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1 Medicine/Cardiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States
2 Radiology, The Johns Hopkins University, Baltimore, Maryland, United States
3 Radiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States
4 Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States
5 Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
6 School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
7 Medicine/Cardiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States; Cardiology, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: rweiss{at}jhmi.edu.
In order to study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo MRI/MRS studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After three weeks of TAC, a significant increase in left ventricular (LV) mass (74±4 mg vs 140±26mg, control vs TAC, respectively, P<0.000005), size (EDV: 48±3 uL vs 61±8uL, P<0.005) and contractile dysfunction (EF: 62±4% vs 38±10%, P<0.000005) was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0±0.1 vs 1.3±0.4, P<0.0005) measured by combined magnetic resonance imaging and 31P spectroscopy (MRI/MRS) . After an additional three weeks, LV mass (LV: 140±26 mg vs 167±36 mg, P<0.01) and cavity size (EDV: 61±8 uL vs 76±8 uL, P<0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with ESV and directly with EF at 6 weeks but not at 3 weeks, suggesting a role of sustained energetic abnormalities on evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 weeks strongly correlated with changes in EDV that developed over the ensuing three weeks. These data suggest abnormal energetics due to pressure-overload predict subsequent LV remodeling and dysfunction.
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