Abstract

The ability of nuclear magnetic resonance spectroscopy to monitor adriamycin (ADR)-induced cardiotoxicity will be studied. Initial studies will be performed on the Langendorff perfused rat heart model using 31P NMR to monitor changes in phosphorus metabolism as a result of ADR exposure. 1H NMR techniques will also be employed to evaluate the potential utility of NMR imaging as a diagnostic tool to monitor drug-induced cardiomyopathy. Spectral perturbations will be correlated with changes in heart functions, morphological changes and changes in the biochemistry and metabolism of the heart. To help evaluate the NMR technique as an indicator of chronic toxicity, studies will be performed on animals with surgically implanted coils; in addition, NMR imaging will be used on rats and rabbits without need for the implants. The NMR method(s) will be """"""""calibrated"""""""" using drugs known to be cardiotoxic and then used to assess the predictive ability of the method on previously untested drugs. Chemicals will also be screened using this methodology for their ability to prevent cardiac toxicity. It is hoped that some of the biochemical processes involved in the expression of cardiomyopathy will also be delineated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035079-03
Application #
3348626
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1985-04-01
Project End
1988-11-30
Budget Start
1987-04-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Atalay, M K; Forder, J R; Chacko, V P et al. (1993) Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging. Radiology 189:759-64
Chatham, J C; Forder, J R (1993) A 13C-NMR study of glucose oxidation in the intact functioning rat heart following diabetes-induced cardiomyopathy. J Mol Cell Cardiol 25:1203-13
Chatham, J C; Hutchins, G M; Glickson, J D (1992) Altered glucose metabolism in adriamycin-induced heart failure. Biochim Biophys Acta 1138:1-5
Chatham, J C; Cousins, J P; Glickson, J D (1990) The relationship between cardiac function and metabolism in acute adriamycin-treated perfused rat hearts studied by 31P and 13C NMR spectroscopy. J Mol Cell Cardiol 22:1187-97
Weiss, R G; Chacko, V P; Glickson, J D et al. (1989) Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts. Proc Natl Acad Sci U S A 86:6426-30