Biomedical Engineering Reference
In-Depth Information
Multiscale Modeling and Imaging of the Failing
Heart: From Mouse to Human
Andrew D. McCulloch
Abstract Multiscale models of the heart have been developed that integrate both
functionally across biomechanical, electrophysiological, and regulatory functions
and structurally across physical scales of organization from molecule to organ
system. Here, we illustrate the development and application of these models to
improving understanding and management of congestive heart failure. The mouse
is a valuable model organism for studying heart failure because of the availability of
genetically engineered strains harboring mutations that lead to heart failure in
animals and humans. We illustrate this with results from a recent multiscale
model of the heart in mice that harbor a mutation in the myosin regulatory light
chain MLC-2v. Experimental studies in these mice at multiple scales including
in vivo MRI allow us to validate multiscale models and identify integrative
mechanisms of heart failure. In humans, image-based patient-specific multiscale
models of ventricular electromechanics in the failing heart are helping improve
our understanding of therapeutic strategies, especially cardiac resynchronization
therapy (CRT) which is cost-effective strategy for improving cardiac pump func-
tion in patient's whose heart failure is complicated by electrical conduction defects.
However, 30-40% of CRT candidates do not respond to CRT. Patient-specific
models have the potential to better discriminate potential CRT responders.
A.D. McCulloch (
*
)
University of California San Diego, La Jolla, CA 92093-0412, USA
e-mail:
amcculloch@ucsd.edu
