Antiarrhythmic Properties of Antidepressant Drugs after Coronary Artery Occlusion and Reperfusion in Rats

Bril, Antoine; Rochette, Luc

doi:10.1159/000138342

Cited by 7 publications

(3 citation statements)

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“…How ever, without any effect on the total duration of reperfusion-induced arrhythmias, tianep tine reduced the number of hearts showing long-lasting ventricular arrhythmias. The an tiarrhythmic effect of amitriptyline and mian serin against reperfusion-induced arrhyth mias provides confirmation of the protective activity of these two compounds in arrhyth mias related to ischemia and reperfusion [13][14][15], Although mianserin and amitriptyline improved the recovery of cardiac function during reperfusion, amitriptyline was the only compound which exhibited a marked cardiodepressant activity in our study. Amitrip tyline (10 pmol/1) induced a pronounced re duction in the efficacy of the hearts both dur ing preischcmic and ischemic periods.…”

Section: Discussionsupporting

confidence: 75%

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Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation

Bril¹,

Abadie²,

A³

et al. 1993

Pharmacology

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Tricyclic antidepressant drugs may affect the cardiovascular system, principally in patients with preexisting cardiac disease. The present study was undertaken to compare the effects of amitriptyline and mianserin with those of tianeptine, an atypical tricyclic antidepressant drug, in rat isolated working heart subjected to a local myocardial ischemia. Coronary, aortic and cardiac flows, and heart rate remained stable during the whole pre-ischemic period in control hearts. Ligation of the left main coronary artery induced a 50% decrease in coronary, aortic and cardiac flow without any change in heart rate. Reperfusion was characterized by the occurrence of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) and by a marked reduction in cardiodynamic parameters. Amitriptyline (1 and 10 μmol/l) and mianserin (1 and 10 μmol/l) exhibited an anti-arrhythmic activity against reperfusion arrhythmias. Tianeptine (1 and 10 μmol/l) was not able to reduce the incidence of reperfusion arrhythmias. Although tianeptine did not change heart rate, mianserin and amitriptyline induced a bradycardia. Mianserin and amitriptyline improved the cardiac recovery of cardiac function during reperfusion. The cardiodynamic parameters (coronary, aortic and cardiac flows) were not altered by tianeptine during the preischemic period. Furthermore, these parameters were similar to those observed in the control group both during ischemia and reperfusion. The beneficial effects of amitriptyline and mianserin observed in the setting of myocardial reperfusion were not associated with a reduced lipoperoxidation investigated by using an in vitro model in the presence or absence of a free-radical-generating system. The results of the present study indicate that the pronounced antiarrhythmic activities of mianserin and amitriptyline cannot be explained by an antiperoxidative action of these drugs.

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Section: Discussionsupporting

confidence: 75%

“…The effects observed with tianeptine may be compared to those of its structurally re lated compound, amineptine, which did not show any effect on both ventricular arrhyth mias and action potential parameters [14,15,22], However, the electrophysiological activ ity of tianeptine remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation

Bril¹,

Abadie²,

A³

et al. 1993

Pharmacology

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“…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].…”

Section: Abstract: Befol; Ventricular Fibrillation; Ischemia Treatmentmentioning

confidence: 99%

Effect of befol on the electric threshold of ventricular fibrillation

et al. 1997

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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

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Desipramine prevents cardiac gap junction uncoupling

Jozwiak¹,

Dietze

Grover

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Antiarrhythmic Properties of Antidepressant Drugs after Coronary Artery Occlusion and Reperfusion in Rats

Cited by 7 publications

References 25 publications

Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation

Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation

Effect of befol on the electric threshold of ventricular fibrillation

Desipramine prevents cardiac gap junction uncoupling

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Antiarrhythmic Properties of Antidepressant Drugs after Coronary Artery Occlusion and Reperfusion in Rats

Cited by 7 publications

References 25 publications

Absence of Relationship between Antiarrh&gamma;thmic Effects of Antidepressant Drugs and Lipid Peroxidation

Absence of Relationship between Antiarrh&gamma;thmic Effects of Antidepressant Drugs and Lipid Peroxidation

Effect of befol on the electric threshold of ventricular fibrillation

Desipramine prevents cardiac gap junction uncoupling

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Product

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Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation

Absence of Relationship between Antiarrhγthmic Effects of Antidepressant Drugs and Lipid Peroxidation