In vivo 2D mapping of impaired murine cardiac energetics in NO-induced heart failure.
(31)P 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 (31)P chemical shift imaging (CSI) at 9.4 Tesla, we were able to acquire (31)P 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 (31)P 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.
Flögel
Ulrich
U
Institut für Herz und Kreislaufphysiologie, Universitätsklinikum Düsseldorf, Heinrich Heine Universität, Düsseldorf, Germany. floegel@uni-duesseldorf.de
Jacoby
Christoph
C
Gödecke
Axel
A
Schrader
Jürgen
J
D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D006333:Heart Failure / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008297:Male; D051379:Mice; D009211:Myoglobin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010759:Phosphorus Isotopes; D015854:Up-Regulation
D009211:Myoglobin; D010759:Phosphorus Isotopes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse