Key result
KB-R7943 suppressed ouabain-induced tonotropy and significantly increased the doses of ouabain required to induce ventricular arrhythmias in guinea-pigs.
Why the study?
Does KB-R7943 prevent ouabain-induced arrhythmias in guinea-pig models?
Does KB-R7943 prevent ouabain-induced arrhythmias in guinea-pig models?
KB-R7943 suppresses ouabain-induced arrhythmias in guinea-pig models, likely through inhibition of reverse-mode Na+/Ca2+ exchange.
Supports NCX inhibition in arrhythmia models; leaves open any human translation or clinical testing.
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. 2. KB-R7943 (10 and 30 microM) suppressed the tonotropic effect 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-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. 4. 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. 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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Watano et al. (1999) studied Ouabain-induced arrhythmias. KB-R7943 was evaluated on Ouabain-induced tonotropy and arrhythmias (onset time of extra-systole, doses of ouabain required to induce VPB, VT, VF, CA). KB-R7943 suppressed ouabain-induced tonotropy and significantly increased the doses of ouabain required to induce ventricular arrhythmias in guinea-pigs.
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