Multiscale Model of Thrombosis in Artificial Circulation

人工循环血栓形成的多尺度模型

• 批准号: 10615881
• 负责人: JAMES F. ANTAKI
• 金额: $ 68.95万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615881
• 关键词: Adverse event; American; Anticoagulants; Anticoagulation; Antithrombin III; Artificial Heart; Aspirin; Basic Science; Benchmarking; Biochemical Pathway; Biological Assay; Blood; Blood Platelets; Blood coagulation; Calibration; Cannulas; Cardiovascular system; Catheters; Chemistry; Chronic; Circulation; Clinical; Coagulation Process; Code; Color; Communities; Computer Simulation; Convection; Deposition; Development; Devices; Diffusion; Dimensions; Dipyridamole; Dose; Elements; Endothelium; Fibrin; Freedom; Future; Growth; Heart Valves; Hematology; Hemorrhage; Heparin; Incidence; Injury; Liquid substance; Mainstreaming; Maps; Mediating; Microfluidics; Modeling; Organ; Patients; Performance; Phase; Plasma; Platelet Activation; Predisposition; Property; Reaction; Resources; Risk; Societies; Stroke; Surface; Therapeutic Embolization; Thrombin; Thromboembolism; Thrombolytic Therapy; Thrombosis; Thrombus; Translations; Ventricular; Warfarin; artificial lung; blood pump; clinical translation; clinically relevant; clopidogrel; crosslink; dosage; experience; healing; hemodynamics; implantable device; improved; inhibitor; innovation; models and simulation; multi-scale modeling; neglect; programs; simulation; thromboembolic stroke; thrombolysis; user-friendly; ventricular assist device; virtual

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.

毫不夸张地说，所有的湿血装置都容易产生意外血栓和

项目成果

Extracting Mural and Volumetric Growth Patterns of Platelet Aggregates on Engineered Surfaces by Use of an Entity Tracking Algorithm.

• 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.

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.

Real time visualization and characterization of platelet deposition under flow onto clinically relevant opaque surfaces.

• 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。

• 发表时间: 2023
• 期刊: ArXiv
• 作者: Burgreen,GregW;Zhussupbekov,Mansur;Rojano,RodrigoMéndez;Antaki,JamesF
• 通讯作者: Antaki,JamesF

Preclinical performance of a pediatric mechanical circulatory support device: The PediaFlow ventricular assist device.

儿科机械循环支持装置的临床前性能：PediaFlow 心室辅助装置。

• DOI: 10.1016/j.jtcvs.2018.04.062
• 发表时间: 2018
• 期刊: The Journal of thoracic and cardiovascular surgery
• 作者: Olia,SalimE;Wearden,PeterD;Maul,TimothyM;Shankarraman,Venkat;Kocyildirim,Ergin;Snyder,ShaunT;Callahan,PatrickM;Kameneva,MarinaV;Wagner,WilliamR;Borovetz,HarveyS;Antaki,JamesF
• 通讯作者: Antaki,JamesF