Europace Advance Access originally published online on August 29, 2008
Europace 2008 10(10):1218-1223; doi:10.1093/europace/eun248
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PRECLINICAL RESEARCH
Role of subendocardial Purkinje network in triggering torsade de pointes arrhythmia in experimental long QT syndrome
1 Downstate Medical Center, State University of New York, Brooklyn, NY, USA; 2 VA New York Harbor Healthcare System, 800 Poly Place, Brooklyn, NY 11209, USA
Aims: The present study addresses the controversy regarding the ‘primary’ role of the subendocardial Purkinje network in triggering torsade de pointes (TdP) ventricular tachyarrhythmia (VAs) in the long QT syndrome (LQTS).
Methods and results: We investigated the well-established canine anthopleurin-A (AP-A) surrogate model of LQT3 to study the role of the subendocardial Purkinje network in triggering VAs. Three-dimensional activation and repolarization patterns were analysed from unipolar extracellular electrograms utilizing 64 plunge needle electrodes. In 6 dogs, the animals were placed on cardiopulmonary bypass and chemical ablation of the endocardial Purkinje network was obtained using Lugol's solution. Spontaneous VAs consistently developed in response to AP-A infusion and were triggered by a subendocardial focal activity acting on a substrate of spatial three-dimensional dispersion of repolarization. Endocardial ablation was considered successful by the development of complete atrioventricular block in the absence of ventricular escape rhythm. Following endocardial ablation spontaneous VAs were no longer observed. However, an appropriately coupled premature stimulus consistently induced re-entrant VAs.
Conclusion: The present study strongly suggests that in the LQTS, focal activity generated in subendocardial Purkinje tissue is the primary, if not the only, trigger for TdP VAs by acting on a substrate of three-dimensional dispersion of myocardial repolarization to induce re-entrant excitation.
Key Words: Arrhythmias, Long QT syndrome, Mapping, Repolarization, Early afterdepolarizations, Re-entry, Ablation
* Corresponding author. Tel: +1 718 630 3740; Fax: +1 212 570 9714. E-mail address: nelsherif{at}aol.com
Manuscript submitted 7 May 2008. Accepted after revision 12 August 2008.
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