Multiscale Model of Thrombosis in Artificial Circulation

人工循环血栓形成的多尺度模型

• 批准号: 10317925
• 负责人: JAMES F. ANTAKI
• 金额: $ 71.87万
• 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/10317925
• 关键词: Adverse event; American; Anticoagulants; Anticoagulation; Antithrombin III; Artificial Heart; Aspirin; Basic Science; Benchmarking; Biochemical Pathway; Biological Assay; Blood; Blood Circulation; Blood Platelets; Blood coagulation; Cannulas; Cardiovascular system; Catheters; Chemistry; Chronic; Clinical; Coagulation Process; Code; Color; Communities; Computer Simulation; Convection; Deposition; Development; Devices; Diffusion; 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; Property; Reaction; Resources; Risk; Societies; Stroke; Surface; Therapeutic Embolization; Thrombin; Thromboembolism; Thrombolytic Therapy; Thrombosis; Thrombus; Transact; Translations; Triad Acrylic Resin; Ventricular; Warfarin; artificial lung; blood pump; clinical translation; clinically relevant; clopidogrel; crosslink; dosage; experience; healing; hemodynamics; implantable device; improved; inhibitor/antagonist; 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，所有沾有血液的装置都容易发生意外血栓形成和 出血——造成可怕的后果，尽管有数十年的临床经验和基础研究， 和计算流体动力学建模，实际上仍然不可能避免有害的 不幸的是，没有抗凝或实验反复试验的血液学影响。 其后果是令人无法接受的使人衰弱的不良事件，如中风和 这种持续不断的挑战促使 PI 在过去 25 年多的时间里不断追求 血栓形成的确定性、多尺度、多成分、对流扩散反应模型 它包含了魏尔啸三联征的基本要素：血液的特性、流动的特征、 我们在该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极高的准确性预测血小板沉积： 我们现在希望扩大血栓形成。 模型包括血栓稳定和重塑，具体目标 1 将是延长 模型包括纤维蛋白交联、内皮化和血管翳形成。 这些改进将增强模型模拟稳定性的实用性 粘附血栓，因此存在栓塞的风险、溶栓的影响和发展 新内膜表面和/或血管翳生长的具体目标2将是结合生化。 模拟常用抗凝途径，极大提高其临床效果 具体目标 3 将是证明增强血栓形成的性能。 在一系列临床相关条件下使用宏观设备的模型，包括旋转 带浸血轴承的血泵、导管血泵、机械心脏瓣膜、 我们将在一系列条件下进行参数模拟。 根据血流动力学生成设备内“血栓形成威胁水平”图 和血液学自变量：流速、血小板反应性/计数/预激活，以及 我们打算进一步将该模型封装成用户友好的、公开可用的。 应用程序以促进设计师和从业者传播该资源 改善心血管装置最有害和最持久的并发症之一。