Derangements of ion transport and/or intracellular concentrations of ions such as sodium and potassium either accompany or are causally involved in the pathology of several cardiac disease states including ischemic heart disease, sudden cardiac death, and congestive heart failure. Recently, nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to the observation of these intracellular ions in intact perfused hearts. New NMR imaging techniques and equipment now enable similar observations to be made in intact animals. Such an approach offers substantial advantages. Unlike conventional microelectrode techniques, NMR is noninvasive, can be used either in vitro or in vivo, can vary in spatial resolution from bulk tissue to single cells, and is sensitive to conditions of ion binding and exchange. The main goal of this research is to measure the sodium and potassium NMR properties of cardiac tissue for the purpose of a) investigating the role of these ions in cardiac electrophysiology and pathophysiology, and b) obtaining information which will facilitate the understanding and clinical usefulness of sodium NMR images. The NMR relaxation times are extremely important, both due to their sensitivity in reflecting intramolecular interactions and due to their role in determining image contrast. One of the specific goals of this research is to measure the intracellular sodium and potassium relaxation times in perfused heart preparations under control, hypoxic, and ischemic conditions. Another goal is to measure the NMR spectra and relaxation times as a function of time within the cardiac cycle. These studies will determine the feasibility of utilizing NMR to identify regions of pathologically depolarized tissue in an in vivo heart in NMR images. In addition, the results of the relaxation time measurements will be used to identify the intracellular signals on the basis of their relaxation times alone, thus eliminating the need for shift reagents for in vivo studies. Local variations in intracellular sodium and potassium will be monitored under control and ischemic conditions, and proton and sodium images of in vivo hearts will be compared on the basis of the spectroscopic results to determine whether or not sodium images may provide an earlier and more precise definition of pathologic regions.
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