The most common reason for a patient to visit the emergency department is chest pain caused by myocardial ischemia. Myocardial ischemia develops from inadequate perfusion of myocardial tissue and indicates the presence of surprising range of conditions, including coronary artery disease, coronary microvascular dysfunction, Takotsubo cardiomyopathy, and coronary artery dissection, and other potentially fatal cardiac diseases. If left untreated, the long term effects of these diseases can lead to significant decreases in quality of life and increased mortality. Current noninvasive tests to detect ischemia may be limited by an incomplete understanding of the mechanisms used to induce the stress (exercise or pharmacological agents) or the limited understanding of how ischemic signals change over time. These limitations increase the risk for failed detection of deadly cardiac diseases and explain the unsatisfactory accuracy of current diagnostic and monitoring approaches. The goal of this dissertation was to leverage recent experimental findings and breakthroughs about the onset and progression of ischemia as the basis for a comprehensive re-evaluation of acute myocardial ischemia. First, we refined our experimental model to include comprehensive electrical measurements sampled simultaneously from within the myocardium, on the heart surface, and on the torso surface. We then built on our experience with our novel large-animal experimental models of ischemia to measure and characterize the electrical changes that arise during acute myocardial ischemia created from various types of ischemic stress. We also explored possible mechanistic drivers for these differences. Finally, we assessed the transient changes common to ischemic signatures, including the appearance and disappearance of ischemic potentials as recorded from epicardial and torso surface measurements.
Posted by: Nathan Galli