Compliant Thoracic Artificial Lungs

顺应性胸腔人工肺

• 批准号: 8197545
• 负责人: Keith E Cook
• 金额: $ 35.69万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197545
• 关键词: Acute; Animal Model; Animals; Benchmarking; Blood Circulation; Blood flow; Carbon Dioxide; Cardiac Output; Chest; Chronic; Chronic lung disease; Coagulation Process; Data; Development; Device Designs; Devices; Disease model; Distal; Ensure; Exercise; Extracorporeal Membrane Oxygenation; Filtration; Functional disorder; Gases; Goals; Health; Heart; Housing; In Vitro; Inflammation; Left atrial structure; Liquid substance; Long-Term Effects; Lung; Lung Transplantation; Lung diseases; Mechanical ventilation; Mechanics; Metabolic; Methods; Modeling; Organ; Outcome; Output; Patients; Performance; Physiology; Pulmonary Artery Branch; Pulmonary Hypertension; Pulmonary Vascular Resistance; Pulmonary artery structure; Pulsatile Flow; Pump; Resistance; Right Ventricular Function; Right ventricular structure; Sheep; Simulate; Staging; Structure; System; Testing; Time; Transplant Recipients; Transplantation; Ventricular; Work; artificial lung; base; design; electric impedance; engineering design; hemodynamics; improved; in vitro testing; in vivo; meetings; prototype; research clinical testing; respiratory

DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to develop compliant, thoracic artificial lungs (cTALs) that can be used as a bridge to transplant for patients with end-stage respiratory disease. As a bridge to lung transplantation, a cTAL would allow for more patients to be transplanted and improve outcomes. Blood flow to the cTAL comes from the pulmonary artery (PA), driven by the right ventricle. Blood flow returns to the distal PA or branch of the PA (PA-PA attachment) or the left atrium (PA-LA attachment). These devices are designed to supply a patient's full gas transfer requirements with significantly less coagulation and inflammation than with extracorporeal membrane oxygenation (ECMO). Our group's previous work has led to devices that met these goals in large animals. However, this work also indicates that the fluid mechanical impedance of these devices can cause a significant reduction in cardiac output (CO) when attached in the PA- PA configuration. If not for this reduction in CO, PA-PA attachment would be the ideal means of attaching cTALs, as it allows the natural lung to maintain its normal filtration and metabolic functions. The cause of the reduction in CO is due, in large part, to excessive cTAL impedance. The studies in this proposal are aimed at designing a cTAL with very low impedance such that it can be used in any attachment configuration with little to no reduction in CO. This design should also allow for increases in CO with exercise. Five studies are proposed to meet this goal. (1) The relationship between pulmonary system impedance and CO will be determined using an intact heart, large animal model. The developed relationship will be used to set impedance benchmarks for the design of an improved cTAL that causes little to no reduction in CO during PA-PA attachment. (2) Fluid structure interaction (FSI) modeling will be used to design a cTAL that meets the impedance benchmarks. Preliminary FSI and in-vitro data indicates that cTAL impedance can be reduced to at least 33-50% of current thoracic artificial lungs. This should result in large improvements in CO during cTAL use. (3) The selected design will be tested in-vitro under pulsatile flow to confirm hemodynamic performance. (4) The cTAL will be tested in-vivo to determine short term (< 8 hrs) gas exchange and hemodynamic performance in the PA-PA and PA-LA configurations at normal and elevated CO. Lastly, (5) the cTAL will be tested in-vivo over 14 days to assess device performance and animal physiology. All animal studies will utilize a model of pulmonary hypertension during chronic lung disease. The resulting device will be ready for pre- clinical testing. PUBLIC HEALTH RELEVANCE: The goal of this project is to design and test compliant artificial lungs. These devices will give chronic lung disease patients more time to find a donor lung and improve their health before and after transplantation.

描述（由申请人提供）：该提案的长期目标是开发合规性的胸部人造肺（CTALS），这些肺（CTAL）可用作终末期呼吸道疾病患者移植的桥梁。作为进行肺移植的桥梁，CTAL将允许更多患者接受移植并改善预后。流向CTAL的血流来自右心室驱动的肺动脉（PA）。血流返回到PA（PA-PA附件）或左心房（PA-LA附件）的远端PA或分支。与体外膜氧合（ECMO）相比，这些设备旨在提供患者的完整气体转移需求，其凝结和炎症明显少得多。我们小组以前的工作导致了在大型动物中实现这些目标的设备。但是，这项工作还表明，当在Pa-pa配置中附着时，这些设备的流体机械阻抗会导致心脏输出（CO）显着降低。如果不是为了减少CO，PA-PA附件将是附着CTAL的理想手段，因为它允许天然肺保持其正常的过滤和代谢功能。 CO减少的原因在很大程度上是由于过度的CTAL阻抗。该提案中的研究旨在设计具有非常低阻抗的CTAL，以便可以在CO的任何附件配置中使用。该设计还应通过运动来增加CO的增加。提出了五项研究以实现这一目标。 （1）使用完整的心脏，大动物模型确定肺系统阻抗与CO之间的关系。开发的关系将用于设定阻抗基准，以设计改进的CTAL，这在PA-PA附件期间几乎不会减少CO。 （2）流体结构相互作用（FSI）建模将用于设计符合阻抗基准的CTAL。初步的FSI和维特罗数据表明，可以将CTAL阻抗降低至至少33-50％的当前胸部人造肺。这应该导致CTAL使用过程中的CO大大改善。 （3）选定的设计将在脉冲流下进行体外测试，以确认血液动力学性能。 （4）CTAL将在体内进行测试，以确定正常和升高CO的PA-PA和PA-LA构型中的短期（<8小时）气体交换和血液动力学性能。所有动物研究将在慢性肺部疾病期间使用肺动脉高压模型。所得设备将准备好进行临床测试。公共卫生相关性：该项目的目的是设计和测试合规性人工肺。这些设备将使慢性肺病患者有更多时间在移植前后，以找到供体肺并改善其健康状况。