Multiscale Model of Thrombosis in Artificial Circulation
Multiscale Model of Thrombosis in Artificial Circulation
批准号:
10615881
负责人:
JAMES F. ANTAKI
金额:
$68.95万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
未结题
起止时间:
2009-02-01 至 2025-04-30
关键词:
Adverse eventAmericanAnticoagulantsAnticoagulationAntithrombin IIIArtificial HeartAspirinBasic ScienceBenchmarkingBiochemical PathwayBiological AssayBloodBlood PlateletsBlood coagulationCalibrationCannulasCardiovascular systemCathetersChemistryChronicCirculationClinicalCoagulation ProcessCodeColorCommunitiesComputer SimulationConvectionDepositionDevelopmentDevicesDiffusionDimensionsDipyridamoleDoseElementsEndotheliumFibrinFreedomFutureGrowthHeart ValvesHematologyHemorrhageHeparinIncidenceInjuryLiquid substanceMainstreamingMapsMediatingMicrofluidicsModelingOrganPatientsPerformancePhasePlasmaPlatelet ActivationPredispositionPropertyReactionResourcesRiskSocietiesStrokeSurfaceTherapeutic EmbolizationThrombinThromboembolismThrombolytic TherapyThrombosisThrombusTranslationsVentricularWarfarinartificial lungblood pumpclinical translationclinically relevantclopidogrelcrosslinkdosageexperiencehealinghemodynamicsimplantable deviceimprovedinhibitorinnovationmodels and simulationmulti-scale modelingneglectprogramssimulationthromboembolic strokethrombolysisuser-friendlyventricular assist devicevirtual
中文摘要
毫不夸张地说,所有血液润湿器械都容易发生意外血栓形成,
流血-带来可怕的后果。尽管有几十年的临床经验,基础研究,
和计算流体动力学建模,实际上仍然不可能避免有害的
血液学影响,无抗凝,或实验性试错。不幸
其后果是使人衰弱的不良事件(如中风)发生率不可接受,
出血在过去的25年多里,这一持久的挑战推动了PI追求
血栓形成的确定性、多尺度、多组分、对流-扩散-反应模型
它包含了魏尔啸的三要素:血液的特性,流动的特征,
和表面化学我们在这个项目的前一阶段取得了重大进展,
现在能够在多个尺度上以惊人的准确度预测血小板沉积:
小裂缝到全尺寸的心室辅助装置。我们现在希望延长血栓形成
模型包括血栓稳定和重塑。具体目标1是扩大
模型包括纤维蛋白交联、内皮化和血管翳形成。我们假设
这些改进将提高模型的实用性,
粘附血栓,因此栓塞的风险,溶栓的影响和发展
新生内膜表面和/或血管翳生长。具体目标2将纳入生化
模拟常用的抗凝途径,大大提高其临床
翻译.具体目标3将证明增强血栓形成的性能
在一系列临床相关条件下,包括旋转式
具有浸血轴承的血泵,导管血泵,机械心脏瓣膜,
和心室插管。我们将在一系列条件下进行参数化模拟
根据血流动力学在器械内生成“血栓形成威胁水平”图
和血液学独立变量:流速、血小板反应性/计数/预活化,以及
抗凝我们还打算将该模型打包成一个用户友好的、公开可用的
应用程序,以促进传播这一资源的设计师和从业人员,
改善心血管装置最有害和最持久的并发症之一。
英文摘要
ALL blood-wetted devices, without exaggeration, are susceptible to unintended thrombosis and
bleeding – with dire consequences. In spite of decades of clinical experience, basic research,
and computational fluid dynamics modeling, it is still virtually impossible to avoid deleterious
hematological effects without anticoagulation, or experimental trail-and-error. The unfortunate
consequence is an unacceptable rate of debilitating adverse events such as stroke and
hemorrhage. This abiding challenge has driven the PIs over the past 25+ years to pursue a
deterministic, multi-scale, multi-constituent, convection-diffusion-reaction model of thrombosis
that embraces the principle elements of Virchow’s Triad: properties of blood, character of flow,
and surface chemistry. We have made significant progress in the previous phase of this project,
and now able to predict platelet deposition with remarkable accuracy at multiple scales: from
small crevices to full-sized ventricular assist devices. We now wish to extend the thrombosis
model to include thrombus stabilization, and remodeling. Specific Aim 1 will be to extend the
model to include fibrin cross-linking, endothelialization and pannus formation. We hypothesize
that these improvements will enhance the utility of the model for simulating the stability of
adherent thrombus, hence risk of embolization, the effects of thrombolysis and the development
of neointimal surface and/or pannus growth. Specific Aim 2 will be to incorporate biochemical
pathways to simulate commonly used anticoagulation, and greatly improve its clinical
translation. Specific Aim 3 will be to demonstrate the performance of the enhanced thrombosis
model with macro-scale devices over a range of clinically relevant conditions, including a rotary
blood pump with blood-immersed bearing, a catheter blood pump, a mechanical heart valve,
and a ventricular cannula. We will perform simulations parametrically, over a range of conditions
to produce a map of “Thrombosis Threat Level” within the device as a function of hemodynamic
and hematological independent variables: flow rate, platelet reactivity/count/pre-activation, and
anticoagulation. We further intend to package the model in a user-friendly, publicly available
application to promote dissemination of this resource for both designers and practitioners to
ameliorate one of the most pernicious and abiding complications of cardiovascular devices.
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A Continuum Model for the Unfolding of von Willebrand Factor.
冯维勒布兰德因子展开的连续体模型。
DOI:
10.1007/s10439-021-02845-5
发表时间:
2021-09
期刊:
ANNALS OF BIOMEDICAL ENGINEERING
影响因子:
3.8
作者:
[Zhussupbekov, Mansur, Mendez Rojano, Rodrigo, Wu, Wei-Tao, Massoudi, Mehrdad, Antaki, James F.]
通讯作者:
Antaki, James F.
DOI:
10.1097/mat.0000000000001841
发表时间:
2023-04-01
期刊:
ASAIO JOURNAL
影响因子:
4.2
作者:
[Kang, Junhyuk, Jayaraman, Anjana, Antaki, James F., Kirby, Brian J.]
通讯作者:
Kirby, Brian J.
DOI:
10.1002/jbm.a.35202
发表时间:
2015-04
期刊:
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
影响因子:
4.9
作者:
[Jamiolkowski, Megan A., Woolley, Joshua R., Kameneva, Marina V., Antaki, James F., Wagner, William R.]
通讯作者:
Wagner, William R.
Exploratory Simulation of Thrombosis in a Temporary LVAD Catheter Pump within a Virtual In-vivo Left Heart Environment.
在虚拟体内左心环境中临时 LVAD 导管泵中血栓形成的探索性模拟。
DOI:
--
发表时间:
2023
期刊:
ArXiv
影响因子:
--
作者:
[Burgreen,GregW, Zhussupbekov,Mansur, Rojano,RodrigoMéndez, Antaki,JamesF]
通讯作者:
Antaki,JamesF
The importance of dQ/dt on the flow field in a turbodynamic pump with pulsatile flow.
dQ/dt 对脉动流涡轮动力泵流场的重要性。
DOI:
10.1111/j.1525-1594.2009.00849.x
发表时间:
2009
期刊:
Artificial organs
影响因子:
2.4
作者:
[Shu,Fangjun, Vandenberghe,Stijn, Antaki,JamesF]
通讯作者:
Antaki,JamesF
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