Year: 2012
Type: article
Abstract: 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, postischemic 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 iii 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.iv Dedicated to my little sisters, Heidi and Hannah v Acknowledgements Without guidance and direction from my Advisors, Dr. Mark
Author: Sverre E. Aune
Institution: The Ohio State University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2343201259