
Main Authors: Kijtawornrat, Anusak, Hamlin, Robert L, Hamlin, David M
Format: Article
Language:English
Subjects:
Aminobenzoates - adverse effects
Aminobenzoates - pharmacology
Animals
Bridged Bicyclo Compounds, Heterocyclic - adverse effects
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cardiac arrhythmia
Dose-Response Relationship, Drug
Guinea Pigs
Heart - drug effects
Heart - physiology
In Vitro Techniques
Long QT Syndrome - chemically induced
Long QT Syndrome - physiopathology
Male
Perfusion
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Summary:There has been increased interest in class III antiarrhythmic drugs for con-version of atrial fibrillation to sinus rhythm. Ambasilide, a class III antiarrhythmic, has been shown to block multiple cardiac channels in a variety of animals including humans. Although the electrophysiological effects of ambasilide are characterized on the cellular level, its effects on an organ level have yet to be investigated. We investigated escalating doses of ambasilide in isolated, per-fused guinea pig hearts. Ambasilide prolonged the RR, PQ, QRS, QT, and QTc (F) in a concentration-dependent manner in either normal sinus rhythm or with reduced heart rate (atriectomy). dP/dtmin was increased (became less negative) in the presence of increasing concentrations of ambasilide, whereas the vehicle produced less negative lusitropy. Ambasilide demonstrated use dependence by prolonging QTc (F) less at slower heart rates. Ambasilide also inhibited isoproterenol-induced tachycardia, suggesting it exerts beta-adrenergic blocking properties. In conclusion, this study suggests that ambasilide has multichannel blocking properties including beta-adrenergic antagonism.
ISSN:1530-7905
1530-7905
1559-0259
DOI:10.1385/ct:5:1:053