EFFECTS OF BISARAMIL ON CORONARY-OCCLUSION-REPERFUSION INJURY AND FREE-RADICAL-INDUCED REACTIONS

• Published in: Pharmacological research 1996-06, Vol.33 (6), p.327-336
• Main Authors: PARÓCZAI, MARGIT, ROTH, ELIZABETH, MATOS, GÁBOR, TEMES, GYULA, LANTOS, JÁNOS, KARPATI, EGON
• Format: Article
• Language: English
• Subjects: Animals; Anti-Arrhythmia Agents - therapeutic use; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; bisaramil; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Catalase - blood; Chlorobenzenes; Coronary Disease - complications; Coronary Disease - mortality; Coronary Disease - physiopathology; Dogs; Erythrocytes - enzymology; Female; Free Radicals - metabolism; Free Radicals - toxicity; Glutathione - blood; Hemodynamics - drug effects; Hemodynamics - physiology; lipid peroxidation; Male; Malondialdehyde - blood; myocardial ischaemia-reperfusion; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - physiopathology; Neutrophils - drug effects; Neutrophils - metabolism; Superoxide Dismutase - blood
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1996.0045

The aim of this study was to determine whether bisaramil—an antiarrhythmic compound under clinical investigation—influences the reperfusion–induced arrhythmias and biochemical parameters characterizing occlusion-reperfusion-induced free-radical reactions. The left descending coronary artery (LAD) was occluded for 60min in anaesthetized dogs followed by one hour of reperfusion. Blood samples were taken at different times of the occlusion and reperfusion for the determination of plasma concentration of malondialdehyde (MDA), reduced (GSH) and oxidized glutathione (GSSG); furthermore of the activity of catalase and superoxide dismutase (SOD). Free-radical generating capacity of polymorph neutrophil granulocytes (PMN) was also measured. At the end of the experiments heart tissue samples were excised from the injured areas and from the intact part of the left ventricular muscle. In tissue samples the concentrations of MDA and GSH and the activity of SOD were determined. Bisaramil was given as an i.v. bolus injection at a dose of 2mgkg −1several minutes prior to the end of LAD-occlusion; then the administration was repeated in the 30th minute of reperfusion. In the control group (10 dogs) ventricular fibrillation (VF) occurred in seven cases which resulted in death in three. In the bisaramil-treated group, however, VF was seen in three cases and no death was recorded. Bisaramil inhibited the elevation of the plasma concentration of MDA and GSSG during the reperfusion and abolished the decrease in the plasma concentration of GSH during the occlusion and reperfusion. The activity of SOD and catalase in plasma was much better preserved in the bisaramil-treated group then in the controls. Bisaramil significantly inhibited the increase of the superoxide-radical generating capacity of PMNs during the reperfusion. The data obtained from myocardial tissue samples supported the cardioprotective effect of bisaramil. The biochemical investigation of ischemic-reperfused myocardium showed that bisaramil promoted preservation of SOD-activity and of tissue glutathione. Results of this study clearly showed that bisaramil has a significant effect on ischemia-reperfusion injury. Besides its inhibitory effects on ischaemia-reperfusion induced arrhythmias it has a special benefit in influencing free-radical mediated damage leading to better preservation of membranes and to limitations of irreversible cell injuries.