Nitric Oxide and Postconditioning: Cardioprotective Methods for Acute Care of Ischemia Reperfusion Injury
Pong, Terrence Kwok Cay
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CitationPong, Terrence Kwok Cay. 2012. Nitric Oxide and Postconditioning: Cardioprotective Methods for Acute Care of Ischemia Reperfusion Injury. Doctoral dissertation, Harvard University.
AbstractTimely coronary artery reperfusion is essential to prevent myocyte death following myocardial infarction. The act of restoring blood flow however, paradoxically reduces the beneficial effects of reperfusion. This phenomenon, termed myocardial reperfusion injury, refers to the injury of cardiac myocytes that were viable immediately before reperfusion. Recent studies have shown that the timing and hemodynamic sequence of events which govern reperfusion can help to minimize the severity of reperfusion injury. The term postconditioning describes a modified form of reperfusion that involves a series of flow interruptions which confer significant cardioprotection to the heart. This thesis investigates ischemic postconditioning and endothelial nitric oxide synthase (eNOS) phosphorylation as cardioprotective therapies against reperfusion injury. In the first half of this thesis, we test the hypothesis that phosphorylation of eNOS serves as a cardioprotection nodal point for ischemic postconditioning. We show that phosphorylation of eNOS increases enzyme activity and that its product, nitric oxide, plays a critical role in cardioprotection. A number of cardiac dysfunctions arise after reperfusion and we address the effects of postconditioning on infarct size and myocardial blood flow. The second half of this thesis introduces the use of magnetic relaxometry sensors to detect cardiac biomarkers. The ability to non-invasively measure infarct size in small animals would be helpful in studying models of myocardial ischemia-reperfusion injury. We investigate the use of implantable biosensors in vivo and show that the cumulative detection of cardiac biomarkers correlates with infarct severity.
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