© 2000 American Heart Association, Inc.
Integrative Physiology |
Role of Structural Barriers in the Mechanism of Alternans-Induced Reentry
From the Heart and Vascular Research Center and Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio.
Correspondence to David S. Rosenbaum, MD, Director, Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Hamman 322, Cleveland, OH 44109-1998. E-mail drosenbaum{at}metrohealth.org
Abstract—Previously,
using an animal model of T-wave alternans in structurally normal
myocardium, we demonstrated that repolarization can alternate with
opposite phase between neighboring myocytes (ie, discordant alternans),
causing spatial dispersions of repolarization that form the substrate
for functional block and reentrant ventricular fibrillation (VF).
However, the mechanisms responsible for cellular discordant alternans
and its electrocardiographic manifestation (ie, T-wave alternans) in
patients with structural heart disease are unknown. We hypothesize that
electrotonic uncoupling between neighboring regions of cells by a
structural barrier (SB) is a mechanism for discordant alternans. Using
voltage-sensitive dyes, ventricular action potentials were recorded
from 26 Langendorff-perfused guinea pig hearts in the absence (ie,
control) and presence of an insulating SB produced by an epicardial
laser lesion. Quantitative analysis of magnitude and phase of cellular
alternans revealed that in controls, action potential duration
alternated in phase at all ventricular sites above a critical heart
rate (269±17 bpm), ie, concordant alternans. Also, above a faster
critical heart rate threshold (335±24 bpm), action potential duration
alternated with opposite phase between sites, ie, discordant alternans.
In contrast, only discordant but not concordant alternans was observed
in 80% of hearts with the SB, and discordant alternans always occurred
at a significantly slower heart rate (by 68±28 bpm) compared with
controls. Therefore, the SB had a major effect on the alternans–heart
rate relation, which served to facilitate the development of discordant
alternans. Whether a SB was present or not, discordant alternans
produced considerable increases (by 
170%) in the maximum spatial
gradient of repolarization, which in turn formed the substrate for
unidirectional block and reentry. However, by providing a structural
anchor for stable reentry, discordant alternans in the presence of a SB
led most often to sustained monomorphic ventricular tachycardia rather
than to VF, whereas in the absence of a SB discordant alternans caused
VF. SBs facilitate development of discordant alternans between cells
with different ionic properties by electrotonically uncoupling
neighboring regions of myocardium. This may explain why
arrhythmia-prone patients with structural heart disease exhibit T-wave
alternans at lower heart rates. These data also suggest a singular
mechanism by which T-wave alternans forms a substrate for initiation of
both VF and sustained monomorphic ventricular
tachycardia.
Key Words: repolarization • reentry • alternans
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