Date of Award

Spring 2020

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. Francis Spinale

First Reader

Dr. Lydia Matesic

Second Reader

Dr. Lydia Matesic

Abstract

Hypertension and vascular stiffness are two physiological conditions that strain the left ventricle (LV) and cause it to gain muscle mass. Eventually, the LV is unable to fill correctly and the patient develops Heart Failure with a preserved Ejection Fraction (HFpEF). Clinically, a patient’s left atrium (LA) area is measured as a diagnostic parameter of HFpEF severity. However, this doesn’t offer a prognosis or threshold of LA size necessitating hospitalization because of variation in patient demographics, genetics, and lifestyle which affect rates of HFpEF progression.

Since there are no medications or effective treatment options for HFpEF patients, there is a substantial need for both therapeutics and disease modeling in order to begin treating patients and predicting the development of their disease. This project aims to determine the usefulness of the LA dilation rate in a HFpEF model, hoping that a predictive regression accounting for individuals’ differences is more valuable than a single LA measurement.

To that end, we employed a pre-clinical model with features mimicking HFpEF in mice. Repeat echocardiographs of the LA area were taken prior to a LV pressure overload (LVPO) procedure, as well as 14 and 28 days afterwards. The data reveal that for both genotypes used in the study, a predictive regression can be used to estimate LA size at any subsequent day in a mouse’s trajectory according to a baseline LA measurement. This modeling offers a prognosis for HFpEF development in mice, and holds potential to be translated to humans after specific adjustments are made.

First Page

1

Last Page

32

Rights

© 2020, Laura B Snyder

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