Nitric Oxide and Postconditioning: Cardioprotective Methods for Acute Care of Ischemia Reperfusion Injury

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Nitric Oxide and Postconditioning: Cardioprotective Methods for Acute Care of Ischemia Reperfusion Injury

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dc.contributor.advisor Huang, Paul Lee
dc.contributor.author Pong, Terrence Kwok Cay
dc.date.accessioned 2012-11-13T17:57:05Z
dash.embargo.terms 2013-10-05 en_US
dash.embargo.terms 2013-10-05
dc.date.issued 2012-11-13
dc.date.submitted 2012
dc.identifier.other http://dissertations.umi.com/gsas.harvard:10540 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9888979
dc.description.abstract Timely 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. en_US
dc.description.sponsorship Engineering and Applied Sciences en_US
dc.language.iso en_US en_US
dash.license LAA
dc.subject eNOS en_US
dc.subject biomedical engineering en_US
dc.subject cellular biology en_US
dc.subject biosensors en_US
dc.subject echocardiography en_US
dc.subject myocardial infarction en_US
dc.subject nitric oxide en_US
dc.subject postconditioning en_US
dc.title Nitric Oxide and Postconditioning: Cardioprotective Methods for Acute Care of Ischemia Reperfusion Injury en_US
dc.type Thesis or Dissertation en_US
dc.date.available 2013-10-05T07:30:29Z
thesis.degree.date 2012 en_US
thesis.degree.discipline Engineering Sciences en_US
thesis.degree.grantor Harvard University en_US
thesis.degree.level doctoral en_US
thesis.degree.name Ph.D. en_US
dc.contributor.committeeMember Parker, Kevin en_US
dc.contributor.committeeMember Joshi, Neel en_US

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