Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
基本信息
- 批准号:10092300
- 负责人:
- 金额:$ 69.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:Adrenergic AgentsAgitationAnatomyArrhythmiaAutonomic nervous systemBindingBlood VesselsBlood flowBrainCardiacCardiac MyocytesCardiac OutputCardiovascular PhysiologyCardiovascular systemCatecholaminesCell modelCellsClinicalCollaborationsCollectionCrystallizationDataDevelopmentDoctor of PhilosophyElectric StimulationElectrophysiology (science)EnsureEventFrightGoalsHeartHeart DiseasesHeart failureHypertensionIndividualIon ChannelLifeLinkMindModelingMolecularMyocardiumNatureNerveNervous system structureOrganOutputPainPatient-Focused OutcomesPatientsPeripheral NervesPharmaceutical PreparationsPharmacotherapyPhysiologicalPhysiologyProblem SolvingProteinsProtocols documentationRecording of previous eventsRegulationResearch PersonnelRoleSignal TransductionSignaling ProteinSmooth MuscleStrokeSynapsesSynaptic ReceptorsTestingTherapeutic InterventionTimeTissuesUncertaintyVascular DiseasesVascular Smooth MuscleYinaffectionarmbasebody systemcomputational suitecomputerized toolsdesignexperimental studyflexibilityheart rhythmhemodynamicsimprovedindividual responseinsightneural circuitneural modelneuronal circuitryneuroregulationnovelpleasurepopulation basedpredictive toolspreventresponsesexsimulationsynergismtoolverification and validation
项目摘要
Project Summary
In 1628 William Harvey wrote, “Every affection of the mind that is attended with either pain or
pleasure, hope or fear, is the cause of an agitation whose influence extends to the heart.”
Despite centuries of recognition of the fundamental connection between the brain and heart,
there is still very poor understanding of the role of autonomic control in normal cardiac control
and in the paroxysmal nature of life threatening cardiac events. To predict the mechanisms
underlying the interaction between nervous system discharge and the resultant emergent
cardiac and vascular events would finally allow for individual identification and specific targeting
of arrhythmia provoking conditions by drugs or even by direct electrical stimulation. We propose
to develop the Neurocardiovascular Simulator suite to solve this problem. The proposed
simulator is unparalleled, as it will integrate anatomical and functional data ranging from the
atomic level for ion channels and key signaling proteins to subcellular to cellular, organ, and
systems data and simulations. Importantly, our simulator incorporates multiscale variability that
reflects individual subject differences, allowing for a uniquely predictive tool. Experiment-
informed simulator predictions will be used to further guide ongoing experiments in SPARC
projects and to interpret patient data, allowing for tight integration and synergy across multiple
arms of the SPARC initiative. The simulator has 8 tasks. In Task 1, we model neural circuitry. In
Task 2, we incorporate into the simulator the anatomical features required for intrinsic
autonomic regulation of cardiovascular function. In Task 3, we simulate synaptic control of
vascular and cardiac myocytes. Task 4 involves modeling autonomic effects on subcellular
signaling and electrophysiology in vascular and cardiac myocytes, while Task 5 deals with
atomic-scale details of the molecular interactions in the adrenergic signaling cascade. Task 6
integrates data from the previous 5 tasks to predict autonomic effects on the cardiovascular
system. In Task 7, we develop tools (workflows) for model dissemination and use by others.
Finally, in Task 8 we incorporate into the simulator uncertainty quantification, sensitivity
analysis, and robustness tests. The proposed studies have the potential of transforming our
understanding of how cardiac and vascular function is regulated by the autonomic nervous
system and provide insights into how this neuro-cardiovascular axis could be clinically tuned
with molecular precision to improve patient outcomes.
项目摘要
1628年,威廉·哈维(William Harvey)写道:“心灵的每一种情感,无论是伴随着痛苦还是痛苦,
快乐,希望或恐惧,是一种激动的原因,其影响延伸到心脏。
尽管几个世纪以来人们都认识到大脑和心脏之间的基本联系,
对于自主神经控制在正常心脏控制中的作用,
以及危及生命的心脏事件的阵发性。预测机制
神经系统放电和由此产生的突发事件之间的相互作用的基础
心脏和血管事件将最终允许个体识别和特定靶向
心律失常的诱因条件下的药物,甚至是直接电刺激。我们提出
开发神经心血管模拟器套件来解决这个问题。拟议
模拟器是无与伦比的,因为它将整合解剖和功能数据,从
原子水平的离子通道和关键信号蛋白,以亚细胞到细胞,器官,
系统数据和模拟。重要的是,我们的模拟器采用了多尺度可变性,
反映了个体受试者的差异,允许使用独特的预测工具。实验-
模拟器的预测结果将被用来进一步指导正在进行中的、在美国宇航局进行的试验。
项目和解释患者数据,允许多个项目之间的紧密集成和协同作用,
的武器。模拟器有8个任务。在任务1中,我们对神经回路进行建模。在
任务2,我们在模拟器中加入了固有的解剖特征,
自主调节心血管功能。在任务3中,我们模拟突触控制,
血管和心肌细胞。任务4涉及对亚细胞的自主效应进行建模,
信号和电生理学,而任务5涉及
肾上腺素能信号级联中分子相互作用的原子尺度细节。任务6
整合前5项任务的数据,预测自主神经对心血管的影响
系统在任务7中,我们开发了用于模型传播和其他人使用的工具(工作流)。
最后,在任务8中,我们将不确定性量化、灵敏度
分析和鲁棒性测试。拟议的研究有可能改变我们的
了解心脏和血管功能如何由自主神经调节
系统,并提供如何在临床上调整这种神经-心血管轴的见解
用分子精确度来改善病人的治疗效果
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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{{ truncateString('COLLEEN E CLANCY', 18)}}的其他基金
Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
- 批准号:
10406687 - 财政年份:2021
- 资助金额:
$ 69.19万 - 项目类别:
Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
- 批准号:
10394236 - 财政年份:2020
- 资助金额:
$ 69.19万 - 项目类别:
Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
- 批准号:
10614418 - 财政年份:2020
- 资助金额:
$ 69.19万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10397892 - 财政年份:2018
- 资助金额:
$ 69.19万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10001997 - 财政年份:2018
- 资助金额:
$ 69.19万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10215080 - 财政年份:2018
- 资助金额:
$ 69.19万 - 项目类别:
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