Quantitative evaluation of left ventricular function in a transgenic mouse model of dilated cardiomyopathy with 2-dimensional contrast echocardiography

The study of transgenic mouse models of human cardiovascular disease has been limited by the small size and high heart rate of the mouse heart. Advances in digital echocardiographic imaging equipment have provided the high spatial and temporal resolution necessary for 2-dimensional (2D) in vivo imaging of the mouse heart. The goal of this study was to test the use of contrast-enhanced 2D echocardiography to quantitatively assess left ventricular (LV) size and function in normal and transgenic mice with dilated cardiomyopathy. Images were obtained with a 12-MHz broadband transducer in the parasternal short-axis view in 8 control mice and 8 transgenic mice with dilated cardiomyopathy resulting from expression of a dominant-negative CREB transcription factor in the heart. LV opacification was achieved with injections of human albumin microspheres, injectable suspension (Optison) (15 to 30 mu L bolus). LV area was measured throughout the cardiac cycle with manual frame-by-frame tracing of the endocardial boundary. End-systolic and end-diastolic areas (ESA and EDA) were measured and fractional area change (FAC) calculated in both groups at baseline and during administration of dobutamine (40 mu g/kg/min intravenously). High-quality 2D images, which yielded LV area over time waveforms, were obtained in all mice. Under baseline conditions, ESA was significantly higher and FAC lower in the transgenic mice compared with their controls. During administration of dobutamine, normal mice had significantly smaller ESA and significantly larger FAC compared with baseline conditions, whereas this trend did not reach significance in the transgenic mice. In summary, quantitative assessment of LV size and function may be achieved with contrast-enhanced 2D echocardiographic imaging. This technique promises to facilitate studies of pathophysiology in murine models of human cardiovascular disease.