Article date: August 1999
By: Tomokazu Watano, Yoshimitsu Harada, Kengo Harada, Noriyasu Nishimura, in Volume 127, Issue 8, pages 1846-1850
We investigated protective effects of KB‐R7943, a Na+/Ca2+ 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 μM) 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−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+channel inhibitor) and R56865 (Na+ and Ca2+ overload inhibitor) also suppressed the ouabain‐induced tonotropic effect and extra‐systole in isolated atria, but Hoe‐694 (Na+/H+ exchange inhibitor) or diltiazem (Ca2+ 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.
We investigated protective effects of KB‐R7943, a Na+/Ca2+ 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 μM) 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−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+channel inhibitor) and R56865 (Na+ and Ca2+ overload inhibitor) also suppressed the ouabain‐induced tonotropic effect and extra‐systole in isolated atria, but Hoe‐694 (Na+/H+ exchange inhibitor) or diltiazem (Ca2+ 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.
British Journal of Pharmacology (1999) 127, 1846–1850; doi:10.1038/sj.bjp.0702740
DOI: 10.1038/sj.bjp.0702740
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