The function of the Surgery and Physiology Core (Core B) is to provide the expertise, equipment, and facilities needed for all of the in vivo murine studies. Specifically, Core B will be responsible for all surgical procedures (coronary artery occlusion/reperfusion and CPC delivery), echocardiographic analyses, invasive hemodynamic studies, and maintenance and genotyping of transgenic and knockout mouse lines. Accurate physiological measurements and surgical procedures in mice represent technically demanding tasks that cannot, and should not, be attempted in every laboratory, but rather should be performed by a group of dedicated investigators who focus on studies in mice and thereby acquire extensive experience with this difficult model. One of the main advantages of this Program Project is that it provides all four Proiects with access to complex and technically challenging in vivo mouse models of mvocardial infarction (Ml) and ceil therapy, expert physiology and surgery, and state-of-the-art technigues that otherwise would not be available to these investigators. This is a major benefit to all investigators. Core B consists of a team of skilled, highly- experienced investigators who have worked together cohesively for many years focusing exclusively on murine studies (they have performed >16.000 surgical procedures in mice), have developed and perfected murine models of Ml and cell therapy utilizing state-of-the-art facilities and equipment, and have collaborated extensively with the other investigators in this PPG. An important feature of Core B is that it will use a new technique for delivering CPCs - intracoronary infusion in the mouse, which has never been used before in this species. Compared with standard intramyocardial injection, intracoronary infusion is much more clinically relevant. Furthermore, it enables uniform distribution of CPCs throughout the infarct and in the noninfarcted region, which is not possible with intramyocardial injection, and produces superior results, as shown by our data. Another feature is that all echocardiographic and hemodynamic analvses will be performed off-line by blinded observers. The capacity of the Core has been tested in the preparation of this submission. To produce the preliminary data needed for this application. Core B has operated upon >300 mice and performed 231 studies of CPC transplantation, 390 echocardiographic studies, and 108 hemodynamic studies. All of this has been done in the past 10 months. These numbers eloquently illustrate the research output that the Core can produce.

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Heart, Lung, and Blood Program Project Review Committee (HLBP)
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University of Louisville
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