Animal Model, Tissue/Cell Harvesting, and Phenotyping Core

核心B继续发挥它在我们目前的PPG中所扮演的角色，但随着要研究的狗的总数减少，并引入了鼠标组件并将表型鉴定作为一项一般服务纳入该计划。核心B为三个项目提供了所有动物模型，核心C进行了研究，并提供了这些模型的非侵入性回波-多普勒表型分析，以便分子和细胞数据可以与完整的器官行为相关，并且每个模型都得到确认，以反映其设计的主要生理功能。使用ECHO的小鼠表型分析以及终端研究压力-体积环分析也将是该核心的职责。表1提供了核心B服务与项目和其他核心服务的一般交互作用。相互作用的强度由+号的数量来定性地识别。这三个项目都广泛地利用了犬类模型，描述了分子、细胞和亚细胞器的研究。项目1主要使用小鼠模型，但项目2将检查模型中的心肌细胞和心肌组织的钙循环异常，项目3将检查线粒体功能和蛋白质修饰。这将使我们能够测试跨物种DHF和CRT条件下钙循环、电生理和线粒体功能变化的主要发现的一致性。对于犬模型，核心提供主要服务，生成模型，执行必要的程序-即消融和起搏器植入，以及组织采集。对于小鼠模型，核心将根据需要提供全面的菌落维护、遗传监测和基因分型，并使组织和细胞可用于其他项目。核心的第二个主要作用还服务于所有项目，并提供每个动物的表型，以确认其仪器和设计所预期的模型确实导致了同步、不同步或重新同步的心衰，量化了对全球和区域心脏功能产生的影响的程度，并评估了这些心脏的不同步。

Core B continues to serve the role it played in our present PPG, but with the total number of dogs to be studied reduced, and with introduction of a mouse component and incorporation of phenotyping as a general service to the program. Core B provides all animal models to the three Projects, and Core C studies, and provides non-invasive echo-Doppler phenotyping of these models so that molecular and cellular data can be related to intact organ behavior and each model is confirmed to reflect the primary physiology it is designed to do. Mouse phenotyping using echo as well as terminal study pressure-volume loop analysis will also be the responsibility of this Core. Table 1 provides the general interaction of Core B services to the projects and other core. The strength of the interaction is identified qualitatively by the number of + signs. All three of the projects extensively utilize the canine model, with both molecular, cellular and sub-organelle studies described. The mouse model is primary utilized in Project 1, but myocytes and myocardial tissue from the model will be examined for calcium cycling abnormalities in Project 2 and for mitochondrial function and protein modifications in Project 3. This will enable us to test the consistency of primary findings in calcium cycling, electrophysiology, and mitochondrial function changes between DHF and CRT conditions across species. For the canine model, the core provides primary services generating the model, performing necessary procedures - i.e. ablation and pacemaker implantation, and tissue harvesting. For the mouse models, the core will provide overall colony maintenance, genetic monitoring and genotyping as required, and make tissues and cells available to the other Projects. The second major role of the Core also services all Projects, and is to provide phenotyping of each animal to confirm that the model intended by its instrumentation and design indeed resulted in synchronous, dyssynchronous, or resynchronized HF, quantify the magnitude of the effects generated on global and regional chamber function, and assess dysynchrony in these hearts.