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

Abstract

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.

Effects of Cyclosporin and Cremophor on Working Rat Heart and Incidence of Myocardial Lipid Peroxidation

“…Rats were anesthetized by diethyl ether. After administration of heparin, hearts were quickly re moved and perfused according to the 'working heart' model [5]. After 10 min of Langendorff perfusion, the left atria cannula was opened and left ventricular work was started under a filling pressure of 10 cm FLO and against a column of 80 cm HiO.…”

“…It was a modified Krebs-Henseleit solution containing (mmoi/I): NaCI 118; KC1 4.7; CaCl2 2.5; MgSO, 1.2; KFLPOj 1.2; glucose 11 [5]. All solutions were filtered through a 5-gm filter to remove any contaminating particles.…”

Effects of Aldosterone and Spironolactone on the Isolated Perfused Rat Heart

“…KC1 4.7, CaCl: 2.5, MgS04 1.2, K H ;P 0 4 1.2. and NaHCOi 25 mmol/1) equilibrated by OyCCT (at a ratio of 95:5 v/v)at 37 °C and maintained at pH 7.4. Glucose (5.5 mmol/1) was the only exoge nous substrate present in the saline [22], Coronary and aortic flows were measured every minute by collection of respective effluents into weighed tubes. Electrocar diographic tracings were continuously recorded using an Oxford cassette recorder: off-line reading and analy sis were performed employing an Elatec apparatus (Ela Médical.…”