Analysis of Unipolar Electrograms in Rabbit Heart Demonstrated the Key Role of Ventricular Apicobasal Dispersion in Arrhythmogenicity

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• 作者：Nicolas Guérard (1)
  Pierre Jordaan (2)
  Bérengère Dumotier (1)
  
• 关键词：Torsade de Pointes ; Repolarization reserve ; Transmural ; Apex ; to ; base dispersion of repolarization ; Rabbit heart ; Arrhythmogenicity
• 刊名：Cardiovascular Toxicology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：4
• 页码：316-328
• 全文大小：1,219 KB
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• 作者单位：Nicolas Guérard (1)
  Pierre Jordaan (2)
  Bérengère Dumotier (1)
  
  1. Novartis Institutes for Biomedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstrasse 141, WKL.136.176, 4057, Basel, Switzerland
  2. Drug Safety and Epidemiology, Novartis Pharma AG, Werk Klybeck, Basel, Switzerland
  
• ISSN：1559-0259

文摘

Reduced repolarization reserve and increased transmural dispersion of repolarization (TDR) are known risk factors for Torsade de Pointes development, but less is known about the role of apex-to-base (apicobasal) repolarization in arrhythmogenesis. 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. About 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. 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.