The mouse and surgery core will interface with the other Cores to provide two major services to all four projects in this PPG. Specifically, this Core Unit will be responsible for providing: 1) surgical mouse models of cardiac hypertrophy and heart failure (HF), and 2) complete and comprehensive cardiovascular phenotyping of all mouse models and corresponding control mice detailed throughout this PPG application. Surgical Mouse Models include: A) Surgically induced pressure overload hypertrophy and HF using the technique of transverse aortic constriction (TAG), both short and long-term B) Providing a mouse model of HF via coronary artery occlusion (myocardial infarction, Ml) C) Providing a mouse model of cardiac ischemia/reperfusion injury (I/R) via acute coronary occlusion D) Surgical implantation of Azlet mini-osmotic pumps for chronic drug treatment Comprehensive Mouse Cardiovascular Phenotyping include: A) An in-depth assessment of mouse in vivo cardiac function via echocardiography including serial measurements B) Assessment of in vivo cardiac pressures and hemodynamic measurements via Millar catheterization of the left ventricle C) Ex vivo measurements of heart function via a Langendorff perfusion system D) Assessment of conscious blood pressure and EKG using telemetry This shared resource will provide a highly efficient way to conduct such studies in a centralized wellequipped location and all Projects will utilize this space. Dr. Gao who heads the Physiology/Surgery Core in the Center for Translational Medicine has considerable expertise in mouse surgical models especially Ml and I/R injury1""""""""10. He has already collaborated and aided all four Project Leaders of this PPG in the gathering of preliminary data presented in each Project. He has recently developed the murine TAG model after visiting the laboratory of Dr. Howard Rockman, a long-time collaborator of Dr. Koch. This methodology, as described below, has been successfully transferred to the Center of Translational Medicine.
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