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.

旁心柏林心脏EXCOR是FDA批准的唯一心室辅助装置（VAD）， 儿科患者。该脉动隔膜置换泵（DDP）体积小/重量轻， 病人救护车。然而，EXCOR效率仅为50%，因为它以不同的速度抽取和泵送血液， 次（间断搏动流）。这会产生高峰血液流速，可能导致血液损伤。 一个paracentral连续流PediMag VAD也已用于较小的儿童。该离心泵 由于通过引流/输注套管的恒定流量，因此具有高效率，但PediMag泵头 必须连接到一个笨重的/沉重的电机，这阻碍了Amplitude。我们以前开发了一种经心尖， 主动脉（TAA）双腔插管（DLC）用于微创非卧床LVAD，表现出色 新生羔羊96小时性能/血液相容性。我们的最终目标是开发一种高效、最低限度的 用于儿科患者的有创、并行LVAD系统，该系统结合了小尺寸/重量（amplitude） 当前中断的脉动流泵（例如EXCOR）的效率和当前高效率的 连续流泵（例如PediMag）。使能技术是一个顺应隔膜排量泵 （cDDP），其具有整合到引流和输注出口中的顺应性腔室，以使血流加倍。 cDDP将具有高性能，因为：1）无中断/连续血流; 2）输注/引流 降低cDDP后负荷/增加cDDP前负荷的顺应性腔室。引流/输注峰值较低 cDDP的流动也将减少血液创伤。初步数据显示，增加合规室 将泵送流量从1.1 L/min增加到2.6 L/min，并降低峰值流速。第一阶段SBIR的目标是 设计并制作了具有最佳顺应腔尺寸的cDDP工作原型。该cDDP将是 用我们以前开发的TAA DLC在羔羊中进行了测试。具体目标1：设计、制造和调试 测试cDDP。顺应性腔室将集成到cDDP引流和输注出口中。cDDP 将由聚碳酸酯外壳制成，中间带有聚氨酯隔膜。三尖瓣 将cDDP外壳连接到两个小型硅胶顺应性腔室。最终的原型将进行测试， 在37%甘油模拟环中使用1周，以提高性能/可靠性/耐用性。具体目标2：检测cDDP 在羊羔身上做原型cDDP将与TAA DLC结合，形成一种侵入性较小的， 非卧床LVAD，将在10-15 kg羔羊（n=9）中进行试验，以评价6小时性能/可靠性， 初始生物相容性。原型设计/制造/台架测试将在W-Z Biotech完成， 研究将在肯塔基州大学进行。我们的cDDP不是对现有技术进行微调， 本发明是一种新颖的发明，它将使脉动式旁路VAD具有加倍的效率。这项技术可以 也可用于成人，并可能显著影响心源性休克/心脏移植管理的过渡。