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
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Recommended Citation
Disser, Jenna Rose, "AUTONOMIC MODULATION OF CARDIAC FUNCTION IN HYPERTROPHIC CARDIOMYOPATHY", Open Access Master's Thesis, Michigan Technological University, 2024.
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Cardiology Commons, Cardiovascular Diseases Commons, Disease Modeling Commons, Medical Neurobiology Commons, Nervous System Diseases Commons, Neurology Commons, Neurosciences Commons, Other Neuroscience and Neurobiology Commons, Pathological Conditions, Signs and Symptoms Commons, Physiological Processes Commons