Date of Award
Master of Science in Biomedical Sciences
Qian Chen, PhD
Cathy J. Hatcher, PhD
Bohdan Minczak, MD
Myocardial infarction (MI) is a leading cause of death globally, with over 730,000 cases each year in the United States alone. Factors involved in the prognosis of an MI include identification of the artery occluded, the time to reperfusion, the size of the infarct, and the degree of cardiomyocyte death. Thus, the treatment of MI typically involves targeting one or more of these factors. Timely opening of an occluded artery to reperfuse the ischemic tissue remains the mainstay treatment through either thrombolytic therapy, arterial stenting, or percutaneous coronary intervention. However, reperfusion itself may cause further damage through the generation of reactive oxygen species (ROS) in a process known as myocardial ischemiareperfusion injury. There are no clinically accepted treatments that directly target cardiomyocyte reperfusion injuries, and the pathophysiology of the process remains complex. Due to the high mortality, lack of positive clinical evidence, and complex pathophysiology, it is difficult to safely measure and study MIR injuries in humans. However, parallel animal models that mimic infarctions in an experimental setting will be essential in furthering the understanding and treatment for MIR injuries. In order to progress research in the field of MIR injury, a reliable and reproducible study model must first be established. The goal of the study is to establish two different models of MIR injury and provide positive evidence that they are reproducible, effective, and reliable. The first model will establish an in vivo Left Anterior Descending (LAD) artery ligation model in mice, which will result in an MIR injury observable through ECG changes and through obtaining a percentage of infarction. The second model will establish a Langendorff model that will show similar cardiomyocyte death, measurable through changes to LVESP, LVEDP, dPTd max, dP/dT min, heart rate and coronary flow, and by obtaining a percentage of infarction. We found that, iIn summary, both models showed evidence of MIR injury confirmable through ECG changes, tissue staining, and cardiac function and coronary flow reduction.
Papa, Alexander, "Establishing a Myocardial Ischemia-Reperfusion Injury Model in Mice and Rats using Left Anterior Descending Artery Ligation and Isolated Heart Experiments" (2020). PCOM Biomedical Studies Student Scholarship. 195.