Document Detail


Electrophysiologic and proarrhythmogenic effects of therapeutic and toxic doses of imipramine: a study with high resolution ventricular epicardial mapping in rabbit hearts.
MedLine Citation:
PMID:  8764348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Electrophysiologic and proarrhythmogenic effects of imipramine were studied by use of 21 Langendorff-perfused rabbit hearts and high-resolution mapping to analyze epicardial activation of the left ventricle. In 16 hearts, a thin layer of epicardium was obtained by an endocardial cryotechnique (frozen hearts). Five hearts were kept intact (nonfrozen imipramine-treated group). Preparation stability was verified in six frozen hearts. In 10 frozen and in 5 nonfrozen hearts, 0.01, 0.1, 1.0, 2.0 and 5.0 micrograms/ml imipramine were administered. In nonfrozen imipramine-treated hearts, imipramine induced bradycardia at 5.0 micrograms/ml (291.8 +/- 40.5 vs. 495.2 +/- 54.4 msec, P = .02), one A-V block at 5.0 micrograms/ml and two monomorphic ventricular tachycardias (MVT) at 2.0 and 5.0 micrograms/ml. In 4/10 frozen hearts, three MVT were induced at 1.0 microgram/ml imipramine and one MVT at 2.0 micrograms/ml imipramine. All MVT were based on reentry around a line of functional conduction blocks. Imipramine (2.0 micrograms/ml) slowed longitudinal and transversal ventricular conduction velocities at a pacing cycle length of 1000 msec from 71.7 +/- 6.1 to 63.0 +/- 7.7 cm/sec (P = .008) and from 32.9 +/- 2.6 to 27.7 +/- 2.8 cm/sec (P = .009), respectively, and prolonged ventricular effective refractory period from 141.9 +/- 9.3 to 279.1 +/- 112.6 msec (P = .03). Imipramine induced dose- and use-dependent slowing of ventricular conduction velocity facilitating functional conduction blocks and reentrant MVT.
Authors:
E Robert; P Bruelle; J E de La Coussaye; J M Juan; J Brugada; P Peray; M Dauzat; J J Eledjam
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  278     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-09-23     Completed Date:  1996-09-23     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  170-8     Citation Subset:  IM    
Affiliation:
Department of Epidemiology and Biostatistics, Medical School of Montpellier-Nimes, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / physiopathology*
Dose-Response Relationship, Drug
Electrophysiology
Heart / drug effects*
Imipramine / pharmacology*
Rabbits
Ventricular Function / drug effects*,  physiology
Chemical
Reg. No./Substance:
50-49-7/Imipramine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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