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Analysis of unipolar electrograms in rabbit heart demonstrated the key role of ventricular apicobasal dispersion in arrhythmogenicity

Guerard, Nicolas and Jordaan, Pierre and Dumotier, Berengere (2014) Analysis of unipolar electrograms in rabbit heart demonstrated the key role of ventricular apicobasal dispersion in arrhythmogenicity. jOURNAL OF CARDIOVASCULAR TOXICOLOGY.

Abstract

INTRODUCTION: Reduced repolarization reserve and increased transmural dispersion of repolarization (TDR) are known risk factors for Torsade de Pointes (TdP) development, but less is known about the role of apex-to-base (apicobasal) repolarization in arrhythmogenesis.
METHODS: Three needles were inserted in rabbit left ventricle to record unipolar electrograms from endocardium to epicardium and base to apex. Total repolarization interval (TRI) and peak-to-end repolarization interval (Tp) were assessed after quinidine (n=6) and d,l-sotalol (n=6) perfusion in combination with the IKs inhibitor chromanol 293B.
RESULTS: 30 µM d,l-sotalol increased TRI and Tp more at the base (TRI +40 ± 4 %; Tp +89 ± 11 %) relative to the apex (TRI +28 ± 3 %, Tp +30 ± 8 %). Similar results were obtained with quinidine: TRI and Tp increased more at the base compared to the apex. No significant differences were recorded from the endocardium to the epicardium.
DISCUSSION: Our results show that combined IKr + IKs block prolonged TRI and Tp significantly more at the ventricular base than at the apex, in the absence of transmural dispersion of refractoriness. Regional changes in TRI and Tp indicate the contribution of apicobasal dispersion to arrhythmogenicity compared to TDR in a rabbit heart model.

Item Type: Article
Keywords: Torsade de Pointes, Repolarization reserve, transmural, apex-to-base dispersion of repolarization, rabbit heart, arrhythmogenicity
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21459

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