The long-term objectives of my PSA application are two-fold; one, to provide training in the theory and practice of in vivo NMR spectroscopy and two, to further our understanding of myocardial energy metabolism using in vivo NMR spectroscopy. Phase I of this award will allow me the time and support to study the theory of NMR spectroscopy via classes in biochemistry and chemistry and via several inter-departmental myocardial metabolism and in vivo NMR spectroscopy conferences. Doing so I will fulfill the specific aim of the educational aspect of this award which is to expand my knowledge of and increase my experience with in vivo NMR spectroscopy sufficiently such I will be able to design and carry out my own experiments. Part of Phase I and all of Phase II will be dedicated to specific experiments designed to answer questions about heart energy metabolism in starved and diabetic animals. Using 13C and 1H NMR spectroscopic techniques we will develop and validate methods to measure in vivo in rat heart the following rates; glycogen synthesis, steady-state glycogen turnover, glycogen breakdown, and glycolytic flux. This will be done by infusing rats with 13C labelled substrates and following sequential NMR spectra using several different pulse and editing techniques under a variety of physiological conditions. The rates will be quantitated by measuring the enrichment of the 13C compounds in blood as well as measuring them in the same hearts that are freeze-clamped at the end of each experiment. Measurements of, the activities of glycogen phosphorylase and synthase as well as the concentrations of the metabolites and effectors (ATP, glucose-1-phosphate, glucose-6-phosphate, UDP-glucose, lactate, and others) that are critical to control of heart energy metabolism, will complement the in vivo data. The importance of these experiments lies in the facts the heart disease continues to be the leading killer of Americans. Those people with diabetes are at an even greater risk. These techniques allow for the monitoring of heart energetics in real time under a variety of conditions. A more detailed understanding of these energetics could allow development of metabolic therapies directed at improving cardiac function in those with chronic impairments and saving threatened myocardium in those with acute problems. In vivo NMR spectroscopy may be able to be as a non-invasive method of assessing human myocardial metabolism in the future.
| David, M; Petit, W A; Laughlin, M R et al. (1990) Simultaneous synthesis and degradation of rat liver glycogen. An in vivo nuclear magnetic resonance spectroscopic study. J Clin Invest 86:612-7 |
