Dobutamine-stress magnetic resonance microimaging in mice - Acute changes of cardiac geometry and function in normal and failing murine hearts

The aim of this study was to assess the capability of MRI to characterize s ystolic and diastolic function in normal and chronically failing mouse hear ts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administrat ion of 1.5 mug/g IP dobutamine. There was a significant increase of heart r ate, cardiac output, and ejection fraction and significant decrease of end- diastolic and end-systolic left ventricular (LV) volumes (P<0.01 each) in n ormal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatatio n. There was a significant decrease of LV ejection fraction in infarcted mi ce (29%) versus sham mice (58%). Mice with MI showed a significantly reduce d maximum LV ejection rate (P<0.001) and LV filling rate (P<0.01) and no in crease of LV dynamics during dobutamine action, indicating loss of contract ile and relaxation reserve. In 4-month-old transgenic mice with cardiospeci fic overexpression of the <beta>(1)-adrenergic receptor, which at this earl y stage do not show abnormalities of resting cardiac function, LV filling r ate failed to increase after dobutamine stress (transgenic, 0.19+/-0.03 muL /ms; wild type, 0.36+/-0.01 muL/ms; P<0.01). Thus, MRI unmasked diastolic d ysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasi ve assessment of systolic and diastolic components of heart failure. This s tudy shows that MRI can demonstrate loss of inotropic and lusitropic respon se in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.