EFFECTS OF A LEUKOTRIENE-D(4) RECEPTOR ANTAGONIST, L-648,051, AND A DUAL INHIBITOR LYPOXYGENASE AND CYCLOOXYGENASE, BW-755C, ON DIGOXIN-INDUCED ARRHYTHMIAS IN GUINEA-PIGS
S. Gok et N. Banoglu, EFFECTS OF A LEUKOTRIENE-D(4) RECEPTOR ANTAGONIST, L-648,051, AND A DUAL INHIBITOR LYPOXYGENASE AND CYCLOOXYGENASE, BW-755C, ON DIGOXIN-INDUCED ARRHYTHMIAS IN GUINEA-PIGS, Archives internationales de pharmacodynamie et de therapie, 321, 1993, pp. 72-80
In this study, we investigated the effects of leukotrienes on digitali
s-induced arrhythmias in guinea-pigs, utilizing a dual inhibitor of ly
poxygenase and cyclooxygenase, BW-755C, and a leukotriene D4 receptor
antagonist, L-648,051. Guinea-pigs, anaesthetized with urethane (1.5 g
/kg, intraperitoneally) and breathing spontaneously, received an intra
venous injection of BW-755C (5, 10 and 20 mg/kg) or L-648,051 (5 and 1
0 mg/kg) 15 min prior to digoxin. Digitalis arrhythmias were induced b
y a 50 mug/kg intravenous bolus injection, followed, 15 min later, by
a 400 mug/kg/hr intravenous infusion. Compared with the control group,
L-648,051 (5 mg/kg) significantly increased the digoxin dose causing
ventricular tachycardia and mortality. BW-755C (5 and 10 mg/kg, but no
t 20 mg/kg) significantly increased the digoxin dose causing mortality
. Both L-648,051 (5 mg/kg) and BW-755C (10 mg/kg) significantly preven
ted the incidence of ventricular fibrillation. At a higher dose (20 mg
/kg), BW-755C caused a more rapid development of ventricular fibrillat
ion and mortality than in other doses. These data suggest that inhibit
ors of lypoxygenase and leukotriene receptor antagonists may have prot
ective effects and that endogenously released leukotrienes may play an
important role in digoxin-induced arrhythmias in guinea-pigs.