This application investi-gates a marker of viability in post-ischemic hearts, altered substrate preference. Hearts normally use exogenous long-chain fatty acids (LC-FA) as the preferred substrate for energy production. LC-FA also may be stored as triglycerides (TG) but storage of LC-FA occurs at a low rate in normal hearts. As a result, the TG content of normal hearts is low. Oxidation of alternate substrate, such as glucose also is low in normal hearts. Viable post-ischemic myocardium demonstrates a pattern of substrate preference different from normal hearts. Specifically, oxidation of glucose and storage of LC-FA, a glycolysis-dependent process, are enhanced. These changes increase the content of TG in viable post-ischemic myocardium, an event that has been reported by histological, radionuclide, tomographic and magnetic resonance imaging analyses. Despite the fact that enhanced LC-FA storage is one hallmark of viable post-ischemic myocardium, little is known about the relationship between LC-FA storage and altered substrate preference in post-ischemic myocardium. Also, the underlying cause(s) of altered substrate preference in post-ischemic myocardium is not known. Consequently, the application has two goals. The first goal is to quantitate thoroughly the altered substrate preference in isolated post-ischemic rat hearts using 13C-magnetic resonance spectroscopy and radionuclide technologies. The second goal is to determine the underlying cause(s) for altered substrate preference using enzymatic analyses. Accomplishing these goals will delineate the mechanism and importance of enhanced LC-FA storage as a marker for myocardial viability in post-ischemic hearts.
