title: Electrophysiologic and proarrhythmogenic effects of therapeutic and toxic doses of imipramine: a study with high resolution ventricular epicardial mapping in rabbit hearts.
abstract: 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.affiliation: Department of Epidemiology and Biostatistics, Medical School of Montpellier-Nimes, France.
authors.forename: E
authors.initials: E
authors.lastname: Robert
authors.forename: P
authors.initials: P
authors.lastname: Bruelle
authors.forename: J E
authors.initials: JE
authors.lastname: de La Coussaye
authors.forename: J M
authors.initials: JM
authors.lastname: Juan
authors.forename: J
authors.initials: J
authors.lastname: Brugada
authors.forename: P
authors.initials: P
authors.lastname: Peray
authors.forename: M
authors.initials: M
authors.lastname: Dauzat
authors.forename: J J
authors.initials: JJ
authors.lastname: Eledjam
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology*; D011817:Rabbits; D016276:Ventricular Function / Q000187:drug effects* / Q000502:physiology
chemical_list: D007099:Imipramine