The Role of Mitochondria in Cardiac Protection from Ischemic Injury

Project Description Narrative:

Ischemic heart disease remains the leading cause of death and disability in Wisconsin and the United States. This project represents an investigation of a clinically relevant problem because of the large population of patients with coronary artery disease receiving general anesthesia and the morbidity and mortality associated with myocardial ischemia and infarction. Cardioprotection by anesthetic preconditioning may have important implications in the clinical setting. One is cardioprotection against possible ischemia during the perioperative period in patients with coronary artery disease undergoing noncardiac surgery. Another is protection against the myocardial ischemia expected to occur during cardiac surgery or coronary angioplasty. Volatile anesthetics such as isoflurane used in this proposal have been shown to reduce infarct size when applied before or right after occlusion of the blood flow. The effectiveness of protection by isoflurane has also been observed on patients undergoing coronary artery bypass graft surgery.

Further, the research might lead to novel gene therapeutic approaches for patients suffering from ischemic heart disease. Mitochondria play a central role in energy metabolism and ion homeostasis in the heart during ischemia and reperfusion. Ischemia and reperfusion damage mitochondrial structure and function. Subsequently, mitochondrial dysfunction is an important factor and major causative agent in tissue injury during reperfusion. This project will systematically delineate the mechanisms and novel protective strategies by investigating the role of mitochondria in cardioprotective preconditioning.