? The fundamental premise of this research project is that the intracellular sodium concentration ([Na+]i) provides one of the most sensitive measures of cellular viability. In vivo [Na+]i measurements are, therefore, crucial in the determination of cellular viability. We have developed Na-23 Magnetic Resonance (MR) methods that use shift reagents (SR) to distinguish intra- and extracellular Na+ content and measure [Na+]i in both isolated organs and animals. It is unlikely, however, that SR will ever be applicable for use in humans. Na-23 MR SR methods will be used to provide an """"""""in vivo gold standard"""""""" measurement of intra- and extracellular Na+ content of the isolated and intact heart. These will be combined with state of the art H-1 MR relaxography measures of intra and extracellular H20 fractions to yield [Na+]i. Two new Na-23 MR methods for the discrimination and quantification of [Na+]i will be developed. These Na-23 MR methods will exploit the inverse Laplace transform to full advantage. One method will exploit the intrinsic transverse relaxation characteristics of the Na+ resonance; the other will explore use of longitudinal relaxation reagents to aid in Na+ discrimination. The methods will be validated in studies of the isolated perfused heart. The methods will be extended to the intact heart in living animals with the ultimate goal of studies in the human heart. Sodium homeostasis is crucially involved in vital cell functions, such as excitability, excitation- contraction coupling, energy metabolism, pH regulation, as well as cardiac growth and development. Numerous reports indicate that [Na+]i is increased in several cardiac pathologies, which include ischemiaheperfusion injury, hypertrophy, and heart failure. An increase in [Na+]i results in functional consequences, including slowed relaxation, slower recovery from acidosis, as well as, increasing incidence of arrhythmias. Project studies will measure [Na+]i in the hypertrophied and failing myocardium of rats and mice following pressure overload. ? ? ?
