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(Circulation. 2004;109:125-131.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Mechanism of ST Elevation and Ventricular Arrhythmias in an Experimental Brugada Syndrome Model

Masaomi Kimura, MD; Takao Kobayashi, MD; Shingen Owada, MD; Keiichi Ashikaga, MD; Takumi Higuma, MD; Shingo Sasaki, MD; Atsushi Iwasa, MD; Shigeru Motomura, MD; Ken Okumura, MD

From the Second Department of Internal Medicine and Department of Pharmacology (S.M.), Hirosaki University School of Medicine, Hirosaki, Japan.

Correspondence to Ken Okumura, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki 036-8562, Japan. E-mail okumura{at}cc.hirosaki-u.ac.jp

Received January 7, 2003; de novo received June 25, 2003; revision received August 21, 2003; accepted August 22, 2003.

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 K_ATP 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.

Key Words: electrocardiography • mapping • reentry

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