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 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.