Computer model of electrophysiologic instability in very small
heterogeneous ventricular syncytia.
Nordin, Charles.
Department of Medicine, Albert Einstein College of Medicine, Bronx,
New York
APStracts 3:0477H, 1996.
Computer simulations based on a model of transmembrane currents and
intracellular Ca2& flux of an isolated guinea pig myocyte (26)
have previously shown that very small heterogeneous ventricular
myocardial syncytia can be constructed in which trains of sustained,
nondriven action potentials are initiated and terminated with
critically timed premature stimulations by a nonreentrant mechanism.
This paper examines in more detail the characteristics of such
syncytia and nature of the responses. When cells with the normal
configuration of equations were connected by high resistance gap
junctions to other cells whose configuration was modified to
reproduce a myocyte with mild Ca2& overload and two regenerative
levels of diastolic potential, critically timed stimulations shifted
the electrical response of the syncytium between a stable phase,
where all myocytes were quiescent until stimulated and generated full
action potentials from resting potentials between -90 and -65 mV, and
an oscillatory phase, where all cells generated sustained trains of
nondriven action potentials from takeoff potentials between -70 and
-30 mV. The following predominant responses were observed in such
syncytia: 1) a range of 40-60 msec starting at the refractory period
with an inverse relationship between prematurity of the stimulation
and time to the first upstroke of nondriven activity, followed by a
much shorter period with a direct relationship; 2) delay shorter than
a full compensatory pause following single premature stimulations
that do not terminate spontaneous action potentials; and 3)
entrainment of nondriven action potentials with short bursts of
stimulations at rates just above the intrinsic rate of spontaneous
activity, and termination at faster rates. The propensity to develop
nondriven action potentials was enhanced by Ca2& loading. Other
simulations demonstrated that activity can propagate in syncytia of
more than 100 myocytes from small foci to generate full action
potentials in larger regions of normal cells. Analysis of the model
shows that these patterns arise primarily from crucial, dynamic
relationships between membrane potential, intracellular Ca2&
cycling, and gap junction currents. The results suggest that highly
localized interactions between normal and depolarized myocytes in
uncoupled heterogeneous syncytia may reproduce many of the
characteristic responses of ventricular tachycardia.
Received 4 March 1996; accepted in final form 1 October 1996.
APS Manuscript Number H211-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996