Author ORCID Identifier

Defense Date


Document Type


Degree Name

Master of Science


Physiology and Biophysics

First Advisor

Stefano Toldo

Second Advisor

Fadi Salloum

Third Advisor

Roland Pittman


Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial damage during an AMI directly correlates to a poorer prognosis for the development of HF, reperfusion injury is a phenomenon that must be addressed for patients to have better outcomes. An inflammatory response to the myocardium is one of the components that promote myocardial damage during Ischemia/Reperfusion (I/R). Interleukin-18 is a pro-inflammatory cytokine that is elevated in the setting of acute myocardial infarction and promotes recruitment and activation of leukocytes, further upregulating the inflammatory response. Considering literature showing T-lymphocytes are involved and augmented in I/R, we hypothesize that IL-18 mediated activation of T-lymphocytes polarizes them to induce myocardial damage.

By utilizing the IL-18KO mouse model, we were able to show in this study that the absence of endogenous IL-18 significantly reduced infarct size. Characterization of the differences in infiltrating leukocyte populations into the myocardium 24 hours after I/R between WT and IL-18KO showed that while IL-18KO mice display a similar percentage of infiltrating leukocytes as WT mice, they have significantly reduced populations of T-lymphocytes. IL-18KO mice had a smaller percentage of infiltrating CD4+, especially Th1 cells, and CD8+ T-cells following I/R. Further, conducting an adoptive transfer study utilizing the IL-18R KO mouse model, we were able to show that restoration of the IL-18 signaling pathway in leukocytes increased infarct size. The finding of this pilot experiment suggests that IL-18 signaling in leukocytes is a central process during inflammation that contributes to myocardial damage and increased infarct size. The results from this study pave the future direction of specifying which leukocyte populations contribute to reperfusion injury in an IL-18 dependent mechanism.


© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission


Available for download on Sunday, July 20, 2025