Befol (20 mg/kg) rises electric threshold of ventricular fibrillation in cats. This effect is most pronounced in ischemized myocardium. It is shown that not only tricyclic but also monocyclic antidepressants exhibit antifibrillatory activity.
Key Words: befol; ventricular fibrillation; ischemia, treatmentThe antidepressant befol, 4-chlorine-N-(3-morpholynopropyl)-benzamide hydrochloride, is a reversible inhibitor of monoamine oxidase (type A by serotonin substrate) synthesized at the Institute of Pharmacology (Russian Academy of Medical Sciences) [1,4]. Clinical trials showed that this drug possesses both antidepressant and antiarrhythmic activities [3,6].Therefore, it was interesting to assess the antifibrillatory activity (AFA) of befol, which is a monocyclic antidepressant, in animal experiments, bearing in mind the finding that some tricyclic antidepressants (metapramine, imipramine, and momyphenzin) exhibit AFA in acute regional myocardial ischemia (ARMI) [8][9][10]12].
MATERIALS AND METHODSExperiments were performed on anesthetized (sodium pentobarbital, 40 mg/kg, intravenously) cats (body weight 2.3-3.0 kg) of both sexes. Catheters were inserted in the right femoral vein for befol infusion and in the left femoral artery for measuring arterial pressure with an Elema-Simens electromanometer. Silver bipolar electrodes were sutured to the right ventricle of the heart after thoraco-and pericardiotomy. After a 10-min stabilization period, electric Department of Pharmacology, Kuban State Medical Academy, Krasnodar; Laboratory of Circulatory Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow threshold of ventricular fibrillation (ETVF) was determined by scanning the electrically vulnerable period of cardiac cycle (ascending portion of T wave) with a series of 20 rectangular direct current pulses of increasing intensity (pulse duration 4 msec, frequency 50 pulses/sec) until the appearance of ventricular fibrillation. Electrocardiogram (lead II) was recorded with an EKChT-02 electrocardiograph with a simultaneous record in an Attack-359 analyzer (Nihon Kohden). Direct electric countershock was delivered from a DI-3 apparatus. Acute regional myocardial ischemia was produced by occlusion of the descending branch of the left coronary artery between its upper and middle thirds. Befol was slowly infused using a Syringer Pump 355 (Sage Instruments). Three series of experiments (5 cats in each) were performed. In the first series, the effect of befol (5, 10, 15, and 20 mg/kg) on ETVF was studied in intact cats. In the second series, the effect of ARMI on ETVF was examined. In the third series, the effect of befol (20 mg/kg) on ETVF was assessed in cats with ARMI. The results were statistically processed using conventional methods [5].
RESULTSAt 5 and 10 mg/kg befol had no appreciable effect of ETVF (Table 1). A tendency toward an increase in ETVF was observed at 15 mg/kg, and a statistically significant rise of ETVF by 2.2 times was recorded