TY - JOUR
T1 - Rate-independent effects of the new class III antiarrhythmic agent ambasilide on transmembrane action potentials in human ventricular endomyocardium
AU - Weyerbrock, S.
AU - Schreieck, J.
AU - Karch, M.
AU - Overbeck, M.
AU - Meisner, H.
AU - Kemkes, B.
AU - Schomig, A.
AU - Schmitt, C.
PY - 1997
Y1 - 1997
N2 - 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).
AB - 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).
KW - Ambasilide
KW - Delayed rectifier K current
KW - Human ventricular endomyocardium
KW - Transmembrane action potential
UR - http://www.scopus.com/inward/record.url?scp=0030734281&partnerID=8YFLogxK
U2 - 10.1097/00005344-199711000-00006
DO - 10.1097/00005344-199711000-00006
M3 - Article
C2 - 9388038
AN - SCOPUS:0030734281
SN - 0160-2446
VL - 30
SP - 571
EP - 575
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5
ER -