Published Online
on April 12, 2004

A more recent version of this article appeared on May 4, 2004

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Submitted on August 20, 2003
Revised on December 30, 2003
Accepted on January 23, 2004

Epicardial Activation of Left Ventricular Wall Prolongs QT Interval and Transmural Dispersion of Repolarization. Implications for Biventricular Pacing

Jeffrey M. Fish DVM, José M. Di Diego MD, Vladislav Nesterenko PhD, and Charles Antzelevitch PhD^*

From the Masonic Medical Research Laboratory, Utica, NY.

^* To whom correspondence should be addressed. E-mail: ca{at}mmrl.edu.

Background--Epicardial pacing of the left ventricle (LV) has been shown to prolong the QT interval and predispose to the development of torsade de pointes arrhythmias. The present study examines the cellular basis for QT prolongation and arrhythmogenesis after reversal of the direction of activation of the LV wall.

Methods and Results--A transmural ECG and transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial cells of arterially perfused canine LV wedge preparations. QT interval increased from 297.6±3.9 to 314.0±5.7 ms (n=12; P<0.001) and transmural dispersion of repolarization (TDR) increased from 35.5±5.2 to 70.3±6.2 ms (n=12; P<0.001) as pacing was shifted from endocardium to epicardium. Conduction time between M and epicardial cells increased from 12.1±1.2 to 24.2±1.5 ms (n=12; P<0.001). Amplification of TDR was further accentuated in the presence of rapidly activating delayed rectifier potassium current blockers (E-4031 and cisapride), increasing from 50.5±7.6 to 86.1±6.2 ms (n=8; P<0.01). Torsade de pointes arrhythmias could be induced during epicardial, but not endocardial, pacing of LV in the presence of rapidly activating delayed rectifier potassium current blockade.

Conclusions--Reversal of the direction of activation of the LV wall, as occurs during biventricular pacing, leads to a prominent increase in QT and TDR as a result of earlier repolarization of epicardium and delayed activation and repolarization of the midmyocardial M cells. The increase in TDR creates the substrate for the development of torsade de pointes under long-QT conditions.

Key words: electrocardiography • torsade de pointes • heart failure • pacemakers • electrophysiology

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