S. Gok et al., POSSIBLE CONTRIBUTION OF LEUKOTRIENES IN THE ARRHYTHMOGENIC EFFECTS OF DIGOXIN ON ISOLATED GUINEA-PIG HEARTS, Pharmacology, 57(5), 1998, pp. 279-284
The effect of a leukotriene D-4 (LTD4) receptor antagonist, L-648,051,
was investigated in digoxin-induced cardiac toxicity in isolated guin
ea-pig hearts (Langendorff preparation). Digoxin infusion (25 mu g.ml(
-1), 0.5 ml.min(-1)) increased perfusion pressure and contractile forc
e initially, but decreased them later. The onset of first ventricular
premature beats (VPBs) matched the increase phase, but the decrease ph
ase was accompanied by ventricular tachycardia (VT) and fibrillation (
VF). In the presence of L-648,051 (5 mu mol.l(-1)), the initial phase
was similar to that observed with digoxin alone, but the marked reduct
ion was inhibited. This drug increased the concentration of digoxin re
quired for VBSs and cardiac arrest, but it could not prevent the forma
tion of VT and VF. The duration of VT was significantly decreased by L
648,051. It is concluded that the leukotriene receptor antagonist migh
t have beneficial effects on digoxin-induced arrhythmias. Whether this
effect depends on direct or indirect actions is uncertain.