Development of a TransApical to Aorta Double Lumen Cannula for a Neonate LVAD

用于新生儿 LVAD 的经心尖至主动脉双腔插管的开发

• 批准号: 9555884
• 负责人: Stephen R Topaz
• 金额: $ 71.48万
• 依托单位: W-Z BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9555884
• 关键词: Acute; Adult; Animals; Aorta; Apical; Berlin; Biotechnology; Blood; Blood Circulation; Blood Transfusion; Body Weight; Cannulas; Cannulations; Carbon Dioxide; Cardiac; Cardiac Surgery procedures; Cardiogenic Shock; Cardiomyopathies; Cardiopulmonary Bypass; Chest; Chest wall structure; Childhood; Clinical; Complex; Coronary artery; Coupled; Development; Devices; Eating; Engineering; Ensure; Enteral Nutrition; Excision; FDA approved; Food; Future; Gases; Glycerol; Goals; Grant; Heart; Heart Diseases; Heart Transplantation; Heart failure; Hemoglobin; Hemolysis; Hemorrhage; Hour; Implant; Incidence; Infection; Infusion procedures; Kentucky; Laboratory Animal Production and Facilities; Left; Liquid substance; Lung; Mediastinal; Milk; Morbidity - disease rate; Neonatal; Newborn Infant; Obstruction; Operative Surgical Procedures; Patients; Pediatrics; Performance; Phase; Platelet Count measurement; Polyurethanes; Positioning Attribute; Publications; Recovery; Research Support; Safety; Savings; Scientist; Secure; Sedation procedure; Site; Small Business Innovation Research Grant; Solid; Sternotomy; Surgeon; System; Technology; Testing; Thoracotomy; Transplantation; Universities; Ventricular; Weaning; Weight; aortic valve; artificial lung; base; biomaterial compatibility; blood pump; congenital heart disorder; design; experience; falls; feeding; implantation; in vivo; left ventricular assist device; mortality; multidisciplinary; neonate; novel; pediatric patients; performance tests; phase 1 study; prototype; research and development; respiratory

Left ventricular assist device (LVAD) support allows the neonate with congenital heart disease or cardiomyopathy to grow to a larger body weight that is more feasible for complex surgical correction or heart transplant. The Berlin Heart ExCOR, is FDA-approved for pediatric LVAD application. Although this device is outside the body, the outflow graft may still create coronary artery/heart compression. Our ultimate goal is to develop a less invasive and dependable LVAD system for the neonate as well as older pediatric patients. The enabling technology is a double lumen cannula (DLC), which is inserted from the apex into the aorta. Coupled with an existing blood pump, this DLC withdraws blood from the LV and delivers blood into the aorta, unloading the LV. Our DLC-based LVAD only requires a one site, less invasive apex cannulation. The advantages are: 1) no outflow graft and associated heart/coronary artery compression; 2) no need of cardiopulmonary bypass and associated blood transfusion; 3) reserves more invasive sternotomy for future complex heart surgery. This transapical to aorta (TAA) DLC enables a high performance paracorporeal/ extracorporeal LVAD and allows addition of a gas exchanger for cyanotic heart disease. Our Phase I study proved that the TAA DLC-based neonate LVAD system was very easy to implant via a small left thoracotomy and efficiently unloaded the LV for 6 hours with no increase in free hemoglobin and no decrease in hemoglobin and platelet counts. Phase II SBIR objective: Based on the Phase I results, we will optimize the design and fabricate a final commercial quality TAA DLC prototype for even smaller neonate application and for 5 day survival lamb studies. Specific Aim 1: To design, fabricate, and bench-test the high efficiency, commercial quality TAA DLC prototype for smaller neonate application and for 5 day survival in vivo lamb studies. The TAA DLC will be made of one piece reinforced polyurethane. Computational fluid dynamics will be used to optimize the DLC design. A DLC anchoring system will be also developed to secure TAA DLC on apex and chest wall for long-term ambulatory use. A 13 Fr/10 Fr TAA DLC will be developed for 2-4 kg neonate lamb acute study and a 19 Fr/15 Fr TAA DLC will developed for 4 week old lamb (20 kg) survival study. The final prototype will be tested for performance, reliability, and hemolysis. Thirty day durability will be tested in 37% glycerin. Specific Aim 2: To test new 13/10 Fr TAA DLC-based LVAD in 2- 4 kg neonate lamb (n=5). This 6 hour study is designed to prove TAA DLC suitable for clinical neonate LVAD application. We will investigate ease of TAA deployment and in vivo performance, as well as potential aortic valve obstruction by extension infusion cannula. Specific Aim 3: To test the TAA DLC prototype for 5 days LVAD application in 4 weeks old neonate lamb (n=5). The 4 week old lamb is still considered a neonate but almost fully weaned, allowing us to perform 5 day survival study. This in vivo study will test performance, reliability, durability, and biocompatibility. Upon this SBIR grant completion, the commercialized TAA DLC will provide a less invasive neonate LVAD.

左心室辅助装置 (LVAD) 支持允许患有先天性心脏病或患有先天性心脏病的新生儿 心肌病发展到更大的体重，更适合复杂的手术矫正或心脏 移植。 Berlin Heart ExCOR 已获得 FDA 批准用于儿科 LVAD 应用。虽然这个装置是 在体外，流出移植物仍可能产生冠状动脉/心脏压迫。我们的最终目标是 为新生儿和老年儿科患者开发侵入性较小且可靠的 LVAD 系统。这 支持技术是双腔插管（DLC），从心尖插入主动脉。耦合 使用现有的血泵，该 DLC 从左心室抽取血液并将血液输送到主动脉，从而卸载 LV。我们基于 DLC 的 LVAD 只需要一个部位、侵入性较小的心尖插管。优点是： 1) 无流出移植物和相关的心脏/冠状动脉受压； 2）无需体外循环 以及相关的输血； 3）为未来复杂的心脏手术预留更具侵入性的胸骨切开术。这 经心尖至主动脉 (TAA) DLC 可实现高性能体外/体外 LVAD，并允许 添加用于紫绀性心脏病的气体交换器。我们的第一阶段研究证明，基于 TAA DLC 的 新生儿 LVAD 系统非常容易通过小型左胸切开术植入，并有效地卸载 LV 6小时，游离血红蛋白没有增加，血红蛋白和血小板计数没有减少。第二阶段 SBIR目标：根据第一阶段的结果，我们将优化设计并制造最终的商业产品 优质 TAA DLC 原型，适用于更小的新生儿应用和 5 天存活羔羊研究。具体的 目标 1：设计、制造和测试高效率、商业品质的 TAA DLC 原型 适用于较小的新生儿应用和羔羊体内 5 天存活率研究。 TAA DLC 将由 一件式增强聚氨酯。计算流体动力学将用于优化 DLC 设计。一个 还将开发 DLC 锚定系统，以将 TAA DLC 长期固定在心尖和胸壁上 流动使用。将开发 13 Fr/10 Fr TAA DLC 用于 2-4 kg 新生羔羊急性研究和 19 Fr/15 Fr TAA DLC 将为 4 周龄羔羊（20 公斤）生存研究而开发。最终原型将进行测试 性能、可靠性和溶血。将在 37% 甘油中测试三十天的耐久性。具体目标 2： 在 2-4 kg 新生羔羊中测试新的基于 13/10 Fr TAA DLC 的 LVAD (n=5)。这个 6 小时的学习旨在 证明TAA DLC适合临床新生儿LVAD应用。我们将研究 TAA 部署的难易程度 和体内性能，以及通过延长输注插管潜在的主动脉瓣阻塞。具体的 目标 3：测试 TAA DLC 原型在 4 周大的新生羔羊 (n=5) 中应用 5 天的 LVAD。 4 周大的羔羊仍然被认为是新生儿，但几乎完全断奶，让我们可以进行 5 天的表演 生存研究。这项体内研究将测试性能、可靠性、耐用性和生物相容性。在此基础上 SBIR 拨款完成后，商业化的 TAA DLC 将提供侵入性较小的新生儿 LVAD。