THE EFFECT OF AMP DEAMINASE 3 DEFICIENCY ON POST-MYOCARDIAL INFARCT FUNCTIONAL AND HISTOLOGICAL OUTCOMES IN MICE

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Marie Clunan (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: PURPOSE: Humans deficient in the metabolic enzyme AMP deaminase 3 have improved survival and clinical outcomes in cases of revascularization , myocardial infarction , and/or heart failure. Because of the nature of this problem , no clinical trials have been performed to date to control for any confounding variables or conduct in depth analysis on myocardial tissue. The purpose of this study was to use a mouse model to understand the effects of AMP deaminase 3 (AMPD3) deficiency on cardiac functionality after left anterior descending (LAD) artery ligation to simulate myocardial infarction. Furthermore , this study examined how AMP deaminase 3 deficiency impacted infarct size as well as molecular remodeling post-infarct. METHODS: LAD ligation surgery was performed on adult male and female , both knockout (AMPD3 -/-) and wildtype (AMPD3 +/+) mice. Hearts were collected four days and four-weeks post-occlusion and then echocardiogram (n=55) , interstitial fibrosis (n=27) , and morphometric (n=27) analyses performed. Two (genotype) by two (sex) ANOVA's were run to determine statistical significance. The four-day and four-week post-occlusion time points were not compared directly. RESULTS: At four-days post-occlusion no significant differences were detected in echocardiograms , histology , or fibrosis measures. At four-weeks post-occlusion , AMPD3 knockout mice had higher heart rates (p= 0.0068) , and a lower percentage of interstitial fibrosis compared to wildtype mice (p=0.0020). CONCLUSIONS: AMPD3 knockout mice suffer less damage at the cellular level due to infarction compared to wildtype mice. However , further research is warranted on a greater number of subjects to determine the effect AMPD3 has on cardiac functionality and ventricular remodeling.

Additional Information

Publication

Thesis

Language: English

Date: 2019

Keywords

AMP Deaminase, Infarct, Histology, Fibrosis, Echocardiogram, Mice

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