Robert E, Bruelle P, de La Coussaye J E, Juan J M, Brugada J, Peray P, Dauzat M, Eledjam J J
Department of Epidemiology and Biostatistics, Medical School of Montpellier-Nimes, France.
J Pharmacol Exp Ther. 1996 Jul;278(1):170-8.
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.
采用21个Langendorff灌注兔心和高分辨率标测技术来分析左心室心外膜激动情况，研究了丙咪嗪的电生理和促心律失常作用。在16个心脏中，通过心内膜冷冻技术（冷冻心脏）获取了一层薄薄的心外膜。5个心脏保持完整（非冷冻丙咪嗪治疗组）。在6个冷冻心脏中验证了标本稳定性。在10个冷冻心脏和5个非冷冻心脏中，分别给予0.01、0.1、1.0、2.0和5.0微克/毫升的丙咪嗪。在非冷冻丙咪嗪治疗的心脏中，丙咪嗪在5.0微克/毫升时诱发心动过缓（291.8±40.5对495.2±54.4毫秒，P = 0.02），在5.0微克/毫升时出现1例房室传导阻滞，在2.0和5.0微克/毫升时出现2例单形性室性心动过速（MVT）。在4/10的冷冻心脏中，在1.0微克/毫升丙咪嗪时诱发3例MVT，在2.0微克/毫升丙咪嗪时诱发1例MVT。所有MVT均基于围绕功能性传导阻滞线的折返。丙咪嗪（2.0微克/毫升）在起搏周期长度为1000毫秒时，使纵向和横向心室传导速度分别从71.7±6.1减慢至63.0±7.7厘米/秒（P = 0.008）和从32.9±2.6减慢至27.7±2.8厘米/秒（P = 0.009），并使心室有效不应期从141.9±9.3延长至279.1±112.6毫秒（P = 0.03）。丙咪嗪诱导剂量和使用依赖性的心室传导速度减慢，促进功能性传导阻滞和折返性MVT。
