This proposal requests funds to aid in the acquisition the Vevo 770 High Resolution Imaging System, an ultrasound machine dedicated to characterizing mouse and rat models of human cardiovascular disorders. In recent years, the development of genetically-altered mice has enhanced our understanding of the basic mechanisms underlying cardiac physiology and pathological states. Echocardiography has emerged as a crucial noninvasive technique to assess the left ventricular (LV) size and function of small animals, reducing the number of animals necessary to define a cardiac phenotype and allowing for serial evaluation in the same animal. The Vevo 770 will be a dedicated research echocardiogram, easily available for ongoing studies, and will be kept inside the viral-antibody free (barrier) rodent facility, allowing for serial evaluation of genetically-modified animals. The high spatial resolution of the Vevo 770 permits serial evaluation of structures which are not visualized by conventional echocardiograms, such as the right ventricle, neonatal hearts, great vessels. The right ventricular size and function will be followed serially in models of lung injury to assess the efficacy of novel therapies including inhaled nitric oxide (NO) (Dr. Zapol) and in models of pulmonary hypertension associated with mutations in the gene encoding BMPR-II (Dr. Bloch). Left ventricular mass and function will be assessed precisely and repeatedly in models of pressure-overload to gain insights into the role of nitric oxide synthase 3 (Dr. Bloch) and cytoskeletal proteins (Dr. Chien). Assessment of rodent LV remodeling after myocardial infarction will allow better understanding of the mechanisms involved in this process (Dr. Levine). Serial follow-up of the aorta and carotids will help to determine the impact of NO synthases on atherosclerosis (Dr. Huang) and will provide insights into the role of inflammation in vascular aneurysms formation (Dr. Gerszten). Finally, detecting small quantities of echocardiographic contrast may enable new ways to image stem cells (Dr. Hajjar). Relevance. The Vevo770 is an ultrasound machine dedicated to small animals and capable of noninvasively imaging very fine cardiac or vascular structures. We will use this machine to better understand the pathways involved in pulmonary and systemic high blood pressure, atherosclerosis, heart failure, as well as to attempt to image stem cells. ? ? ?
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