Core--Mouse cardiac physiology

核心--小鼠心脏生理学

• 批准号: 6564972
• 负责人: JOHN JR ROSS
• 金额: $ 13.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564972
• 关键词: bioimaging /biomedical imaging; biomedical facility; catheterization; echocardiography; hamsters; hemodynamics; histology; intracardiac pressure; intravital microscopy; laboratory mouse; laboratory rat; microangiography; microsurgery; myocardium

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.

该核心单元将提供给UCSD SCOR的所有研究人员，并将应用和改进小型化血流动力学，成像和显微外科技术，用于小鼠或需要的大型啮齿动物（大鼠，仓鼠）的体内和体外生理和形态学研究，以充分表征心脏表型。用于确定心脏形态和功能的微型成像技术包括经胸超声（2-D、M-模式和多普勒超声心动图）和X射线视频血管造影术以及活体视频显微镜检查。血流动力学方法包括高保真导管尖端微压测量和通过电导法进行的用于评估心内压力的心脏容积测量，通过电导法进行的用于评估心内压力的压力-容积测量，压力-容积关系和心肌收缩性，以及麻醉闭胸动物中使用经颈动脉的逆行LV导管插入术进行的左心室（LV）舒张功能。正在开发一种方法，用于在长期使用仪器的清醒小鼠中进行长期LV导管插入术。已经在小鼠中开发了显微外科技术，以在左心室或右心室上产生慢性压力超负荷，这可用于刺激肥大或诱导心力衰竭。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）中使用。最后，将通过标准组织学方法完成心肌组织、心肌细胞或培养组织的表征，包括共聚焦显微镜和电子显微镜、伊文思蓝染料和麦胚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。