In vivo 2D mapping of impaired murine cardiac energetics in NO-induced heart failure

P-31 MRS studies in humans have shown that an impairment of cardiac energetics is characteristic of heart failure. Although numerous transgenic mouse models with a heart-failure phenotype have been generated, current methods to analyze murine high-energy phosphates (HEPs) in vivo are hampered by limited spatial resolution. Using acquisition-weighted 2D P-31 chemical shift imaging (CSI) at 9.4 Tesla, we were able to acquire P-31 MR spectra over the entire thorax of the mouse with high spatial resolution in defined regions of the heart (the anterior, lateral, posterior, and septal walls) within a reasonable acquisition time of about 75 min. Analysis of a transgenic cardiomyopathy model (double mutant: cardiospecific inducible nitric oxide synthase (iNOS) overexpression and lack of myoglobin (tg-iNOS(+)/myo(-/-)) revealed that cardiac dysfunction in the mutant was associated with an impaired energy state (phosphocreatine (PCr)/adenosine triphosphate (ATP) 1.54 +/- 0.18) over the entire left ventricle (LV; wild-type (WT): PCr/ATP 2.06 +/- 0.22, N = 5, P < 0.05), indicating that in the absence of efficient cytosolic NO scavenging, iNOS-derived NO critically interferes with the respiratory chain. In vivo data were validated against 31p MR spectra of perchloric acid extracts (PCr/ATP: 1.87 +/- 0.21 (WT), 1.39 +/- 0.17 (tg-iNOS(+)/myo(-/-), N = 5, P < 0.05). Future applications will substantially benefit studies on the cause-and-effect relationship between cardiac energetics and function in other genetically well-defined models of heart failure.