(Circulation. 1999;99:1385-1394.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
From the Departments of Medicine and Biomedical Engineering and the Cardiac Bioelectricity Research and Training Center, Case Western Reserve University, and the Veterans Affairs Medical Center, Cleveland, Ohio.
Correspondence to David S. Rosenbaum, MD, Case Western Reserve University, Department of Biomedical Engineering, Wickenden Building, Room 504, Cleveland, OH 44106-7207. E-mail dsr{at}pace.cwru.edu
BackgroundAlthough T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear.
Methods and ResultsT-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209±46 bpm) that was significantly lower (by 57±36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation.
ConclusionsRepolarization alternans at the level of the single cell accounts for T-wave alternans on the surface ECG. Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death.
Key Words: mapping repolarization fibrillation electrical alternans reentry electrocardiogram
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