Many investigators have sought to discover a biochemical/metabolic basis for heart failure but, to date, no clear relationship has been found. To test the hypothesis that energy production and/or utilization is defective in hypertrophied and failing myocardium, we will use nuclear magnetic resonance spectroscopy to evaluate myocardial metabolism in three animal models of cardiac hypertrophy and failure. The animal models to be studied include 1) the spontaneously hypertensive rat, 2) an aortic constriction rat model, and 3) a bilateral renal arterial stenosis canine model of hypertrophy. The research project will be performed in two phases. Phase one will consist of using phosphorous-31 and carbon-13 spectroscopy to evaluate high energy phosphates, flux through creatine kinase, and glucose and fatty acid metabolism in working perfused hearts obtained from spontaneously hypertensive and aortic constricted rats with various degrees of cardiac hypertrophy and failure. Phase two will consist of using phosphorous-31 spectroscopy to evaluate phosphorous metabolism in vivo in the three animal models of hypertrophy listed above. This will be accomplished in the open-chest preparation using a surface coil to localized the left ventricle, in closed-chest canine model using topical magnetic resonance. The studies on closed-chest preparations using surgically implanted surface coils, and in the closed-chest preparations will be done longitudinally using each animal as its own control. The data will be analyzed with emphasis on correlations between the degree of hypertrophy and hemodynamic dysfunction, and alterations in high energy phosphate metabolism (as assessed by P-31 spectroscopy) and/or alterations in substrate preference (as assessed by C-13 spectroscopy) in hypertrophied and failing hearts.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001972-04
Application #
3082396
Study Section
(SRC)
Project Start
1986-09-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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