Date of Award

6-30-2016

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Francis Spinale

Second Advisor

Tarek Shazly

Abstract

The canonical mechanism of wound healing is disrupted following a myocardial infarction (MI), manifesting as an unregulated response that negatively impacts left ventricular (LV) function. This mechanism, termed post-MI remodeling, culminates in an outcome that favors progression to a systolic heart failure state and death for the patient. Therapeutic approaches following the occurrence of a MI are designed to modulate the natural remodeling process and mitigate the loss of cardiac function. The mechanics and structure of the healing infarct have been the focus of numerous pre-clinical and clinical investigations, leading to the impending clinical introduction of material injections as a means to favorably alter remodeling outcomes. However, to date there is no body of work that provides a coherent framework for evaluation of targeted material therapies. To form a basis for optimization of material-based MI treatments, we have integrated measurements of MI regional mechanics, the morphology of the local extracellular matrix, and the biophysical impact of material injections into the MI region in a porcine model of MI. The combined findings of this study have enhanced a mechanistic understanding of material-based post-MI interventions, elucidated the relationship between MI regional mechanics and LV function throughout the natural and attenuated history of LV remodeling, and has developed mechanical metrics of value to move forth towards future developments of a generalizable computational tools for screening and evaluation of new strategies for MI injections.

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