Effects of platelet-activating receptor antagonists
WEB 2086 (1.0-30.0 mg.kg-1 intravenously) and
BN 50730 (10.0 mg.kg-1 intravenously) alone or in combination with
CGS 8515 (a specific
5-lipoxygenase inhibitor, 0.3 mg.kg-1 intravenously) and
Dazmegrel (a
thromboxane synthase inhibitor, 1.0 mg.kg-1.hr-1
intravenous infusion) on
digoxin-induced arrhythmias were investigated in anaesthetised guinea-pigs. ECG, mean arterial blood pressure, heart rate and arrhythmias were recorded, starting 30 min. before
digoxin administration and continuing for 60 min. afterwards.
WEB 2086 (10.0 mg.kg-1 intravenously) reduced the mortality rate and
arrhythmia score significantly compared to the control values. However, in combination with
CGS 8515, it did not affect the mortality rate.
BN 50730 (10.0 mg.kg-1) reduced the incidence of
ventricular fibrillation and also
arrhythmia score.
BN 50730 in combination with
Dazmegrel was reduced the
arrhythmia score, incidence of
ventricular fibrillation and mortality rate significantly, compared to control values.
Digoxin-induced acute rise in mean arterial blood pressure was not affected by any of drug treatment except
WEB 2086 (10.0 mg.kg-1) in combination with
CGS 8515. Heart rate values did not differ between groups. However, pressure-rate index was reduced by
WEB 2086 alone or in combination with CGS 8615. Results showed that although two different
platelet-activating factor antagonists have different effects on the incidence of
ventricular fibrillation and mortality, they improved the
digoxin-induced arrhythmias when they were used either separately or in combination with
CGS 8515 or
Dazmegrel by implicating that
platelet-activating factor has a role on
digoxin-induced arrhythmias.