Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome

Hiroshi Morita, Douglas P. Zipes, Shiho T. Morita, Jiashin Wu

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT). Objectives: The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome. Methods: Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 μmol/L), pinacidil (1.25-12.5 μmol/L), and terfenadine (2.0 μmol/L). Results: Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations. Conclusion: Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome.

Original languageEnglish (US)
Pages (from-to)66-74
Number of pages9
JournalHeart Rhythm
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Brugada syndrome
  • Intraventricular heterogeneity
  • Optical mapping
  • Repolarization
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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