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

The study of transgenic mouse models of human cardiovascular disease has be en limited by the small size and high heart rate of the mouse heart. Advanc es in digital echocardiographic imaging equipment have provided the high sp atial and temporal resolution necessary for 2-dimensional (2D) in vivo imag ing of the mouse heart. The goal of this study was to test the use of contr ast-enhanced 2D echocardiography to quantitatively assess left ventricular (LV) size and function in normal and transgenic mice with dilated cardiomyo pathy. Images were obtained with a 12-MHz broadband transducer in the paras ternal short-axis view in 8 control mice and 8 transgenic mice with dilated cardiomyopathy resulting from expression of a dominant-negative CREB trans cription factor in the heart. LV opacification was achieved with injections of human albumin microspheres, injectable suspension (Optison) (15 to 30 m u L bolus). LV area was measured throughout the cardiac cycle with manual f rame-by-frame tracing of the endocardial boundary. End-systolic and end-dia stolic areas (ESA and EDA) were measured and fractional area change (FAC) c alculated in both groups at baseline and during administration of dobutamin e (40 mu g/kg/min intravenously). High-quality 2D images, which yielded LV area over time waveforms, were obtained in all mice. Under baseline conditi ons, ESA was significantly higher and FAC lower in the transgenic mice comp ared with their controls. During administration of dobutamine, normal mice had significantly smaller ESA and significantly larger FAC compared with ba seline conditions, whereas this trend did not reach significance in the tra nsgenic mice. In summary, quantitative assessment of LV size and function m ay be achieved with contrast-enhanced 2D echocardiographic imaging. This te chnique promises to facilitate studies of pathophysiology in murine models of human cardiovascular disease.