TRANSTHORACIC ECHOCARDIOGRAPHY IN MODELS OF CARDIAC DISEASE IN THE MOUSE

Background Transthoracic echocardiography (M-mode and Doppler) offers a noninvasive approach for in vivo evaluation of the mouse heart. The present study examines its usefulness for assessing the morphological/ functional phenotype of the left ventricle (LV) in several transgenic and surgical murine models of cardiac disease. Methods and Results Obs ervations were made in 83 intact, anesthetized mice. In mice with a su rgical arteriovenous fistula, volume overload and LV dilation were det ected. In normal mice, echocardiographic indexes of increased contract ility (dobutamine) were confirmed by LV dP/dt(max). In transgenic mice with overexpression of the beta(2)-adrenergic receptor, heart rate an d mean velocity of circumferential fiber shortening were increased, in dicating enhanced contractility. In colony screening of transgenic mic e overexpressing the H-ms gene, 45% had increased LV wall thickness (> 0.9 mm), and those showing a striking increase were selected for breed ing. In mice with LV hypertrophy (aortic constriction) and normal mice , the actual LV mass determined by echocardiography correlated well (r =.93), and 95% confidence limits were determined. The maximum intraobs erver and interobserver coefficients of variation for M-mode data were 0.03+/-0.29 mm (+/-2 SD), <10% for LV internal dimensions but 27% to 30% for wall thickness. Conclusions These studies provide the first ap plication of transthoracic echocardiography for morphological/function al characterization of the cardiac phenotype in transgenic and surgica l murine models, including (1) high reliability for detecting LV chamb er dilation and function; (2) reliability (and its limits) for determi ning abnormal LV wall thickness and LV mass; (3) identification of mar ked, sometimes asymmetrical, hypertrophy in a transgenic model of hype rtrophic cardiomyopathy; and (4) usefulness for transgenic colony scre ening to identify markedly abnormal phenotypes.