Download A New Look at Repolarization Abnormalities and Arrhythmias

JACC Vol. 6, No. I
July 1985:161-2
161
Editorial Comment
A New Look at Repolarization
Abnormalities and Arrhythmias*
ALLAN M. GREENSPAN, MD, FACC
Philadelphia. Pennsylvania
Ordered activation of the heart depends on synchronous and
uniform conduction of the depolarizing electrical wave front
and synchronous repolarization and recovery of excitability,
and thereby obviates the development of substrates for the
generation of arrhythmias. Such substrates occur when there
is incomplete or delayed activation of myocardial segments
( 1) or when there is nonuniform repolarization and recovery
of excitability (2). These conditions can lead to 1) the development of mUltiple activation pathways, allowing for
reentry of the activation wave front; 2) the development of
significant voltage gradients between myocardial segments
that generate local extracellular current which can initiate
abnormal automaticity (3); or 3) the alteration of properties
of conduction and refractoriness that will allow perpetuation
of the spread of abnormal activation wave fronts.
Previously, emphasis was placed on the role of slowed
conduction and conduction block in the generation of reentry
as the major mechanism of clinical arrhythmias (4). More
recently, with the demonstration of early and delayed afterdepolarizations that can be induced to generate repetitive
propagated responses, the concept of triggered automaticity
has been cited as a possible important mechanism for clinical
arrhythmias (5), although there has been no clear clinical
evidence.
Focal repolarization abnormalities. The role of focal
repolarization abnormalities in generating clinical arrhythmias has been discussed theoretically, but has not been given
much emphasis, Part of the reason for this is the
concept that abnormalities of repolarization are usually quite
localized and generate potential differences of limited amplitude such that they cannot be propagated to any degree
outside the local area of abnormality. Therefore their impact
in generating arrhythmias would be small.
Furthermore, unlike the depolarization waveform, re*Editorials published in Journal of the American College ofCardio.logy
reflect the views of the authors and do not necessarily represent the vIews
of JACC or the American College of Cardiology.
From the Department of Clinical Electrophysiology. Hahnemann University. Philadelphia. Pennsylvania.
Address for reprints: Allan M. Greenspan. MD. Clinical Electrophy~­
iology Laboratory. Likoff Cardiovascular Institute of Hahne~ann Umversity. 6617 New College Building. Broad and Vine Streets. PhIladelphIa.
Pennsylvania 19102.
© 1985 by the American College of Cardiology
polarization has been shown to propagate in the normal heart
at such slow rates that there is no distinct repolarization
waveform (6). At any time, a local region undergoing repolarization would be surrounded by regions whose repolarization processes were at a slightly greater or lesser degree
of completion than its own, producing a rather gentle voltage
gradient across the myocardium, which would effectively
buffer any local abnormalities of repolarization in the immediate region (7). Thus it is theorized that only gross
repolarization abnormalities could be transmitted beyond
their local region of origin and have a significant impact on
impulse generation or conduction.
The novel findings in the report of Kupersmith and Hoff
in this issue of the Journal (8) include the demonstration
that abnormalities of repolarization can be transmitted rapidly and over a significant distance (5 to 10 mm) between
isolated segments of a Purkinje fiber with differing repolarization activity by either electrotonic interaction or generation of a propagated response. This might indicate that
abnormalities of repolarization are not spatially limited to
immediate areas of damage or metabolic derangement, and
could have effects from a distance.
Other investigators (9) have suggested that electrotonic
interactions between two regions separated by a well coupled but inexcitable segment could form the substrate for
development of a steeper voltage gradient creating sinks and
sources of current. These in tum could generate local circuit
currents resulting in depolarization-induced automaticity as
in the ischemic border zone model. In the present study the
portion of the fiber tightly compressed by the rubber membrane may provide the functional equivalent of such a well
coupled, inexcitable segment, and thus create the necessary
conditions for transmission of the repolarization abnormality.
Incomplete transmission of repolarization abnormality. Another important finding of Kupersmith and Hoff (8)
is the observation that there can be incomplete transmission
of the repolarization abnormality, perhaps dependent on the
amplitude of the voltage gradient and the components of
longitudinal and axial resistance that affect the degree of
coupling between the segments. Thus, a repolarization abnormality characterized by a prolonged plateau and a secondary hump. which in the abnormal segment produces no
regenerative action potential, when transmitted as only the
secondary hump to the normal segment becomes a delayed
afterdepolarization and triggers a closely coupled repetitive
response that can initiate a sustained arrhythmia.
Electrotonic coupling of remote and abnormal segments. The other novel finding in this report (8) is the
demonstration that transmission of repolarization characteristics is a two-way phenomenon with the capability of
transmitting normalizing properties from the normal to the
deranged segment, as well. This has major implications for
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JACC Vol. 6, No. I
GREENSPAN
EDITORIAL COMMENT
antiarrhythmic drug interventions, because it suggests that
for a drug that alters abnormal repolarization to be effective,
it need not be physically at the site of arrhythmia generation,
but can influence that site from remote areas by electrotonic
coupling to the abnormal segments. Thus a drug could suppress arrhythmias occurring in acutely ischemic tissue even
if there were little or no effective blood supply to the arrhythmogenic region.
Clinical implications. Although further work is required to establish the role of repolarization abnormalities
in the generation of clinical arrhythmias, there are two clinical conditions in which the propagation of repolarization
abnormalities has a plausible role: 1) arrhythmias occurring
in the setting of acute metabolic derangements (electrolyte
disturbances and ischemia), and 2) arrhythmias associated
with the long QT syndrome. In both of these situations
surface epicardial and endocardial recordings of bizarre T
waves have been made that are associated with abnormal
repolarization (10, II). In the case of the acutely ischemic
border zone, these deep negative T waves that generally
precede development of ventricular premature complexes
are associated with the occurrence of separate regions of
current sources and sinks due to differences in the state of
repolarization between ischemic and adjacent normal border
zone tissue. In a patient with the long QT syndrome, a
similar bizarre local endocardial slow wave occurring at the
time of the T wave was also recorded and could well reflect
afterdepolarizations generated by the inhomogenous repolarization found in this condition.
Limitations. There are limitations to the present study.
First, the manipulations performed to generate the repoJarization abnormalities are quite unphysiologic and only demonstrate that the repoiarization abnormalities can be transmitted, without investigating the actual physiologic
circumstances under which they could occur. Second, the
study is purely descriptive, without attempting to analyze
July 1985:161-2
the mechanism for transmission of repolarization abnormalities.
Despite these limitations, the findings of this study that
the properties of repolarization, both normal and abnormal,
under specific circumstances are not spatially limited and
can be transmitted over reasonable distances imply that a
new look should be given to the role of abnormal repolarization in the generation of clinically important arrhythmias.
References
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