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Dissertation
Exercise training protects myocardial mitochondria against ischemia reperfusion-induced injury
ProQuest
Doctor of Philosophy (PHD), University of Florida
2008
Abstract
Coronary artery disease (CAD) is a major contributor to morbidity and mortality. The primary pathological manifestation of CAD is myocardial injury due to ischemia-reperfusion (IR). Given the worldwide prevalence of CAD and the associated IR-induced cardiac injury, understanding the mechanisms of myocardial IR injury as well as developing countermeasures to provide cardioprotection against IR-induced damage is important. In this regard, regular bouts of endurance exercise training (ExTr) protect the heart against IR-induced injury. However, it is unclear whether ExTr-induced cardioprotection against IR injury is mediated through mitochondrial adaptations. These experiments tested the hypothesis that exercise training protects cardiac mitochondria against IR-induced injury. To test this hypothesis, hearts were isolated from exercise-trained and sedentary control animals. Subsequently, hearts were exposed to either IR or continuous perfusion using an in vitro isolated working heart system, and cardiac contractile profiles were measured. At the end of IR or continuous perfusion, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated from the hearts to assess mitochondrial respiratory function and ROS generation. Our results reveal that ExTr protects the heart against IR injury as shown by higher levels of contractile performance during recovery from an IR insult. Moreover, ExTr protects mitochondria, reflected in a higher respiratory control ratio in both SSM and IFM. Additionally, ExTr prevents IR-induced elevation of mitochondrial ROS production and the release of proapoptotic proteins (i.e., cytochrome c and AIF) during an IR insult. Moreover, ExTr increases mitochondrial antioxidant capacity and protects cardiac mitochondria against IR-induced oxidative damage. Collectively, these novel findings reveal that ExTr protects IR-induced mitochondrial injury and provide new insight into the mechanism responsible for exercise-induced cardioprotection.
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Details
- Title
- Exercise training protects myocardial mitochondria against ischemia reperfusion-induced injury
- Resource Type
- Dissertation
- Publisher
- ProQuest
- Number of pages
- 89
- Copyright
- Copyright 2010 by ProQuest LLC. All rights reserved. This edition of the work is protected against unauthorized copying under Title 17, United States Code.
- Identifiers
- 9781124129129; 99380189493806600
- Language
- English
- Awarding Institution
- University of Florida; Doctor of Philosophy (PHD)
- Theses and Dissertations
- Doctor of Philosophy (PHD), University of Florida