1 We investigated protective e ects of KB-R7943, a Na + /Ca 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. 2 KB-R7943 (10 and 30 mM) suppressed the tonotropic e ect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. 3 The intravenous injection of KB-R7943 (1 and 3 mg kg 71 ) signi®cantly increased the doses of ouabain required to induce ventricular premature beats (VPB), ventricular tachycardia (VT), ventricular ®brillation (VF) and cardiac arrest (CA) in anaesthetized guinea-pigs. 4 Lidocaine (Na + channel inhibitor) and R56865 (Na + and Ca 2+ overload inhibitor) also suppressed the ouabain-induced tonotropic e ect and extra-systole in isolated atria, but Hoe-694 (Na + /H + exchange inhibitor) or diltiazem (Ca 2+ channel inhibitor) did not a ect them. 5 Lidocaine also increased the doses of ouabain required to induce VPB, VT, VF and CA in anaesthetized guinea-pigs. 6 From these results, we conclude that KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX.

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