SMALL ANIMAL ECHOCARDIOGRAPHY SYSTEM

基因操作已成为阐明所有生物学生理和病理生理机制的有力工具，特别是在心血管功能和结构的研究中获得了重要的立足点。这种工作的核心策略是产生转基因动物，这最常在小鼠身上完成，对小鼠进行广泛的基因组绘制使得这项工作可行。然而，这项研究通过超声心动图设备和技术的适应解决了这一局限性，这些设备和技术允许对小鼠轻度镇静期间的心功能进行全面评估。迄今为止的工作包括对肌酸激酶、血管紧张素受体敲除的转基因小鼠的心功能研究，以及（肥厚型心肌病表型）；主动脉束带所致心室后负荷增加的大鼠。这些研究是在儿科超声心动图和血流动力学研究实验室进行的，该实验室的主任和工作人员在制定必要的程序和开展工作方面提供了巨大的帮助。然而，随着技术的掌握，调查人员的需求急剧上升，设备的使用受到严重限制。因此，本提案为最先进的超声心动图单元寻求资金支持，该单元专门用于小动物（小鼠和大鼠）心脏结构和功能的非侵入性体内采集和分析。拟议的设备将为七名调查人员组成的核心小组提供服务。拟议的设备将为七名调查人员组成的核心小组提供服务。拟议的单位将设在心血管肺研究实验室，由专门的工作人员和一个咨询委员会管理，并与迄今为止开展工作的超声心动图人员进行持续咨询和协商。

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.