Effect of Na super(+)/Ca super(2+) exchange inhibitor, KB-R7943 on ouabain-induced arrhythmias in guinea-pigs

We investigated protective effects of KB-R7943, a Na super(+)/Ca super(2+) exchange (NCX) inhibitor, on ouabain-induced tonotropy and arrhythmias in isolated whole atria and ouabain-induced changes in electrocardiogram (ECG) in the guinea-pig. KB-R7943 (10 and 30 mu M) suppressed the tonotropic effect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. The intravenous injection of KB-R7943 (1 and 3 mg kg super(-1)) significantly increased the doses of ouabain required to induce ventricular premature beats (VPB), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) in anaesthetized guinea-pigs. Lidocaine (Na super(+)channel inhibitor) and R56865 (Na super(+) and Ca super(2+) overload inhibitor) also suppressed the ouabain-induced tonotropic effect and extra-systole in isolated atria, but Hoe-694 (Na super(+)/H super(+) exchange inhibitor) or diltiazem (Ca super(2+) channel inhibitor) did not affect them. Lidocaine also increased the doses of ouabain required to induce VPB, VT, VF and CA in anaesthetized guinea-pigs. From these results, we conclude that KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX.