Vol. 276, Issue 1, H269-H283, January 1999
Cardiac electrical restitution properties and stability of
reentrant spiral waves: a simulation study
Zhilin
Qu,
James N.
Weiss, and
Alan
Garfinkel
Cardiovascular Research Laboratory, Departments of Medicine
(Cardiology), Physiology, and Physiological Science, University of
California, Los Angeles, California 90095
Spiral wave
breakup is a proposed mechanism underlying the transition from
ventricular tachycardia to fibrillation. We examined the importance of
the restitution of action potential duration (APD) and of conduction
velocity (CV) to the stability of spiral wave reentry in a
two-dimensional sheet of simulated cardiac tissue. The Luo-Rudy
ventricular action potential model was modified to eliminate its
restitution properties, which are caused by deactivation or recovery
from inactivation of K+,
Ca2+, and
Na+ currents
(IK,
ICa, and
INa,
respectively). In this model, we find that
1) restitution of
ICa and
INa are the main
determinants of the steepness of APD restitution;
2) for promoting spiral breakup, the
range of diastolic intervals over which the APD restitution slope is
steep is more important than the maximum steepness;
3) CV restitution promotes spiral
wave breakup independently of APD restitution; and
4) "defibrillation" of
multiple spiral wave reentry is most effectively achieved by combining
an antifibrillatory intervention based on altering restitution with an
antitachycardia intervention. These findings suggest a novel paradigm
for developing effective antiarrhythmic drugs.
fibrillation; antiarrhythmic drugs; chemical defibrillation; ventricular tachycardia
