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(Circulation. 2003;108:882.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Tissue Discontinuities Affect Conduction Velocity Restitution

A Mechanism by Which Structural Barriers May Promote Wave Break

Richard Derksen, MD; Harold V.M. van Rijen, PhD; Ronald Wilders, PhD; Sara Tasseron, RT; Richard N.W. Hauer, MD; Willem L.C. Rutten, PhD; Jacques M.T. de Bakker, PhD

From the Heart Lung Center Utrecht (R.D., R.N.W.H.) and the Department of Medical Physiology (H.V.M.v.R.), University Medical Center, Utrecht; the Experimental and Molecular Cardiology Group (S.T.) and the Department of Physiology (R.W.), Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam; the Institute for Biomedical Technology, University of Twente (W.L.C.R.), Enschede; and the Interuniversity Cardiology Institute of the Netherlands (J.M.T.d.B.), Utrecht, Netherlands.

Correspondence to Jacques M.T. de Bakker, PhD, Department of Experimental Cardiology, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. E-mail j.m.debakker{at}amc.uva.nl

Received January 23, 2003; revision received April 17, 2003; accepted April 18, 2003.

Background— The mechanism by which structural barriers promote wave break and fibrillation is unclear. Conduction velocity (CV) restitution is an important determinant of wave break. Abnormal CV restitution is associated with ventricular fibrillation in patients with heart disease and arises preferentially in fibrotic myocardium. We hypothesize that tissue discontinuities imposed by structural barriers cause abnormal CV restitution.

Methods and Results— Tissue discontinuities were simulated in cultures of neonatal rat heart cells grown in 8-armed star patterns. Premature stimulation was applied at the extremity of 1 arm (n=12) while extracellular electrograms were recorded at 24 sites throughout the star. Action potentials were recorded at the following 3 sites: in the stimulated arm and at the discontinuity both proximal to and distal from the star center. Extracellular recordings revealed progressive increases in activation delay (indicative for abnormal CV restitution) only at the discontinuity from arms proximal to the star center. The mean increase in delay was 0.81±0.41 ms/10 ms for recording sites proximal to and 3.13±0.58 ms/10 ms for sites distal from this discontinuity. Depolarizing currents were determined in single cells during premature stimulation and for voltage configurations similar to those arising at the discontinuity. Both voltage-clamp measurements and computer simulations showed that delay at the discontinuity was associated with biphasic, prolonged activation and delayed inactivation of depolarizing current.

Conclusions— Tissue discontinuities cause abnormal CV restitution. Rapid increase in activation after an initial slow activation and delayed inactivation at the discontinuity lengthen the duration of depolarizing current and cause the abnormal restitution.

Key Words: action potentials • conduction • cells • electrophysiology

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