Rate-independent effects of the new class III antiarrhythmic agent ambasilide on transmembrane action potentials in human ventricular endomyocardium

S. Weyerbrock, J. Schreieck, M. Karch, M. Overbeck, H. Meisner, B. Kemkes, A. Schomig, C. Schmitt

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The electrophysiologic effects of ambasilide, a new class III antiarrhythmic drug reported to be a nonselective blocker of both components (I(Kr) and I(Ks)) of the delayed-rectifier potassium current (I(K)) and ether repolarizing potassium currents (I(tol), I(so)), were studied in specimens of left ventricular endomyocardium of human hearts obtained from 10 patients undergoing either heart transplantation (n = 4) or mitral valve replacement (n = 6). We recorded transmembrane action potential (TAP) characteristics at different stimulation frequencies (0.5, 1, 1.5, and 2 Hz) and with different dosages of ambasilide (1, 10, and 50 μM) by using conventional microelectrode techniques. Beginning at a concentration of 10 μM ambasilide, the TAP duration at 90% repolarization (TAPD90) was significantly prolonged and independent of stimulation frequency with a mean percentage prolongation of 18% at 10 μM and 30% at 50 μM ambasilide. TAP duration at 50% repolarization was not significantly prolonged except for 10 μM ambasilide at 0.5 Hz (17%; p < 0.05). The frequency-independent action potential (AP) prolongation by ambasilide in human ventricular endomyocardium indicates that a nonselective block of repolarizing potassium currents seems to be more favorable than a selective block of I(Kr).

Original languageEnglish
Pages (from-to)571-575
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume30
Issue number5
DOIs
StatePublished - 1997

Keywords

  • Ambasilide
  • Delayed rectifier K current
  • Human ventricular endomyocardium
  • Transmembrane action potential

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