ASSESSMENT OF MURINE CARDIAC FUNCTION USING MR IMAGING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目旨在通过(A)在细胞和组织水平研究吸入麻醉的心脏抑制效应；(B)在正常状态下使用有创插管技术和使用变力药物(包括钙类似物或细胞内激动剂)来评估整体机械功能；以及(C)使用磁共振成像(MRI)无创性地表征小鼠的心功能(应变张量成像)，以阐明小鼠心肌力的产生和松弛的机制。 所有这些目标将在一定程度上有助于将小鼠模型完整地描述为一个潜在有用的模型(结构-功能、新陈代谢、灌流)，用于向人类推断科学结论，并最终将允许对小鼠心脏功能基因组学进行比较分析。总体而言，该项目旨在开发技术平台，以便在分子、细胞、组织和器官水平上对心血管系统进行详细研究，解决遗传线索在人类心血管疾病中的作用等基本问题，同时为在塞浦路斯发展最先进的动物成像设施建立科学平台。除了科学价值、医疗保健提供和疾病管理的价值外，这样的项目还将刺激美国、欧洲和塞浦路斯之间的流动努力，帮助吸引研究人员从事此类工作，使人们能够获得获得专业知识和资源的机会，并建立旨在将知识从美国转移到欧洲和塞浦路斯的培训计划，提高欧洲研究人员的技能和知识。在所有情况下，新的和优于现有的产品，在高科技部门的新的就业机会也将通过提高保健服务的价值和生活质量，以科学的方式直接为社会提供服务。 通过这个拟议的项目，将在分析麻醉对动物生理和心肌收缩和松弛的心脏抑制效应，研究正常状态下和钙类似物或激动剂的正性肌力干预后组织的整体机械功能和材料特性的背景下，寻求技术研究和更广泛的机动性和社会目标。从技术上讲，该项目的目标是通过拟议的研究工作，阐明心脏功能的机制和药物变力药物的应用，以及直接使用所开发的技术来实现其目标。 转基因小鼠的变化研究。此外，由于其在生理学、细胞信号、转基因、组织工程学和生物成像方面的多学科性质，将在各自的领域促进多学科的研究努力，以开发研究功能的工具和技术，分析调节心脏抑制的细胞机制，以及确定和研究导致显著心肌病和心力衰竭的关键遗传灶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims to elucidate mechanisms of myocardial force generation and relaxation in mice through (a) the study of the cardio-depressive effects of inhalational anesthesia at the cellular and tissue levels; (b) the hemodynamic assessment of global mechanical function using invasive catheterization techniques in normal states and with the use of inotropic agents, that include calcium analogs or intracellular agonists; and (c) non-invasive characterization of the murine cardiac function (strain tensor imaging) using Magnetic Resonance Imaging (MRI). All such aims will contribute in part to the complete characterization of the mouse model as a potentially useful model (structure-function, metabolism, perfusion) for extrapolation of scientific conclusions to man, and will ultimately allow comparative analyses of functional genomics in the mouse heart. Collectively, this project aims to develop the technological platform that will allow detailed studies of the cardiovascular system at the molecular, cellular, tissue and organ levels, addressing fundamental questions of the role of genetic cues in human cardiovascular disease, establishing at the same time the scientific platform for the development of a state-of-the-art animal imaging facility in Cyprus. In addition to the scientific value, the value for health care delivery and disease management, such a project will stimulate mobility efforts between USA, Europe and Cyprus and help attract investigators for the pursuit of such work, enable access opportunities to expertise and resources, and establish training programs polarised towards the transfer of knowledge from the USA to Europe and Cyprus, improving the skills and knowledge of European researchers. In all cases novel and superior products to existing ones, new employment opportunities in the high-technology sector would also offer a direct service to society, scientifically and through improvements in the value of the health care delivery and quality of life. The technical research and broader mobility and societal goals will be pursued through this proposed project, within the context of the analysis of the cardiodepressive effects of anesthesia on the animal physiology and myocardial contraction and relaxation, the study of global mechanical function and material properties of tissue at normal states and after positive inotropic intervention of calcium analogs or agonists. Technically, the project is targeted to address its objectives through the proposed research work in the elucidation of mechanisms of cardiac function and the application of pharmacological inotropic agents, as well as the direct use of the developed techniques in the study of mice with transgenic changes. Also, due to its multidisciplinary nature in physiology, cellular signalling, transgenesis, tissue engineering and bioimaging, multidisciplinary research efforts will be stimulated in the respective areas for the development of tools and techniques to study function, to analyse cellular mechanisms that mediate cardiodepression,, and to identify and study critical genetic foci that lead to prominent cardiomyopathies and heart failure.