Differential class III antiarrhythmic effects of ambasilide and dofetilide at different extracellular potassium and pacing frequencies.
We studied the effect of two new class II antiarrhythmics, ambasilide and dofetilide, on the action potential duration (APD) of guinea pig right ventricular papillary muscle at different extracellular potassium concentrations ([K+e]) and pacing frequencies. Under normal [K+e], both drugs significantly prolonged APD90 (APD at 90% repolarization) at 0.5 Hz. The effect of ambasilide was well preserved at rapid pacing rates, independent of [K+e]. The effect of dofetilide was markedly reduced with increasing pacing rate, especially in high [K+e]. Therefore, ambasilide may be useful in treating tachyarrhythmias in normal, as well as in altered [K+e] conditions.
Gjini
V
V
Medizinische Klinik, Klinikum rechts der Isar, München, Germany.
Korth
M
M
Schreieck
J
J
Weyerbrock
S
S
Schömig
A
A
Schmitt
C
C
D000200:Action Potentials / Q000187:drug effects; D062365:Aminobenzoates / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*
D062365:Aminobenzoates; D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010627:Phenethylamines; D013449:Sulfonamides; C075113:ambasilide; C063533:dofetilide; D011188:Potassium