Animal Model, Tissue/Cell Harvesting, and Phenotyping Core

核心B被限制为服务于它在我们目前的PPG中所扮演的角色，但与 要研究的狗减少了，并引入了老鼠组件和 表型鉴定作为程序的一项一般服务。核心B为三个动物提供所有动物模型 项目和核心C研究，并提供这些模型的非侵入性回波-多普勒表型分析 因此分子和细胞数据可以与完整的器官行为相关，每个模型都是 确认以反映其设计的主要生理功能。使用ECHO AS进行小鼠表型鉴定 作为终端研究，压力-体积回路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。这个 相互作用的强度由+号的数量来定性地识别。所有这三个项目 广泛应用犬模型，包括分子、细胞和亚细胞器研究 描述。在项目1中主要使用小鼠模型，但心肌细胞和心肌裂 将在项目2中检查钙循环异常和线粒体 项目3中的功能和蛋白质修改。这将使我们能够测试初级 DHF和DHF患者钙循环、电生理和线粒体功能改变的研究 不同物种的CRT条件。对于犬类模型，核心提供主要服务生成 模型，进行必要的手术，如消融和起搏器植入，以及 哈弗斯菲尔。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，并提供每个项目的表型 动物确认模型的目的是通过它的仪器和设计确实导致 同步、不同步或重新同步的高频，量化影响的大小 产生于全球和地区的商会功能，并评估这些心脏的不同步性。

Core B confinues 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 incorporafion 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 ofthis 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 ufilize 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 fissue from the model will be examined for calcium cycling abnormalifies 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 generafing the model, performing necessary procedures - i.e. ablation and pacemaker implantation, and fissue harvesfing. 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 funcfion, and assess dysynchrony in these hearts.