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.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|