Cardiovascular and metabolic phenotyping of rodents

啮齿动物的心血管和代谢表型

• 批准号: 7969888
• 负责人: Sandor Batkai
• 金额: $ 15.12万
• 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/7969888
• 关键词: Acute; Alcoholic Liver Diseases; Alcohols; Animal Model; Animals; Arts; Biochemical; Blood; Blood Pressure; Blood flow; Body Temperature; Breeding; Cardiac; Cardiomyopathies; Cardiovascular system; Catheters; Characteristics; Chronic; Collaborations; Core Facility; Development; Diet; Disease; Eating; Echocardiography; Endocannabinoids; Energy Metabolism; Evaluation; Fatty Liver; Genetic; Heart; Heart Rate; Homeostasis; Hypertension; Image; Indirect Calorimetry; Intervention; Intramural Research Program; Intraventricular; Left; Maintenance; Measures; Mechanics; Metabolic; Metabolic syndrome; Methodology; Methods; Modeling; Monitor; Motor Activity; Mouse Strains; National Institute on Alcohol Abuse and Alcoholism; Obesity; Phenotype; Physiologic intraventricular pressure; Physiological; Preventive; Process; Property; Relative (related person); Rodent; Rodent Model; Role; Signal Transduction; System; Techniques; Telemetry; Therapeutic; Time; Tissue Sample; Ventricular; hemodynamics; human disease; in vivo; metabolic abnormality assessment; mouse model; non-invasive monitor; pressure; research study

The Phenotyping Core Facility has been focusing on in vivo cardiovascular and metabolic analyses in rodents using standardized, high quality, state-of-the-art techniques. The methodology used in these animal studies include non-invasive monitoring of systemic blood pressure, heart rate and blood flow in genetically altered or pharmacologically manipulated animals. Left ventricular hemodynamic function is assessed by the invasive Millar Pressure-Volume Intraventricular Catheter Systems (MPVS) and/or non-invasive echocardiography. The MPVS allows simultaneous and continuous high-fidelity monitoring of left ventricular pressure and relative volume in the intact heart of anesthetized animals. Intraventricular pressure and volume signals generate in real time the characteristic pressure-volume (P-V) loops, which are used to determine load-dependent and -independent parameters of cardiac contractile function in normal and disease conditions. The P-V loops may be captured during pharmacological, therapeutic, and hemodynamic interventions, allowing comprehensive evaluation of the fundamental mechanical properties of the heart. The Vevo 770 echocardiography imaging system provides the ability to image in vivo the functionality of small animal anatomical and physiological features. 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. Methods for the comprehensive monitoring of food intake, energy expenditure (indirect calorimetry), locomotor activity and core body temperature by telemetry have been established and experiments have been conducted in animals on various types of diets. Blood and tissue samples are routinely collected for genetic, biochemical and histological analyses. In addition, the core has been involved in the breeding and maintenance of the various genetically altered mouse strains. Projects carried out in collaboration with the core during this period include the study of the role of endocannabinoid system in hypertension and in cirrhotic cardiomyopathy, 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.

使用标准化的高质量，最先进的技术，表型核心设施一直集中在啮齿动物中体内心血管和代谢分析上。这些动物研究中使用的方法包括对遗传改变或药理操纵动物的全身血压，心率和血流的非侵入性监测。左心室血液动力功能通过浸润性米拉压力卷室内导管系统（MPV）和/或非侵入性超声心动图评估。 MPV允许对麻醉动物完整心脏中左心室压力和相对体积的同时且连续的高保真监测。脑室内压力和体积信号实时生成特征压力卷（P-V）回路，该回路用于确定正常和疾病条件下心脏收缩功能的载荷依赖性和非依赖性参数。可以在药理，治疗和血液动力学干预期间捕获P-V回路，从而可以全面评估心脏的基本机械性能。 VEVO 770超声心动图成像系统提供了在体内图像小动物解剖和生理特征的功能的能力。 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。已经建立了对食物摄入，能量消耗（间接量热法），运动活性和核心体温的全面监测方法，并已建立了遥测，并在动物的各种饮食中进行了实验。 通常收集血液和组织样品，以进行遗传，生化和组织学分析。 此外，核心还参与了各种遗传改变的小鼠菌株的繁殖和维持。 在此期间，与核心合作进行的项目包括研究内源性大麻素系统在高血压和肝硬化心肌病中的作用，对遗传因素的研究以及心脏功能受损的遗传因素和潜在的药理学靶标在失败心脏模型中的慢性或急性急性模型中，以及在肥胖症中的生物疾病中的能量分类症的变化。