Effects of thromboxane synthetase inhibitor (UK 38,485) and thromboxane receptor antagonist (ICI 185,282) on digoxin-induced arrhythmias in anaesthetized guinea-pigs.

1. Increased local thromboxane (Tx) formation has been considered to be a contributing factor in digitalis-induced arrhythmias. 2. A potent Tx synthetase inhibitor (TxSI), UK 38,485 (0.1, 1.0 or 10.0 mg/kg per h, administered intravenously) and a Tx receptor antagonist (TxRA), ICI 185,282 (1, 2 or 10 mg/kg bolus and 1, 2 or 10 mg/kg per h, administered intravenously) were tested for their ability to reduce digoxin-induced arrhythmias in anaesthetized guinea-pigs. 3. Electrocardiograms, mean blood pressure, heart rate and arrhythmias were recorded, starting 30 min before digoxin administration and continued for 60 min afterwards. 4. ICI 185,282, at the doses used, significantly delayed the time of onset of arrhythmias, and reduced the incidence of ventricular fibrillation, mortality and arrhythmia score. In contrast, UK 38,485 was found to be effective on all measured variables only at the dose rate of 1.0 mg/kg per h, except for time required for the development of arrhythmias. These protective effects of both TxSI and TxRA were not found to be dose-dependent. 5. Arterial blood pressure and heart rate changes caused by either UK 38,485 or ICI 185,282 infusions did not have any marked effects on digoxin-induced arrhythmias. 6. These data suggest that endogenously released TxA2 and prostaglandin endoperoxides may play an important role in digoxin-induced arrhythmias in guinea-pigs.