Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent.
The effect of intravenous tedisamil (0.3 mg.kg-1), a newly developed potassium-blocking agent, on ventricular repolarization was studied in 10 patients (three women, seven men; mean age 53 +/- 8 years) with coronary artery disease (stenoses < or = 60%). Left ventricular monophasic action potentials, effective refractory periods and surface electrocardiograms were recorded during sinus rhythm and during constant atrial pacing at cycle lengths of 600, 500 and 400 ms. Under tedisamil there was a 12% reduction of heart rate and in parallel a prolongation of QTc interval (+10%) and left ventricular monophasic action potential duration (+16% at 90% repolarization). QRS duration remained unchanged. Tedisamil increased the duration of monophasic action potentials during constant atrial pacing, indicating a direct prolongation effect on left ventricular repolarization independent of sinus node activity. By increasing the atrial pacing rate this prolonging effect diminished. Left ventricular effective refractory periods also increased in a frequency-dependent fashion with a greater prolongation effect at long cycle lengths as compared to short cycle lengths. The ratio between effective refractory period and monophasic action potential duration, however, remained constant, independent of heart rate. We conclude that tedisamil is bradycardiac at the dose tested and has a reverse use dependent prolongation effect on left ventricular repolarization and refractoriness. The electrophysiologic profile is consistent with a class III antiarrhythmic classification.
Bargheer
K
K
Department of Cardiology, Hannover Medical School, Germany.
Bode
F
F
Klein
H U
HU
Trappe
H J
HJ
Franz
M R
MR
Lichtlen
P R
PR
D000200:Action Potentials / Q000187:drug effects; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000503:physiopathology*; D003521:Cyclopropanes / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; D026902:Potassium Channel Blockers; C059921:tedisamil