Effects of cyclooxygenase and lipoxygenase inhibitors on digoxin-induced arrhythmias and haemodynamics in guinea-pigs.

Effects of cyclooxygenase and lipoxygenase inhibitors of digoxin-induced arrhythmias and haemodynamics were studied in guinea-pigs. ECG, mean arterial blood pressure heart rate, pressure rate index and arrhythmias were recorded, starting 15 min before digoxin administration and continuing for 30 min afterwards. The cyclooxygenase inhibitor aspirin (50 mg kg-1) and the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (0.25-10.0 mg kg-1) were found to produce a significant protection against the arrhythmias, whereas aspirin (100 mg kg-1) and CGS 8515 were found to be ineffective. SK&F 104 353, a potent and selective peptidoleukotriene receptor antagonist significantly attenuated the arrhythmias and mortality in a dose-dependent manner. It is concluded that production of both cyclooxygenase and lipoxygenase metabolites could favour the occurrence and/or the maintenance of digoxin-induced cardiac toxicity.