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(Circulation. 1998;98:2774-2780.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart
Presented in part as the NASPE Young Investigator Award presentation, Seattle, Wash, May 1996.
From the Departments of Medicine and Biomedical Engineering and The Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, Cleveland, Ohio, and The Veterans Affairs Medical Center, Cleveland, Ohio.
Correspondence to Kenneth R. Laurita, PhD, Case Western Reserve University, Department of Biomedical Engineering, Wickenden Bldg, Room 504, Cleveland, OH 44106-7207. E-mail KLR2{at}po.cwru.edu
Background—Previously, we have shown that a premature stimulus can significantly modulate spatial gradients of ventricular repolarization (ie, modulated dispersion), which result from heterogeneous electrophysiological properties between cells. The role modulated dispersion may play in determining electrical instability in the heart is unknown.
Methods and Results—To determine if premature stimulus–induced changes in repolarization are a mechanism that governs susceptibility to cardiac arrhythmias, optical action potentials were recorded simultaneously from 128 ventricular sites (1 cm2) in 8 Langendorff-perfused guinea pig hearts. After baseline pacing (S1), a single premature stimulus (S2) was introduced over a range of S1S2 coupling intervals. Arrhythmia vulnerability after each premature stimulus was determined by measurement of a modified ventricular fibrillation threshold (VFT) during the T wave of each S2 beat (ie, S2-VFT). As the S1S2 interval was shortened to an intermediate value, spatial gradients of repolarization and vulnerability to fibrillation decreased by 51±9% (mean±SEM) and 73±45%, respectively, compared with baseline levels. As the S1S2 interval was further shortened, repolarization gradients increased above baseline levels by 54±30%, which was paralleled by a corresponding increase (37±8%) in vulnerability.
Conclusions—These data demonstrate that modulation of repolarization gradients by a single premature stimulus significantly influences vulnerability to ventricular fibrillation. This may represent a novel mechanism for the formation of arrhythmogenic substrates during premature stimulation of the heart.
Key Words: action potentials • arrhythmia • reentry • mapping • pacing
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