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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. January 20, 1986 TO: DR. S. C. SOMMERS AND STAFF FROM: D. H. Ford 0)s,6A-0V W4 v P ~ RE: Site visit with Dr. Mary Osbakken, University of Pennsylvania, January 14, 1986. Grant Application entitled, 1131P NMR Study of Cardiac Metabolism in Health and Disease." GOAL To evaluate the effects of ventricular volume overload hypertrophy in dogs on the high energy phosphate metabolism of the myocardium by utilizing 31P NMR• She plans to relate work load to phosphorylation potential. This first study is designed to study left heart failure, but she plans to undertake a parallel study at a later date on right heart failure. Thus, the study relates mechanical work performed in a failing heart with the cardiac muscle metabolism. REVIEW In her discussion of the problem of applying NMR to whole animal studies, Dr. Osbakken described the numerous approaches she has attempted and their apparent reasons for failure, before developing her current procedure in which the NMR coil is placed through a thoracic window over the heart. She will be able to correlate heart function in relation to energy metabolism in controls and in animals with left heart failure due to overload. How much overload in- duces how much metabolic distortion? Evaluations of mechanical work performed will also be obtained. Further, she will attempt to revert hearts in an un- stable state to a normal state by pharmacological manipulation with chronotropic drugs such as digitalis. Since Dr. Osbakken is a trained clinical cardiologist, .she views these investigations as precursors for the use of 31P NMR techniques to delineate clinical problems. Conceivably, a measure of the degree of altered cardiac energy metabolism could be correlated to the degree of failure. COMMENT Dr. Osbakken is a bright, enthusiastic young investigator with what appears to be a good background in clinical cardiology. From her clinical experience, she has perceived areas in cardiac physiology and metabolism which need further definition in order to better treat the cardiac patient. She believes that the dog model which she has developed, utilizing NMR techniques, will provide answers in these areas. She has already accumulated some preliminary data which suggest that the technique is applicable for this purpose. Thus, the study is relevant in relation to determining what is happening to cardiac energy metabolism during left ventricular failure and would appear important to the goals of CTR. Donald Ford DF/s