Date of Award

2024

Document Type

Open Access Master's Thesis

Degree Name

Master of Science in Biological Sciences (MS)

Administrative Home Department

Department of Biological Sciences

Advisor 1

Robert A. Larson

Committee Member 1

Qing-Hui Chen

Committee Member 2

William Cooke

Committee Member 3

Thomas Werner

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. In Chapter 2 we demonstrated abnormal activation of vagal afferent activity in a mouse model of HCM. This dysfunction was also witnessed in our control model. Additionally, we demonstrated that the quantity of LV β1Rs was reduced in the HCM mouse model. Furthermore, we examined cardiac β1R function while eliminating autonomic reflex influence. We demonstrated that HR in response to ramped infusion of dobutamine was similar between HCM and wild-type (WT) mice whereas increases in dP/dt max was attenuated in HCM mice. We speculate that the differential inotropic and chronotropic responses to dobutamine could be due to regional differences in β1R expression or contractile dysfunction in HCM mice.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Saturday, March 01, 2025

Share

COinS