Effect of dofetilide on cardiac repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle.
Monophasic action potentials (MAP) were simultaneously recorded from the right ventricular (RV) apex (RVA) and the outflow tract (RVOT) before and after an infusion of dofetilide in 10 patients with documented ventricular tachycardia. After the drug infusion, the MAP duration (MAPd), repolarization time, and corrected QT interval were significantly prolonged during sinus rhythm, RV pacing, and RV extra stimulation. The prolongation of MAPd at 90% repolarization during RV pacing at a cycle length of 500 ms was 31 +/- 6 ms (13%) and 26 +/- 7 ms (11%) at RVA and RVOT, respectively. The ventricular effective refractory period was significantly prolonged by 33 +/- 9 ms (13%) and 22 +/- 7 ms (9%) at driving cycle lengths 600 and 500 ms, respectively. The MAPd shortening with decreasing diastolic time intervals was significantly diminished by dofetilide in early extra beats during RV extra stimulation, suggesting a relatively more pronounced effect of this drug at the early diastolic phase. The dispersion of repolarization, defined as the difference in MAPd between RVA and RVOT, and the activation time were not significantly changed. In conclusion, acute administration of dofetilide in patients with ventricular tachycardia significantly prolonged the time intervals of ventricular repolarization and refractoriness in a parallel fashion, without affecting intraventricular conduction. The effect of dofetilide on MAPd prolongation appeared not to be reverse use-dependent in this study in humans. These results verify the selective class III antiarrhythmic property of dofetilide and warrant further studies in patients.
Yuan
S
S
Department of Cardiology, University Hospital, Lund, Sweden.
Wohlfart
B
B
Rasmussen
H S
HS
Olsson
S
S
Blomström-Lundqvist
C
C
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003971:Diastole / Q000502:physiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D013449:Sulfonamides / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology*; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide