McCallum Basic Health Science Building
Lab Research Focus: NMR Studies of Intact Hearts
My laboratory investigates biochemical processes in the beating rat heart using phosphorus and sodium NMR spectroscopy. The heart is essentially a pump made of powerful muscle tissue which burns metabolites, particularly fatty acids, producing phosphocreatine and ATP. The latter are utilized to fuel precisely timed cycles of contraction followed by relaxation in the cells of the heart muscle, thus developing and relaxing the force which creates the pumping action. One of the modern techniques that enables the biochemical investigation of complex, integrated systems such as heart muscle is Nuclear Magnetic Resonance spectroscopy (NMR). In simple terms, NMR consists of recording signals broadcast by individual atoms in the sample under investigation. Analysis of spectra provides information about the types and concentrations of various metabolites. When spectra are obtained as a function of time and some experimental perturbation is imposed on the system, valuable kinetic and other information can be collected. NMR allows analysis of intact organs. For instance, a beating rat heart develops force and pumps fluids while levels of ATP, phosphocreatine and other metabolites are monitored.
We have been carrying out studies of the heart by shift-reagent-aided Na-NMR spectroscopy. This technique allows us to investigate the interrelations of pacing, force development, cellular energy stores, intracellular pH and intracellular sodium levels in the perfused, beating heart under normal or perturbed (hypoxia, ischemia, acid loading) physiological conditions.
We use NMR to monitor the changing levels of high-energy phosphate compounds, intracellular pH, and intracellular sodium ions in perfused hearts subjected to experimental protocols which mimic the physiologic state of the diseased heart. Throughout the experiment, the intact heart maintains its function so we can obtain simultaneous information on the effect of a particular protocol on both metabolite levels and the overall physiologic function, thus gaining essentially in vivo biochemical information.
The sodium concentration gradient, maintained by the Na/K ATPase pump, is a crucial component in the coupling of the electric events that control the rhythm of the heart to the contractile mechanism. Consequently, our goal has been the investigation of this coupling and its correlation to high-energy phosphate metabolism.
Studies continue on the correlation among the rate of heart beats, sodium levels, bioenergetics and the pumping force developed by the heart, and on the details of the mechanisms through which oxygen deprivation affects heart function.
Gabriel A. Elgavish (b. 1942) received his B.S. degree in Chemistry from the Hebrew University of Jerusalem (1967), and his M.S. degree from Tel-Aviv University (1972). He did graduate studies in NMR spectroscopy at the Weizmann Institute of Science in Rehovot, Israel (Ph.D. 1978). His interest in biological systems continued during two years of postdoctoral studies at the NIH. A Professor of Biochemistry and Molecular Genetics, Dr. Elgavish joined the UAB faculty in 1981. His research is currently funded by NIH and the pharmaceutical industry.