DEVELOP OPEN-CHEST 31P MRS MOUSE HEART

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To develop a rapid, robust, and accurate method for assessing myocardial energetics in mice and demonstrate its applicability to mouse models of acquired and genetic heart disease. MATERIALS AND METHODS: We combined surface coil localization (10-mm diameter, tunable between 1H and 31P, using adiabatic half-passage radiofrequency pulses) and surgery (electrocautery removal of anterior chest wall) to create an open-chest method for acquiring in vivo 31P nuclear magnetic resonance (NMR) cardiac spectra from mice at 4.7T within 12 minutes. Normal BALB/c mice, BALB/c with myocardial infarction (MI), cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta knockout (KO) (CR-PPARd(-/-)) and control loxP-flanked Ppard (Ppard(flox/flox)) mice were examined. RESULTS: The mean phosphocreatine (PCr)/adenosine triphosphate (ATP) ratios in control BALB/c mice, BALB/c MI mice, Ppard(flox/flox) mice, and PPAR-delta KO mice were 2.13 +/- 0.09 (N = 11), 1.35 +/- 0.07 (N = 9, P < 0.001 vs. BALB/c control), 1.92 +/- 0.09 (N = 5), and 1.31 +/- 0.12 (N = 5, P < 0.005 vs. Ppard(flox/flox) control), respectively. The significant depression of myocardial PCr/ATP we observed in these genetic/acquired models of heart disease was in accord with previous data from analogous large animal models. No NMR signal contamination from chamber blood or adjacent skeletal muscle was identified.