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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Montesinos, M C; Yap, J S; Desai, A et al. (2000) Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine: evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant Arthritis Rheum 43:656-63
Cronstein, B N; Montesinos, M C; Weissmann, G (1999) Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFkappaB. Proc Natl Acad Sci U S A 96:6377-81
Morabito, L; Montesinos, M C; Schreibman, D M et al. (1998) Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5'-nucleotidase-mediated conversion of adenine nucleotides. J Clin Invest 101:295-300
Zhu, B Q; Sievers, R E; Sun, Y P et al. (1994) Is the reduction of myocardial infarct size by dietary fish oil the result of altered platelet function? Am Heart J 127:744-55
Levitt, M A; Sievers, R E; Wolfe, C L (1994) Reduction of infarct size during myocardial ischemia and reperfusion by lazaroid U-74500A, a nonglucocorticoid 21-aminosteroid. J Cardiovasc Pharmacol 23:136-40
Wolfe, C L; Sievers, R E; Visseren, F L et al. (1993) Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment. Circulation 87:881-92
Wolfe, C L; O'Connell, J W; Sievers, R E et al. (1993) Assessment of perfused left ventricular mass in normal, ischemic, and reperfused myocardium by means of single-photon emission computed tomography of technetium-99m isonitrile. Am Heart J 126:1275-86
Cronstein, B N (1993) The pharmacology of antiinflammatory agents: a new paradigm. Mt Sinai J Med 60:209-17
Vexler, V S; Berthezene, Y; Wolfe, C L et al. (1992) Magnetic resonance imaging demonstration of pharmacologic-induced myocardial vasodilatation using a macromolecular gadolinium contrast agent. Invest Radiol 27:935-41
Le, S P; Chatterjee, K; Wolfe, C L (1992) Adult respiratory distress syndrome following thrombolytic therapy with APSAC for acute myocardial infarction. Am Heart J 123:1368-9

Showing the most recent 10 out of 19 publications