The role of cardiac mitochondria in myocardial ischemia/reperfusion injury
Frasier, Chad R.
Cardiovascular disease (CVD) exerts economic and humanitarian costs that are unparalleled by any other disease. Of the many etiologies of CVD, myocardial infarction accounts for over 50% of the associated mortality and anything that can decrease the extent of infarction could drastically impact the burden of CVD. The purpose of this work was to further our understanding of the role of cardiac mitochondria in ischemia/reperfusion injury. Herein I found that physiologic (exercise) and pharmacologic (Bendavia) interventions that lessen the oxidative burden during ischemia/reperfusion have the potential to limit myocardial infarction. Under conditions of oxidative stress, animals who received short term exercise (Ex) were better able to maintain the glutathione couple in a reduced state, likely through an increase in glutathione reductase (GR) activity. This phenotypic change was associated with decreased reactive oxygen species (ROS) accumulation and a lower incidence of fatal ventricular arrhythmias. Furthermore, I found that ROS generated within the cytosol, and not the mitochondria, during bouts of Ex are important signaling molecules that increase GR activity and this increased activity may be responsible for the cardioprotective effects observed with Ex. Finally, I found that treatment with the mitochondrially-targeted peptide Bendavia was successful at lowering infarct size in isolated guinea pig hearts, due to an ability to decrease ROS accumulation and maintain mitochondrial energetics. Taken together, these studies suggest that therapies aimed at decreasing mitochondrial ROS and/or maintaining mitochondrial energetics during ischemia/reperfusion may have significant clinical impact.
Frasier, Chad R.. (January 2012). The role of cardiac mitochondria in myocardial ischemia/reperfusion injury (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/3886.)
Frasier, Chad R.. The role of cardiac mitochondria in myocardial ischemia/reperfusion injury. Doctoral Dissertation. East Carolina University, January 2012. The Scholarship. http://hdl.handle.net/10342/3886. February 21, 2019.
Frasier, Chad R., “The role of cardiac mitochondria in myocardial ischemia/reperfusion injury” (Doctoral Dissertation., East Carolina University, January 2012).
Frasier, Chad R.. The role of cardiac mitochondria in myocardial ischemia/reperfusion injury [Doctoral Dissertation]. Greenville, NC: East Carolina University; January 2012.
East Carolina University