Animal and Clinical Core
动物和临床核心
基本信息
- 批准号:10705687
- 负责人:
- 金额:$ 66.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-20 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAnatomyAnimal ModelAnimalsApoptosisApoptoticBiochemicalBioenergeticsBiologicalBiological Specimen databaseBiomechanicsBlood PressureBlood VesselsBlood flowBlood specimenCardiopulmonaryCardiopulmonary BypassCardiovascular systemCell LineCell ProliferationCellsChildChildhoodClinicalClinical DataComplexCongenital Heart DefectsCoupledDataData AnalysesDatabasesDedicationsDevelopmentDisease ProgressionEndotheliumEnsureEquipmentEvaluationFetal SheepHumanHuman ResourcesIn VitroInfantLaboratoriesLifeLigationLungMeasurementMetabolicMicrofluidicsMitochondriaModelingMonitorMorphologyNitrogenNitrogen OxidesOperative Surgical ProceduresOxygenPathologicPathway interactionsPatientsPatternPeptidesPeriodicityPerioperativePeripheralPhenotypePhysiologic intraventricular pressurePhysiologicalPost-Translational Protein ProcessingPostoperative PeriodPreparationProceduresProcessProliferatingPulmonary artery structureReproducibilityResearchResearch InstituteResearch PersonnelResourcesRunningSamplingSecureServicesSheepShunt DeviceSmooth Muscle MyocytesStandardizationStretchingSurgical ModelsSystemTechniquesTissuesTrainingTubeVariantVascular Endothelial CellWorkangiogenesisanimal morbidityanimal mortalitybiobankclinical databaseclinically relevantcongenital heart disordercost efficientdesigndisorder subtypeexperienceexperimental studyfetalfetal cardiac surgeryhemodynamicsin uteroin vivoin vivo imagingindexinginnovationlung injurymechanical forcemechanotransductionneonatenovelpostnatalpressurepulmonary vascular disorderpulmonary vascular remodelingrepairedscreeningshear stresssheep modeltargeted treatment
项目摘要
ABSTRACT: With the use of fetal cardiac surgical techniques, Core C is designed to provide PPG investigators
with rigorously defined and reproducible novel ovine models of congenital heart disease (CHD). To this end,
Core C will comprehensively generate, manage and provide all animal-related experiments, resources, and
expertise. In addition, Core C will obtain peri-operative blood samples from neonates, infants, children, and
adults with a wide range of differing congenital heart defects, to be utilized by PPG investigators. A secure
database is already established that contains banked samples and clinical data on >300 patients. In this context,
Core C will be defined by providing six services: 1) Ovine models of CHD. This will include our well-established
Shunt model and our newly created LPA ligation model. Tissues (peripheral lung and isolated vessels) and
primary pulmonary artery endothelial and smooth muscle cells (both proximal and microvascular) will be
available to PPG investigators. 2) Acquisition and analysis of data. This will include the evaluation of
cardiopulmonary hemodynamics, pulmonary vascular reactivity (both in vivo and in vitro), the assessment of
pulmonary vascular remodeling, advanced in vivo imaging, the effect of cardiopulmonary bypass on
hemodynamics and vascular function, and the effect of different therapies. 3) Biochemical, proliferation,
apoptosis, and angiogenesis determinations. This will include the measurement of various reactive oxygen and
nitrogen species of oxygen or nitrogen oxide in vascular cells and tissues, indices of cell proliferation, apoptosis,
and tube formation. 4) The in vitro assessment of differing biomechanical forces. This includes the utilization of
a novel microfluidic chamber (UCSD) that allows the simultaneous and independent variation of pressure, cyclic
stretch, and flow-induced shear stresses on the vascular endothelial cells. 5) Use of the CAR peptide to target
therapeutics to the damaged pulmonary endothelium. To reduce the potential of off-target effects, we will utilize
IV co-delivery of our therapies with the CARSKNKDC (CAR) peptide. 6) A bio-repository and corresponding
clinical database of neonates, infants, children, and adults with CHD. Blood samples from patients with CHD
will be obtained before and after surgical repair for human confirmation of aberrant pathways initially identified
in animals and for metabolic screening. Correlation between the identified aberrations, with the type of CHD (+/-
flow; +/- pressure), and degree of pre-operative and post-operative pulmonary vascular disease will be sought.
Core C will enhance the scientific work for all three projects by assuring that all animal models are standardized
and performed in a uniform manner by highly experienced and trained personnel. Investigators who have had
many years of experience using these techniques run Core C. They have developed or adapted several of the
techniques and applied them to perform physiological studies in in vitro and in vivo systems. As a central
dedicated analytical resource Core C will ensure these analyses are also carried out in a cost-efficient manner
with minimal animal morbidity and mortality.
摘要:Core C 旨在利用胎儿心脏手术技术为 PPG 研究人员提供
具有严格定义和可重复的新型绵羊先天性心脏病(CHD)模型。为此,
Core C将全面生成、管理和提供所有与动物相关的实验、资源和
专业知识。此外,Core C 还将获取新生儿、婴儿、儿童和儿童的围手术期血液样本。
患有各种不同先天性心脏缺陷的成年人,供 PPG 研究人员使用。一个安全的
数据库已经建立,其中包含超过 300 名患者的存储样本和临床数据。在此背景下,
核心 C 将通过提供六项服务来定义:1)CHD 的 Ovine 模型。这将包括我们完善的
分流模型和我们新创建的 LPA 连接模型。组织(周围肺和孤立的血管)和
原代肺动脉内皮细胞和平滑肌细胞(近端和微血管)将
可供 PPG 调查人员使用。 2)数据采集和分析。这将包括评估
心肺血流动力学、肺血管反应性(体内和体外)、评估
肺血管重塑、先进的体内成像、体外循环对肺血管的影响
血流动力学和血管功能,以及不同疗法的效果。 3) 生化、增殖、
细胞凋亡和血管生成测定。这将包括测量各种活性氧和
血管细胞和组织中氧或氮氧化物的氮形态,细胞增殖、凋亡指数,
和管的形成。 4)不同生物力学力的体外评估。这包括利用
一种新型微流体室(UCSD),允许同时且独立地改变压力、循环
血管内皮细胞上的拉伸和流动引起的剪切应力。 5)利用CAR肽靶向
针对受损肺内皮的治疗。为了减少脱靶效应的可能性,我们将利用
我们的疗法与 CARSKNKDC (CAR) 肽一起进行静脉注射。 6) 生物储存库及相应的
患有 CHD 的新生儿、婴儿、儿童和成人的临床数据库。冠心病患者的血液样本
将在手术修复之前和之后获得,以对最初确定的异常途径进行人体确认
在动物中和用于代谢筛查。已识别的像差与 CHD 类型之间的相关性 (+/-
流动; +/- 压力),以及术前和术后肺血管疾病的程度。
核心 C 将通过确保所有动物模型标准化来加强所有三个项目的科学工作
并由经验丰富且训练有素的人员以统一的方式执行。调查人员曾经有过
使用这些技术运行 Core C 的多年经验。他们已经开发或改编了其中的几个
技术并将其应用于体外和体内系统的生理研究。作为中央
专用分析资源 Core C 将确保这些分析也以经济高效的方式进行
动物发病率和死亡率最低。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('JEFFREY R FINEMAN', 18)}}的其他基金
Endothelial mechanotransduction and metabolic remodeling
内皮力转导和代谢重塑
- 批准号:
10468115 - 财政年份:2020
- 资助金额:
$ 66.18万 - 项目类别:
Endothelial mechanotransduction and metabolic remodeling
内皮力转导和代谢重塑
- 批准号:
10705691 - 财政年份:2020
- 资助金额:
$ 66.18万 - 项目类别:
Development of an oxygen delivery biotherapeutic for the preservation of myocardial function during pediatric cardiopulmonary bypass
开发用于在儿科体外循环期间保存心肌功能的氧气输送生物治疗药物
- 批准号:
10761664 - 财政年份:2017
- 资助金额:
$ 66.18万 - 项目类别:
Development of an oxygen delivery biotherapeutic for the preservation of myocardial function during pediatric cardiopulmonary bypass
开发用于在儿科体外循环期间保存心肌功能的氧气输送生物治疗药物
- 批准号:
9256317 - 财政年份:2017
- 资助金额:
$ 66.18万 - 项目类别:
Research Training in Pediatric Critical Care Medicine
儿科重症监护医学研究培训
- 批准号:
8452072 - 财政年份:2006
- 资助金额:
$ 66.18万 - 项目类别:
Research Training in Pediatric Critical Care Medicine
儿科重症监护医学研究培训
- 批准号:
8267026 - 财政年份:2006
- 资助金额:
$ 66.18万 - 项目类别:
Research Training in Pediatric Critical Care Medicine
儿科重症监护医学研究培训
- 批准号:
7232428 - 财政年份:2006
- 资助金额:
$ 66.18万 - 项目类别:
Research Training in Pediatric Critical Care Medicine
儿科重症监护医学研究培训
- 批准号:
9038390 - 财政年份:2006
- 资助金额:
$ 66.18万 - 项目类别:
Research Training in Pediatric Critical Care Medicine
儿科重症监护医学研究培训
- 批准号:
10593956 - 财政年份:2006
- 资助金额:
$ 66.18万 - 项目类别:
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