Author ORCID Identifier
Date Available
8-2-2021
Year of Publication
2021
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Engineering
Department/School/Program
Mechanical Engineering
First Advisor
Dr. Jonathan F. Wenk
Abstract
Greater than one in three American adults have at least one type of cardiovascular disease, a major cause of morbidity. Computational cardiac mechanics has become an important part of the research effort to understand the heart’s response to mechanical stimuli and as an extension, disease progression and potential therapies. To this end, the present work aims to extend these efforts by implementing a cell level contractile model in which active stress generation in muscle tissue is driven by half-sarcomere mechanics. This is accomplished by enhancing the MyoSim model of actin and myosin in order to produce a multiscale model. This contraction model simulates cross-bridge dynamics and captures key components of contraction such as length-dependent activation, Ca2+ activation and sensitivity, and filament cooperativity. Embedding this physiologically motivated contraction model allows for the testing of hypotheses and predictions regarding the interplay between molecular mechanisms and organ level function, while capturing spatial heterogeneity. This multiscale approach has been used to predict an increase in the end-systolic pressure-volume relationship due to the inclusion of a recently discovered super-relaxed state in left-ventricle simulations. It has also been used to predict a decrease in stress generation and efficiency in skeletal muscles due to myofibril misalignment. Finally, the foundation for cardiac growth and remodeling simulations has been implemented.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2021.321
Funding Information
This work was supported by the following:
- Halcomb Fellowship in Medicine and Engineering (2019 - 2021)
- National Institutes of Health (UO1HL133359 and S10RR029541) (2016 - 2021)
Recommended Citation
Mann, Charles Kurtis, "Multiscale Finite Element Modeling of Active Contraction in Striated Muscle" (2021). Theses and Dissertations--Mechanical Engineering. 177.
https://uknowledge.uky.edu/me_etds/177
