Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model.
BACKGROUND
The exact electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particular arrhythmia exists.


RESULTS
In isolated rabbit hearts, TdP was induced by means of bradycardia in the presence of a high concentration of d-sotalol (10(-4) M) and shortly after lowering the concentration of potassium and magnesium in the perfusate. Multiple simultaneous epicardial and endocardial monophasic action potentials (MAPs) and volume-conducted 12-lead ECGs were recorded. d-Sotalol prolonged repolarization and increased dispersion of ventricular repolarization compared to baseline recordings. With the onset of low potassium and magnesium concentrations, repolarization was further prolonged and dispersion of repolarization was further increased followed by the occurrence of early afterdepolarizations (EADs) in the majority of MAP recordings, i.e., at both endocardial and epicardial locations of both ventricles. Upon increase of EAD amplitude, triggered arrhythmias with TdP of up to 42 beats ensued in 10 of 11 hearts studied. MAP duration at 90% repolarization (APD90), dispersion of APD90, and the incidence of EADs as well as dispersion of the QT interval and T wave area were significantly higher in beats triggering bigemini, couplets, or runs of TdP.


CONCLUSIONS
TdP observed in this new isolated heart model was associated with markedly increased dispersion of ventricular repolarization and the occurrence of EADs in multiple locations of the heart. TdP is initiated when the amplitude of an EAD reaches threshold for initiation of the first beat of an episode.
Zabel
M
M
Department of Medicine, J.W. Goethe University, Frankfurt, Germany.
Hohnloser
S H
SH
Behrens
S
S
Li
Y G
YG
Woosley
R L
RL
Franz
M R
MR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D011188:Potassium / Q000502:physiology; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology; D016171:Torsades de Pointes / Q000188:drug therapy / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D013015:Sotalol; D008274:Magnesium; D011188:Potassium