EFFECTS OF PLATELET-ACTIVATING-FACTOR ANTAGONISTS WEB-2086 AND BN-50730 ON DIGOXIN-INDUCED ARRHYTHMIAS

Effects of platelet-activating receptor antagonists WEB 2086 (1.0-30.0 mg . kg(-1) intravenously) and BN 50730 (10.0 . mg kg(-1) intravenous ly) alone or in combination with CGS 8515 (a specific 5-lipoxygenase i nhibitor, 0.3 mg . kg(-1) intravenously) and Dazmegrel(R) (a thromboxa ne synthase inhibitor, 1.0 mg . kg(-1) hr(-1) intravenous infusion) on digoxin-induced arrhythmias were investigated in anaesthetised guinea -pigs. EGG, mean arterial blood pressure, heart rate and arrhythmias w ere recorded, starting 30 min. before digoxin administration and conti nuing for 60 min. afterwards. WEB 2086 (10.0 mg . kg(-1) intravenously ) reduced the mortality rate and arrhythmia score significantly compar ed to the control values. However, in combination with CGS 8515, it di d not affect the mortality rate. BN 50730 (10.0 mg . kg(-1)) reduced t he incidence of ventricular fibrillation and also arrhythmia score. BN 50730 in combination with Dazmegrel(R) was reduced the arrhythmia sco re, incidence of ventricular fibrillation and mortality rate significa ntly, compared to control values. Digoxin-induced acute rise in mean a rterial blood pressure was not affected by any of drug treatment excep t WEB 2086 (10.0 mg . kg(-1)) in combination with CGS 8515. Heart rate values did not differ between groups. However, pressure-rate index wa s reduced by WEB 2086 alone or in combination with CGS 8615. Results s howed that although two different platelet-activating factor antagonis ts have different effects on the incidence of ventricular fibrillation and mortality, they improved the digoxin-induced arrhythmias when the y were used either separately or in combination with CGS 8515 or Dazme grel(R) by implicating that platelet-activating factor has a role on d igoxin-induced arrhythmias.