Premium
Effect of Na + /Ca 2+ exchange inhibitor, KB‐R7943 on ouabain‐induced arrhythmias in guinea‐pigs
Author(s) -
Watano Tomokazu,
Harada Yoshimitsu,
Harada Kengo,
Nishimura Noriyasu
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702740
Subject(s) - ouabain , ventricular fibrillation , chemistry , medicine , sodium calcium exchanger , guinea pig , ventricular tachycardia , lidocaine , cardiology , endocrinology , sodium , pharmacology , calcium , anesthesia , organic chemistry
We investigated protective effects 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. KB‐R7943 (10 and 30 μ 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 −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 Ca 2+ overload inhibitor) also suppressed the ouabain‐induced tonotropic effect and extra‐systole in isolated atria, but Hoe‐694 (Na + /H + exchange inhibitor) or diltiazem (Ca 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.British Journal of Pharmacology (1999) 127 , 1846–1850; doi: 10.1038/sj.bjp.0702740