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

The aim of this study was to determine whether bisaramil-an antiarrhyt hmic compound under clinical investigation-influences the reperfusion- induced arrhythmias and biochemical parameters characterizing occlusio n-reperfusion-induced free-radical reactions. The left descending coro nary artery (LAD) was occluded for 60 min in anaesthetized dogs follow ed by one hour of reperfusion, Blood samples were taken at different t imes of the occlusion and reperfusion for the determination of plasma concentration of malondialdehyde (MDA), reduced (GSH) and oxidized glu tathione (GSSG); furthermore of the activity of catalase and superoxid e dismutase (SOD). Free-radical generating capacity of polymorph neutr ophil granulocytes (PMN) was also measured. At the end of the experime nts 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 2 mg kg(- 1) several minutes prior to the end of LAD-occlusion; then the adminis tration 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, how ever, VF was seen in three cases and no death was recorded. Bisaramil inhibited the elevation of the plasma concentration of MDA and GSSG du ring the reperfusion and abolished the decrease in the plasma concentr ation of GSH during the occlusion and reperfusion. The activity of SOD and catalase in plasma was much better preserved in the bisaramil-tre ated 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 sup ported the cardioprotective effect of bisaramil. The biochemical inves tigation of ischemic-reperfused myocardium showed that bisaramil promo ted 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 ischaem ia-reperfusion induced arrhythmias it has a special benefit in influen cing free-radical mediated damage leading to better preservation of me mbranes and to limitations of irreversible cell injuries. (C) 1996 The Italian Pharmacological Society