Effects of bepridil on ventricular depolarization and repolarization of rabbit isolated hearts with particular reference to its possible proarrhythmic properties.
1. Effects of bepridil on ventricular depolarization and repolarization sequences were examined in rabbit Langendorff-perfused hearts. 2. In distant bipolar electrograms (DBEs), bepridil, 10(-6) M, caused a significant prolongation of QT intervals. At 10(-5) M, the QT prolongation was further enhanced, and a significant prolongation of QRS duration was also observed. Polymorphous ventricular tachycardia was frequently induced by a single premature stimulus at the higher concentration. 3. In epicardial electrograms recorded through modified bipolar electrodes, bepridil, 10(-6) M, prolonged the interval from the peak negative deflection of the QRS complex to the apex of the T wave (Q-aT), which corresponded to the intracellular action potential duration at 90% repolarization (APD90). The Q-aT prolongation was larger in the base than in the apex, resulting in a marked distortion and dispersion of repolarization. The epicardial activation sequence was unaffected. 4. At 10(-5) M bepridil, the dispersion of repolarization was much more enhanced by activation delay in the epicardial surface. 5. These findings suggest that bepridil causes regionally different lengthening of APD in ventricular muscle leading to an increase in temporal dispersion of repolarization, and that this dispersion may be inducive for re-entrant arrhythmias when accompanied by slow conduction at toxic doses.
Osaka
T
T
Department of Circulation and Respiration, Nagoya University, Japan.
Kodama
I
I
Toyama
J
J
Yamada
K
K
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D015764:Bepridil; D004569:Electroencephalography; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents; D011759:Pyrrolidines / Q000494:pharmacology*; D016276:Ventricular Function
D009467:Neuromuscular Depolarizing Agents; D011759:Pyrrolidines; D015764:Bepridil