Possible contribution of leukotrienes in the arrhythmogenic effects of digoxin on isolated guinea-pig hearts

The effect of a leukotriene D-4 (LTD4) receptor antagonist, L-648,051, was investigated in digoxin-induced cardiac toxicity in isolated guinea-pig hearts (Langendorff preparation). Digoxin infusion (25 mu g.ml(-1), 0.5 ml.min(-1)) increased perfusion pressure and contractile force initially, but decreased them later. The onset of first ventricular premature beats (VPBs) matched the increase phase, but the decrease phase 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 reduction was inhibited. This drug increased the concentration of digoxin required for VBSs and cardiac arrest, but it could not prevent the formation of VT and VF. The duration of VT was significantly decreased by L648,051. It is concluded that the leukotriene receptor antagonist might have beneficial effects on digoxin-induced arrhythmias. Whether this effect depends on direct or indirect actions is uncertain.