Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada syndrome model

Circulation. 2004 Jan 6;109(1):125-31. doi: 10.1161/01.CIR.0000105762.94855.46. Epub 2003 Dec 8.

Abstract

Background: Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited.

Methods and results: We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a supporter dog and examined the VT mechanism. Two plaque electrodes (35x30 mm) containing 96 bipolar electrodes were attached to the endocardium and epicardium. Saddleback and coved types of ST elevation in transmural ECG were induced by pilsicainide, a pure sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. Analysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated from a site with a short recovery time, suggesting that phase 2 reentry was its mechanism. The other 4 VTs in 4 preparations were induced by premature stimulation. Analysis of the activation sequences during VT revealed reentry between epicardium and endocardium or reentry around an arc of a functional block confined to epicardium or endocardium with bystander activation of the other.

Conclusions: Electrical heterogeneity in the recovery phase was induced in this experimental Brugada syndrome model, which can be a substrate for the development of phase 2 reentry and the subsequent reentry around an arc of the functional block, resulting in sustained VT.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Dogs
  • Electrocardiography* / drug effects
  • Female
  • In Vitro Techniques
  • Lidocaine / analogs & derivatives*
  • Male
  • Pinacidil
  • Potassium Channels / drug effects
  • Sodium Channel Blockers
  • Syndrome
  • Tachycardia, Ventricular / chemically induced*
  • Tachycardia, Ventricular / physiopathology*

Substances

  • Potassium Channels
  • Sodium Channel Blockers
  • Pinacidil
  • Lidocaine
  • pilsicainide