Cardiovascular and metabolic phenotyping of rodents

啮齿动物的心血管和代谢表型

• 批准号: 7732122
• 负责人: Sandor Batkai
• 金额: $ 11.85万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732122
• 关键词: Acute; Alcoholic Liver Diseases; Alcohols; Anesthesia procedures; Animal Model; Animals; Arts; Biochemical; Blood; Blood Pressure; Blood flow; Body Temperature; Breeding; Cardiac; Cardiovascular system; Catheters; Characteristics; Chronic; Collaborations; Collection; Condition; Core Facility; Devices; Diet; Disease; Disease model; Eating; Echocardiography; Endocannabinoids; Energy Metabolism; Environmental air flow; Evaluation; Fatty Liver; Functional disorder; Genetic; Genotype; Goals; Heart; Heart Rate; Homeostasis; Hypertension; Hypotension; Image; Implant; Indirect Calorimetry; Intervention; Intramural Research Program; Invasive; Left; Life; Longitudinal Studies; Maintenance; Measurement; Measures; Mechanics; Metabolic; Metabolic syndrome; Methodology; Methods; Microscopic; Modeling; Monitor; Motor Activity; Mouse Strains; National Institute on Alcohol Abuse and Alcoholism; Obesity; Operative Surgical Procedures; Pharmaceutical Preparations; Phenotype; Physiologic intraventricular pressure; Physiological; Process; Property; Pump; Regulation; Relative (related person); Research; Research Project Grants; Resolution; Rodent; Rodent Model; Role; Signal Transduction; Structure; System; Tail; Techniques; Telemetry; Therapeutic; Time; Tissue Sample; Tissues; Today; Ventricular; alcohol research; blood pressure regulation; hemodynamics; human disease; implantation; in vivo; metabolic abnormality assessment; mouse model; non-invasive system; pressure; vascular bed

The Phenotyping Core Facility is currently focused on the characterization of cardiometabolic phenotype in relevant animal models by using standardized, high quality functional analysis of blood pressure and flow regulation, cardiac and metabolic functions. State-of-the art methodology used in these studies include monitoring of systemic blood pressure, heart rate and blood flow in genetically altered or pharmacologically manipulated animals using non-invasive tail cuff method or telemetry systems, or using implanted microcatheters and flow probes in anesthetized animals. Left ventricular hemodynamic function is assessed by using non-invasive echocardiography or the invasive Millar Pressure-Volume Catheter Systems (MPVS). The Vevo 770 echocardiography imaging system gives the ability to image in vivo the functionality of small animal anatomical and physiological features as well as to measure blood flow. The non-invasive system allows longitudinal studies. The system has a spatial resolution down to 30 microns, the highest resolution available in real-time today. This resolution permits to study extremely small physiological structures, such as vascular beds and the imaging of living tissue and blood flow with near-microscopic resolution. The MPVS allows simultaneous and continuous high-fidelity monitoring of left ventricular pressure and relative volume in the intact, beating hearts of anesthetized animals. Using the MPVS systems, intraventricular pressure and volume signals can be plotted against each other in real time, generating the characteristic pressure-volume (P-V) loops in normal or diseased conditions and allow the determination of load dependent and independent parameters of cardiac contractile function. With the MPVS, P-V loops may be captured during pharmacological, therapeutic, and hemodynamic interventions, allowing comprehensive evaluation of the fundamental mechanical properties of the heart. Precise, non-invasive, quantitative assessment of energy homeostasis in rodent models is critical to study metabolic function in models of obesity and fatty liver, including alcoholic liver disease. The Core also provides comprehensive monitoring of food intake, energy expenditure (indirect calorimetry), locomotor activity and body temperature measurement by telemetry for animals on various types of diets. In addition to the functional measurements, collections of blood and tissue samples for biochemical, histological, etc. analysis are available. The Cores surgical suite allows carrying out a variety of non-survival and survival surgical techniques, including the use of different type of anesthesia, assisted ventilation, and surgical implantation of drug filled mini pumps, catheters and telemetry devices. Finally the core is involved in the breeding and maintenance of a variety of genetically altered mouse strains and their genotyping. The research projects carried out in this period in collaboration with the core include the study of the role of the endocannabinoid system in blood pressure regulation in hypertension or in various disease models associated with hypotension, the study of genetic factors and potential pharmacological targets of the impaired cardiac function in chronic or acute models of the failing heart, and analyses of changes in energy metabolism in mouse models of obesity, metabolic syndrome and alcoholic liver disease.

目前，通过使用标准化的，高质量的功能分析，血压和流动调节，心脏和代谢功能，表征核心设施集中在相关动物模型中心脏代谢表型的表征上。这些研究中使用的最新艺术方法包括使用非侵入性尾袖方法或遥测系统监测系统性血压，心率和血液流动，或者使用植入的微心理处理器和麻醉动物中的流量探针。通过使用非侵入性超声心动图或侵入性Millar压力卷导管系统（MPV）评估左心室血液动力学功能。 VEVO 770超声心动图成像系统具有在体内形象图像小动物解剖学和生理特征的功能以及测量血流的能力。非侵入性系统允许纵向研究。该系统的空间分辨率低至30微米，这是当今实时可用的最高分辨率。该分辨率允许研究极小的生理结构，例如血管床以及生物组织和血流的成像，并通过接近微观的分辨率进行。 MPV允许对完整的左心室压力和相对体积的同时且连续的高保真监测，从而跳过麻醉动物的心脏。使用MPVS系统，可以实时绘制室内压力和体积信号，从而在正常或患病条件下产生特征压力量（P-V）环，并允许确定载荷依赖性和独立的收缩功能的参数。使用MPV，可以在药理，治疗和血液动力学干预期间捕获P-V环，从而可以全面评估心脏的基本机械性能。啮齿动物模型中能量稳态的精确，非侵入性，定量评估对于研究肥胖和脂肪肝模型（包括酒精性肝病）的代谢功能至关重要。该核心还提供了对食物摄入，能量消耗（间接量热法），运动活性和体温测量各种饮食的动物测量的全面监测。除功能测量外，还可以分析生化，组织学等的血液和组织样品的收集。核心手术套件允许进行多种非生存和生存手术技术，包括使用不同类型的麻醉，辅助通风以及对药物填充的迷你泵，导管和遥测设备的手术植入。最后，核心参与了各种遗传改变的小鼠菌株及其基因分型的繁殖和维持。 在此期间与核心合作进行的研究项目包括研究内源性大麻素系统在血压调节高血压中的作用，或在与低血压相关的各种疾病模型中，对遗传因素的研究以及心脏或急性心脏疾病模型中心脏功能受损的潜在药理目标的研究以及能量疾病的疾病模型的变化，并分析了肥胖症中的疾病的变化。