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The Role of Reactive Oxygen Species in Post-Ischemic Low Flow in the Myocardium

Aune, Sverre Erik

Abstract Details

2012, Doctor of Philosophy, Ohio State University, Biophysics.
Reperfusion of the ischemic myocardium occurs in nearly 2 million people annually in the United States as a complication of cardiovascular disease, in patients experiencing cardiac arrest, myocardial infarction or undergoing cardioplegic arrest during cardiac surgery. Various levels of low flow are induced by such ischemic events, most notably in the moments following ischemia. However, the post-ischemic low flow period has hardly been examined in the literature. The work presented in this dissertation explores the role of reactive oxygen species (ROS) generation in global ischemia, post-ischemic low flow, and subsequent full reperfusion of the myocardium. This dissertation consists of three parts. In Chapter 2, an isolated buffer-perfused rat heart model was employed to explore both low pressure and low coronary flow as interventions in global cardiac ischemia. The ROS burst was observed upon full reperfusion in rat hearts, with differences in ROS generation between the cellular and vascular compartments. Differences in recovery of left ventricular (LV) function were also observed, with LV functional preservation at 10% low flow, but not at 0.5% low flow intervention. In Chapter 3, a novel model of the isolated heart is described, in which whole blood is recirculated throughout experimentation. Blood-perfused and buffer-perfused hearts were noted to respond similarly to global ischemia and low flow intervention. Also, a method describing detection of the ROS burst at reperfusion in blood-perfused hearts is described. A characteristic acute, short-lived formation of hydrogen peroxide was discovered in blood-perfused hearts subjected to ischemia and reperfusion. In Chapter 4, the neutrophil elastase inhibitor Sivelestat is examined for putative cardioprotective properties. Sivelestat was noted to possess dramatic infarct-sparing properties in the isolated heart, along with the ability to preserve LV function. ROS production was examined, and Sivelestat was shown to reduce ROS in ischemic-reperfused hearts and also in hypoxic-reoxygenated aortic endothelial cells. The aim of Chapter 4 is to introduce Sivelestat to the heavily investigated field of cardiac pharmacology.
Mark Angelos, M.D. (Committee Chair)
Periannan Kuppusamy, Ph.D. (Committee Member)
Valery Khramtsov, Ph.D. (Committee Member)
Jonathan Davis, Ph.D. (Committee Member)
Michael Bisesi, Ph.D. (Committee Member)
135 p.

Recommended Citations

Citations

  • Aune, S. E. (2012). The Role of Reactive Oxygen Species in Post-Ischemic Low Flow in the Myocardium [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338233129

    APA Style (7th edition)

  • Aune, Sverre. The Role of Reactive Oxygen Species in Post-Ischemic Low Flow in the Myocardium. 2012. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1338233129.

    MLA Style (8th edition)

  • Aune, Sverre. "The Role of Reactive Oxygen Species in Post-Ischemic Low Flow in the Myocardium." Doctoral dissertation, Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338233129

    Chicago Manual of Style (17th edition)