Genetic manipulation has become a powerful tool for elucidation of physiologic and pathophysiologic mechanisms in all of biology and is specifically gaining a major foothold in investigations of cardiovascular function and structure. The central strategy in such work is the generation of transgenic animals which is most commonly done in mice for which extensive mapping of the genome makes this work feasible. However, this addressed this limitation by adaptation of echocardiographic equipment and techniques which permits comprehensive assessment of cardiac function during light sedation in mice. Work to date has encompassed studies of cardiac function in transgenic mice with knock-outs of creatine kinases, angiotensin receptors, and (with a hypertrophic cardiomyopathy phenotype); and in rats with increased ventricular afterload induced by aortic banding. These studies have been done in the Pediatric Echocardiography and Hemodynamic Research Laboratory Facility of which the Director and Staff have been of enormous help in development of requisite procedures and conduct of the work. However, with the techniques now in hand, demand by investigators has risen steeply and access to equipment has become seriously limiting. Accordingly, this proposal seeks funding for a state-of-the-art echocardiographic unit uniquely suited for, and dedicated to, non- invasive in vivo acquisition and analysis of cardiac structure and function in small animals (mice and rats). The proposed equipment would serve a core group of seven investigators. The proposed equipment would sere a core group of seven investigators. The proposed unit would be housed in the Cardiovascular Pulmonary Research Laboratory and managed by dedicated staff and an advisory committee with ongoing advice and consultation with echocardiography personnel with whom the work to date has been conducted.
