Brault, Jeffrey J.Clunan, Marie C.2019-08-222021-08-012019-082019-07-17August 201http://hdl.handle.net/10342/7482PURPOSE: 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.application/pdfenAMP DeaminaseInfarctHistologyFibrosisEchocardiogramMiceHeart--Metabolism--DisordersMyocardial infarctionMaster's Thesis2019-08-19