This is a Shared Instrumentation Grant request for a VisualSonics High Resolution Ultrasound Biomicroscopy System to be shared by a group of established cardiovascular investigators at Stanford University. These six co-investigators have an excellent track record in utilizing transgenic and gene knockout models of human cardiovascular disease to answer basic questions in cardiovascular development, cell signaling, and cardiovascular pathophysiology. Examples of gene targeted animals under current investigation include those with alterations of: a and b-adrenergic receptors, protein kinase C isoenzymes, the apelin/APJ-receptor, microtubule-associated protein light chain 3 (LC3), the calcium binding protein S100A4/Mtsl, and bone morphogenetic protein receptors (BMP-R) I and II. Studies are also underway of transplanted embryonic stem cells and cardiomyocytes overexpressing connexin-43 in murine models of ischemic injury. Models currently being studied include genetic and toxic dilated cardiomyopathy, cardiac hypertrophy, ischemia/reperfusion injury, preconditioning, and cardiac allograft rejection. Echocardiographic assessment of cardiac function is thus critically important to the success of each investigator's research program; currently these assessments are being performed utilizing equipment developed for imaging human neonates. Recent developments in high frequency ultrasound (12.5-49 mHz transducers) have allowed imaging of the adult murine heart with accuracy previously unobtainable and have also allowed imaging of the neonatal and fetal murine heart, providing a major advance for studies of abnormal cardiac development. There is a strong institutional commitment to support the High Resolution Ultrasound System, which will be based in the Stanford Murine Cardiovascular Phenotyping Core, located in the Principal Investigator's lab. This facility has been providing Stanford investigators with physiologic phenotyping services for 10 years: acute and chronic vascular cannulation, telemetry, conductance PV loop analysis, exercise physiology, metabolism, tissue bath studies, and echocardiography. This lab has been at the forefront in developing murine phenotyping techniques, including one of the first to standardize non-restrained, non-anesthetized cardiovascular measurements and to develop murine treadmill exercise protocols. Being an integral part of this core facility will guarantee the quality and reproducibility of High Resolution Ultrasound studies as well as utilize a proven mechanism to provide other qualified Stanford investigators access to this equipment.
