Biophysical Models of the Cardiovascular System - Systems Biology: Networks, Models, and Applications - page 279

INTEGRATIVE MODELING OF ELECTRICAL CONDUCTION
IN THE CARDIAC VENTRICLES
Computational models of the cardiac myocyte have contributed greatly
to our understanding of myocyte function. This is in large part due to a
rich interplay between experiment and modeling—an interplay in which
experiments inform modeling, and modeling suggests new experiments.
Studies of cardiac ventricular conduction have to a large extent lacked
this interplay. Stated more precisely, both two- and three-dimensional
models of cardiac tissue as well as three-dimensional structurally
detailed models of the cardiac ventricles have been used to simulate con-
duction in the heart. However, the extent to which these models can
reproduce as well as predict experimental data has seldom been tested.
“Closing the loop” between experimental and modeling studies of
electrical conduction within the ventricles is a necessary step toward
relating molecular and cellular events that are the basis of arrhythmia to
their functional consequences at the level of whole-heart function.
The following sections describe one approach to this problem.
In this approach, we (a) model ventricular geometry and fiber ori-
entation in the same hearts that have been electrically mapped using
data obtained from diffusion tensor magnetic resonance imaging
(DTMRI); (b) construct computational models of the imaged hearts;
and (c) compare simulated conduction properties with those measured
experimentally in the same heart as a quantitative test of the models.
Measuring the Fiber Structure of the Cardiac Ventricles Using DTMRI
In addition to the biophysical properties of cells, the geometry and
spatial orientation of ventricular fibers plays a critical role in shaping
electrical propagation within the ventricles. Conduction is influenced
by properties of tissue geometry [46-48] and is anisotropic, with current
spread being most rapid in the direction of the fiber long axis [49-55].
The spatial rate of change of fiber orientation also governs conduction
properties [56,57]. Remodeling of both ventricular geometry and fiber
organization is a prominent feature of several cardiac pathologies [58-68],
and these alterations may figure importantly in arrhythmogenesis [69].
A detailed knowledge of ventricular geometry and fiber orientation,
how it may be remodeled in cardiac pathology, and the effects of this
remodeling on ventricular conduction is therefore of fundamental
importance to the understanding of cardiac ventricular electromechanics
in health and disease.
Present understanding of ventricular fiber organization is based on
fiber dissections of whole hearts [70-72] and histological measurement
of fiber orientation in transmural plugs of ventricular tissue [73-77].
The principle conclusions of this work are that cardiac fibers are
arranged as counter-wound helices encircling the ventricular cavities,
and that fiber orientation depends on transmural location, with fiber