Core--Mouse cardiac physiology

这一核心单元将向UCSD SCOR的所有研究人员提供，并将应用和改进微型血流动力学、成像和显微外科技术，用于在小鼠或需要时对较大啮齿动物(大鼠、仓鼠)进行体内和体外生理和形态研究，以便全面确定心脏表型。用于确定心脏形态和功能的微型化成像技术包括经胸超声(二维、M型和多普勒超声心动图)、X射线血管成像和活体视频显微镜。血流动力学方法包括高保真导管尖端微量测压和电导法测量心内压，电导法测量心内压、压力-容量关系和心肌收缩能力，以及经颈动脉逆行LV插管麻醉开胸动物的左心室(LV)的舒张功能。一种方法正在开发中，用于在有慢性器械的清醒小鼠中进行慢性左心室插管。已经在小鼠身上开发了显微外科技术，在左或右心室产生慢性压力超负荷，这可能被用来刺激肥厚或导致心力衰竭。显微外科基因转移方法正在开发中，并将在成年动物(小鼠和较大的啮齿动物)上使用。最后，心肌组织、心肌细胞或培养组织的特征将通过标准的组织学方法完成，包括共聚焦显微镜和电子显微镜、伊文思蓝染色和麦芽凝集素染色以评估肌膜完整性，以及各种蛋白质的免疫染色，包括跨膜细胞外基质和细胞骨架蛋白。

This core unit will be available to all investigators on the UCSD SCOR and will apply and improve miniaturized hemodynamic, imaging and microsurgical techniques for in vivo and in vitro physiological and morphological studies in mice, or larger rodents as needed (rats, hamsters), in order to fully characterize cardiac phenotypes. Miniaturized imaging techniques for determining cardiac morphology and function include transthoracic ultrasound (2-D, M-mode and Doppler echocardiography) and x-ray videoangiography, and intravital videomicroscopy. Hemodynamic methods include high-fidelity catheter tip micromanometry and cardiac volume measurements by the conductance method for assessing intracardiac pressures, pressure-volume measurements by the conductance method for assessing intracardiac pressures, pressure volume relations and myocardial contractility, as well as diastolic function of the left ventricle (LV), in anesthetized closed- chest animals using retrograde LV catheterization via the carotid artery. A method is under development for chronic LV catheterization in chronically instrumented conscious mice. Microsurgical techniques have been developed in mice to produce chronic pressure overload on either the left or right ventricle which can be used to stimulate hypertrophy or to induce heart failure. Microsurgical gene transfer methods are being developed and will be available in the adult animal (mice and larger rodents). Finally, characterization of myocardial tissue, myocardial cells or cultured tissue will be accomplished by standard histologic methods, including confocal microscopy and electron microscopy, Evans blue dye and wheat germ agglutinin staining to assess sarcolemmal integrity, and immunostaining of various proteins, including transmembrane extracellular matrix and cytoskeletal proteins.