Prolonged action potential duration and positive inotropy induced by the novel class III antiarrhythmic agent H 234/09 (Almokalant) in isolated human ventricular muscle.
The electromechanical properties of H 234/09 (Almokalant), a novel class III antiarrhythmic agent, was examined in isolated human ventricular muscle strips excised from patients undergoing mitral valve replacement. Using transmembrane microelectrode recording techniques, we demonstrated that H 234/09 markedly prolonged the action potential duration (APD) without affecting the maximal rate of depolarization or action potential amplitude. At 75 and 90% repolarization APD was prolonged to a similar extent, whereas the lengthening at 50% repolarization was somewhat less marked. In isometrically contracting muscle strips, H 234/09 increased peak developed force and its maximal rate of rise (dF/dt) and fall (-dF/dt) in a concentration-dependent manner, whereas time to peak developed force was unaltered. We conclude from these studies that H 234/09 is a class III agent in human ventricular muscle and that the class III effect is linked with a positive inotropic response.
Carlsson
L
L
Preclinical Research and Development, Astra Hässle, Mölndal, Sweden.
Abrahamsson
C
C
Almgren
O
O
Lundberg
C
C
Duker
G
G
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; C074334:almokalant; D002118:Calcium