ELECTROPHYSIOLOGIC FEATURES OF TORSADES-DE-POINTES - INSIGHTS FROM A NEW ISOLATED RABBIT HEART MODEL

Torsades de Pointes in the Isolated Rabbit Heart. Introduction: The ex act electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particu lar arrhythmia exists. Methods and Results: In isolated rabbit hearts, TdP was induced by means of bradycardia in the presence of a high con centration of d-sotalol (10(-4) M) and shortly after lowering the conc entration of potassium and magnesium in the perfusate, Multiple simult aneous epicardial and endocardial monophasic action potentials (MAPs) and volume-conducted 12-lead ECGs were recorded. d-Sotalol prolonged r epolarization and increased dispersion of ventricular repolarization c ompared to baseline recordings. With the onset of low potassium and ma gnesium concentrations, repolarization was further prolonged and dispe rsion of repolarization was further increased followed by the occurren ce of early afterdepolarizations (EADs) in the majority of MAP recordi ngs, i.e., at both endocardial and epicardial locations of both ventri cles. Upon increase of EAD amplitude, triggered arrhythmias with TdP o f up to 42 beats ensued in 10 of 11 hearts studied, MAP duration at 90 % repolarization (APD(90)), dispersion of APD(90), and the incidence o f EADs as well as dispersion of the QT interval and T wave area were s ignificantly higher in beats triggering bigemini, couplets, or runs of TdP. Conclusion: TdP observed in this new isolated heart model was as sociated with markedly increased dispersion of ventricular repolarizat ion and the occurrence of EADs in multiple locations of the heart. TdP is initiated when the amplitude of an EAD reaches threshold for initi ation of the first beat of an episode.