EFFECTS OF A LIPOXYGENASE INHIBITOR ON DIGOXIN-INDUCED CARDIAC-ARRHYTHMIAS IN THE ISOLATED-PERFUSED GUINEA-PIG HEART

1. The effects of a lipoxygenase inhibitor, BW A4C, on digoxin-induced arrhythmias and cardiac dynamics (contractile force, perfussion press ure, heart rate) were investigated in Langendorff perfused isolated gu inea pig hearts. In the control group, arrhythmias were induced by 25 mu g/ml digoxin at a perfusion rate of 0.5 ml/min. In the treated grou ps, BW A4C (1 and 0.3 mu M) perfused continuously from 15 min prior to digoxin until cardiac arrest occurred. Digoxin exposure (mu g/g wet w eight of heart) for the occurrence of arrhythmias and cardiac arrest w ere the parameters evaluated to assess cardiotoxicity. 2. Digoxin caus ed a marked increase in leukotriene Bq release in the coronary effluen t, and was collected during tachyarrhythmias. BW A4C markedly inhibite d the digoxin-induced elevation of LTB4. 3. BW A4C (1 and 0.3 mu M) di d not prevent the onset of ventricular fibrillation and ventricular ta chycardia despite a slight delay in the occurrence of ventricular fibr illation and cardiac arrest at the 0.3 mu M concentration. 4. Contract ile force increased significantly after digoxin infusion which was con comitant with the time of onset of arrhythmias. In the presence of BW A4C, the contractile force increased, but not significantly. Perfusion pressure increased initially after digoxin infusion in the absence an d the presence of BW A4C, but not significantly. 5. These findings sho w that the lipoxygenase inhibitor lacked any protective action on digo xin-induced arrhythmias despite its effective suppression of digoxin-i nduced elevation of LTB4 in coronary effluent. (C) 1997 Elsevier Scien ce Inc.