Integration of Compliance Chambers into Diaphragm Displacement Pump to Double the Pumping Flow of Pediatric Paracorporeal Pulsatile Ventricular Assist Device

将顺应室集成到隔膜排量泵中，使儿科体外脉动心室辅助装置的泵流量加倍

• 批准号: 10761399
• 负责人: Stephen R Topaz
• 金额: $ 29.59万
• 依托单位: W-Z BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761399
• 关键词: Adult; Aorta; Apical; Berlin; Biotechnology; Blood; Blood flow; Cannulas; Cardiac; Cardiogenic Shock; Cardiomyopathies; Child; Childhood; Complex; Coupled; Data; Devices; Diastole; Drainage procedure; Engineering; FDA approved; Frequencies; Glycerol; Goals; Head; Heart; Heart Transplantation; Heart failure; Housing; Implant; Infusion procedures; Interruption; Kentucky; Laboratory Animal Production and Facilities; Lung; Membrane; Molds; Motor; Movement; Myocarditis; Patients; Performance; Phase; Polyurethanes; Publications; Pulsatile Flow; Pump; Research Support; Respiratory Diaphragm; Scientist; Silicones; Small Business Innovation Research Grant; Stress; Surgeon; System; Systole; Technology; Testing; Thrombosis; Time; Trauma; Tricuspid valve structure; Universities; Vacuum; Weight; Withdrawal; biomaterial compatibility; blood damage; blood pump; commercialization; congenital heart disorder; design; experience; fabrication; flexibility; hemocompatibility; improved; improved outcome; in vivo; innovation; invention; left ventricular assist device; light weight; minimally invasive; multidisciplinary; neonate; novel; pediatric heart failure; pediatric patients; polycarbonate; pressure; prototype; research and development; shear stress; ventricular assist device

The paracorporeal Berlin Heart EXCOR is the only FDA-approved ventricular assist device (VAD) for pediatric patients. This pulsatile diaphragm displacement pump (DDP) is small/light weight to facilitate pediatric patient ambulation. However, EXCOR efficiency is only 50% since it withdraws and pumps blood at different times (interrupted pulsatile flow). This generates a high peak blood flow rate, which may cause blood damage. A paracorporeal continuous flow PediMag VAD has also been used in smaller children. This centrifugal pump is highly efficient due to the constant flow through the drainage/infusion cannulas, but the PediMag pump head must be attached to a bulky/heavy motor, which hinders ambulation. We previously developed a transapical to aorta (TAA) double lumen cannula (DLC) for a minimally invasive ambulatory LVAD, which showed excellent 96 hr performance/hemocompatibility in neonate lambs. Our ultimate goal is to develop an efficient, minimally invasive, paracorporeal LVAD system for pediatric patients, which combines the small size/weight (ambulation potential) of current interrupted pulsatile flow pump (e.g EXCOR) and the current high efficiency of a continuous flow pump (e.g PediMag). The enabling technology is a compliant diaphragm displacement pump (cDDP), which has compliance chambers integrated into the drainage and infusion outlets to double blood flow. The cDDP will be high performing due to: 1) noninterrupted/continuous blood flow; 2) infusion/drainage compliance chambers that decrease cDDP afterload/increase cDDP preload. The lower peak drainage/infusion flow of the cDDP will also reduce blood trauma. Preliminary data showed that adding compliance chambers increased pumping flow from 1.1 to 2.6 L/min and decreased peak flow rate. The Phase I SBIR objective is to design and fabricate a cDDP working prototype with optimal compliance chambers size. This cDDP will be tested in lambs with our previously developed TAA DLC. Specific Aim 1: To design, fabricate, and bench test a cDDP. Compliance chambers will be integrated into the cDDP drainage and infusion outlets. The cDDP will be made of polycarbonate housing with a polyurethane diaphragm in the middle. A tricuspid valve will connect the cDDP housing to the two small silicone compliance chambers. The final prototype will be tested for 1 week in a 37% glycerin mock loop for performance/reliability/durability. Specific Aim 2: To test the cDDP working prototype in lambs. The cDDP will be combined with the TAA DLC to form a less invasive, ambulatory LVAD, which will be tested in 10-15 kg lambs (n=9) to evaluate 6 hr performance/reliability and initial biocompatibility. Prototype design/fabrication/bench testing will be done at W-Z Biotech, and the lamb studies will be done at the University of Kentucky. Rather than fine-tuning existing technology, our cDDP is a novel invention, which will enable a pulsatile paracorporeal VAD with doubled efficiency. This technology can also be used in adults and may significantly impact cardiogenic shock/bridge to heart transplant management.

体外柏林心脏 EXCOR 是 FDA 唯一批准的心室辅助装置 (VAD) 儿科患者。这款脉动隔膜排量泵 (DDP) 体积小/重量轻，方便儿科使用 病人下床活动。然而，EXCOR 的效率只有 50%，因为它在不同的时间抽血和泵血。 次（脉动流中断）。这会产生很高的峰值血流量，可能会导致血液损伤。 体外连续流动 PediMag VAD 也已用于较​​小的儿童。这种离心泵 由于通过引流/输液插管的流量恒定，效率很高，但 PediMag 泵头 必须连接到笨重的电机上，这会妨碍移动。我们之前开发了一种经心尖 主动脉 (TAA) 双腔插管 (DLC) 用于微创动态 LVAD，显示出优异的性能 新生羔羊的 96 小时性能/血液相容性。我们的最终目标是开发一个高效、最小化的 适用于儿科患者的侵入性体外 LVAD 系统，该系统结合了小尺寸/重量（步行 电流中断脉动流泵（例如 EXCOR）的潜力）和电流高效率 连续流泵（例如 PediMag）。支持技术是合规隔膜活塞泵 （cDDP），其将顺应室集成到引流和输液出口中以使血流量加倍。 cDDP 具有高性能，因为：1) 不间断/连续的血流； 2）输液/引流 降低 cDDP 后负荷/增加 cDDP 预负荷的顺应室。引流/输注峰值较低 cDDP 的流动也将减少血液创伤。初步数据表明，添加顺应室 将泵送流量从 1.1 L/min 增加至 2.6 L/min，并降低峰值流量。第一阶段 SBIR 的目标是 设计和制造具有最佳顺应室尺寸的 CDDP 工作原型。该 CDDP 将 使用我们之前开发的 TAA DLC 在羔羊身上进行了测试。具体目标 1：设计、制造和试验 测试 CDDP。顺应室将集成到 cDDP 引流和输液出口中。顺铂 将由聚碳酸酯外壳制成，中间有聚氨酯隔膜。三尖瓣将 将 cDDP 外壳连接到两个小型硅胶顺应室。最终原型将进行测试 在 37% 甘油模拟循环中运行 1 周，以确保性能/可靠性/耐用性。具体目标 2：测试 cDDP 羔羊的工作原型。 cDDP 将与 TAA DLC 相结合，形成侵入性较小的、 动态 LVAD，将在 10-15 公斤羔羊 (n=9) 中进行测试，以评估 6 小时的性能/可靠性和 初始生物相容性。原型设计/制造/台架测试将在 W-Z Biotech 完成，羔羊 研究将在肯塔基大学进行。我们的 cDDP 不是对现有技术进行微调，而是 新颖的发明，将使脉动体外 VAD 的效率加倍。这项技术可以 也可用于成人，可能会显着影响心源性休克/心脏移植管理的桥梁。