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Epicardial but not endocardial premature stimulation initiates ventricular tachyarrhythmia in canine in vitro model of long QT syndrome.

Abstract：

OBJECTIVES:To explore the mechanism, we tested the hypothesis that premature epicardial stimulation transiently increased the dispersion of repolarization leading to VT. BACKGROUND:Premature stimulation initiated ventricular tachycardia (VT) when applied to the epicardium but not to the endocardium in a canine model of long QT syndrome (LOTS). METHODS:We optically mapped action potentials (APs) on the cut-exposed transmural surfaces of isolated wedges of canine ventricular walls perfused with anemone toxin II (ATX-II), which produced type 3 LQTS with an asymmetrical transmural profile of repolarization that was earliest in the epicardium and latest in deep subendocardium. RESULTS:Earliest excitable epicardial stimulation triggered VT in 5 of 18 wedges receiving > or =5 nmol/L ATX-II by direct activation of epicardium, which delayed repolarization in the still refractory midmyocardium and further enhanced the dispersion of repolarization. These VTs were initiated 197 +/- 72 ms (n = 10) after the premature stimulation, from focal regions of earliest repolarization downstream to the steepest local spatial gradients of repolarization, and maintained by new focal activation and reentry. Transmural differences in the cycle lengths of activations altered conduction pathways and resulted in torsades de pointes-like polymorphic VT. In contrast, VTs were not initiated by endocardial stimulation at the same premature intervals or when ATX-II was < or =2.5 nmol/L. Failed VT initiation was associated with significantly lower maximum local gradient of repolarization. CONCLUSIONS:Heterogeneic repolarization in LQTS provides a transmural asymmetrical substrate for the earliest excitable epicardial, but not endocardial, stimulation to further delay midmyocardial repolarization and produce a steep spatial gradient of repolarization potential initiating torsades de pointes-like polymorphic VT.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Ueda N,Zipes DP,Wu J

doi

10.1016/j.hrthm.2004.07.019

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

684-94

issue

6

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(04)00421-7

journal_volume

1

pub_type

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