Effects of the new class III antiarrhythmic drug dofetilide on the atrial and ventricular intracardiac monophasic action potential in patients with angina pectoris.
The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs.
Sedgwick
M L
ML
Department of Medical Cardiology, Royal Infirmary, Glasgow, U.K.
Dalrymple
I
I
Rae
A P
AP
Cobbe
S M
SM
D000200:Action Potentials / Q000187:drug effects; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D016275:Atrial Function / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D004311:Double-Blind Method; D004562:Electrocardiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000627:therapeutic use*; D011930:Reaction Time / Q000187:drug effects; D012032:Refractory Period, Electrophysiological; D013449:Sulfonamides / Q000627:therapeutic use*; D016276:Ventricular Function / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide