Development of a Minimally Invasive Single Cannulation, Compact Single Port Pulsatile Ventricular Assist Device (sppVAD) for Total LV Support

开发用于全面左心室支持的微创单插管、紧凑型单端口脉动心室辅助装置 (sppVAD)

• 批准号: 10259308
• 负责人: Stephen R Topaz
• 金额: $ 22.5万
• 依托单位: W-Z BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259308
• 关键词: Alloys; Animals; Aorta; Apical; Biotechnology; Blood; Blood Circulation; Cannulas; Cannulations; Carbon Dioxide; Cardiac; Cardiac Output; Cardiogenic Shock; Clinical; Complex; Counterpulsation; Data; Development; Devices; Engineering; Excision; Extracorporeal Membrane Oxygenation; Goals; Heart; Heart Transplantation; Hour; Housing; Kentucky; Laboratory Animal Production and Facilities; Left; Left ventricular structure; Low Cardiac Output; Lung; Mechanics; Membrane; Memory; Multiple Organ Failure; Myocardial Infarction; Organ; Pathway interactions; Patients; Performance; Perfusion; Phase; Polyurethanes; Publications; Pump; Recovery; Research; Resistance; Respiratory Diaphragm; Safety; Scientist; Self-Help Devices; Small Business Innovation Research Grant; Stress; Stroke; Surgeon; System; Techniques; Technology; Testing; Thinness; Thoracic Surgical Procedures; Thoracotomy; Universities; Withdrawal; Work; artificial lung; ascending aorta; blood pump; design; experience; flexibility; hypoperfusion; implantation; improved outcome; in vitro testing; in vivo; innovation; invention; minimally invasive; mortality; multidisciplinary; myocardial injury; novel; prevent; prototype; research and development; sheep model; simulation; ventricular assist device

Cardiogenic shock (CS) is a serious condition of reduced cardiac output (CO) with a mortality as high as 40-50%. In severe CS, end organ hypoperfusion from low CO causes multi-organ failure and elevated left ventricle (LV) preload increases LV wall stress. For severe CS, venoarterial extracorporeal membrane oxygenation is most often used and is fastest way to reestablish circulation, but it fails to unload LV in > 50% of these patients. Percutaneous mechanical circulatory support (MCS) devices are used in severe CS but may not fully stabilize circulation. Non-percutaneous MCS devices supply total cardiac support but require open chest surgery for installation. Our goal is to develop a compact, single port, pulsatile ventricular assist device (sppVAD) for total LV support that employs a minimally invasive single cannulation technique for implantation. Compared to a continuous flow LVAD, our sppVAD system may further unload the LV when synchronized with the native heart for counterpulsation. Our enabling technologies that form the sppVAD system are a valved single lumen cannula (VSLC) and a valveless single port diaphragm displacement pump (spDDP). Our innovative sppVAD system features: 1) Minimally invasive trans-apical to aorta installation by one VSLC cannulation through small left thoracotomy; 2) Smaller spDDP without inlet/outlet valves and large dead space; 3) Lower blood resistance due to shorter pathway through LV via the VSLC that serves as both inlet and outlet cannula; 4) Dependable total LV unloading; 5) Potential LV internal/stroke work decrease with counterpulsation pumping. W-Z Biotech made an initial prototype of sppVAD system, which had 3.1 L/min pumping flow against 80 mm Hg afterload in mock loop testing. Our objective in this Phase I SBIR is to develop/fabricate new working prototype of sppVAD system (VSLC and spDDP) and to test sppVAD system prototype in mock loop and severe CS sheep model. Specific Aim 1: To develop/fabricate/bench test new working prototype of sppVAD system (VSLC and spDDP). The 22 Fr VSLC main body will be memory alloy wire reinforced polyurethane (PU). Two one-way inlet valves on VSLC wall will be in LV for blood withdrawal. Two one-way outlet valves on VSLC wall near tip and a one-way outlet valve on VSLC tip will be in ascending aorta for blood delivery. The spDDP will have rigid PU housing, a soft, flexible PU diaphragm membrane, and a 50 mL pump volume. Only one 3/8” blood port will be made on spDDP for direct connection to VSLC. This sppVAD system will be tested in a bench mock loop. Specific Aim 2: To test sppVAD system prototype in a severe CS sheep model. Our severe CS sheep model will be used to test our sppVAD system prototype for ease of insertion/deployment, LV unloading performance, counterpulsation capacity, and 6 hr reliability (n=5). The sppVAD system prototype design/fabrication/in vitro testing will be done at W-Z Biotech while the in vivo animal studies will be done at University of Kentucky. Upon project completion, the commercialized sppVAD system will provide total LV support to severe CS patients via only a minimally invasive single cannulation.

心源性休克（CS）是降低心脏输出（CO）的严重状况，死亡率高至 40-50％。在严重的CS中，低CO的最终器官灌注会导致多器官故障，左升高 通风（LV）预紧力增加LV壁应力。对于严重的CS，静脉外膜外膜 充氧是最常使用的，并且是重新循环的最快方法，但无法在> 50％中卸载LV 这些患者。经皮机械电路支撑（MCS）设备用于严重CS，但可能 未完全稳定的圆圈。非经常MCS设备提供全部心脏支持，但需要开放 胸部手术进行安装。我们的目标是开发紧凑的，单端口，脉动心室辅助装置 （SPPVAD）总LV支持，员工是一种侵入性的单套管技术，用于植入。 与连续的流量LVAD相比，我们的SPPVAD系统可能会在与 本地的心脏反抗。我们构成SPPVAD系统的能力技术是一个阀门 单腔套管（VSLC）和阀单端口膜片位移泵（SPDDP）。我们的 创新的SPPVAD系统特征：1）一个VSLC的微创跨性主动脉安装 通过小左胸切开插管； 2）较小的SPDDP，没有入口/出口阀和较大的死空间； 3）由于较短的途径通过LV通过VSLC较短的血液耐药性，该途径既可以用作入口又出口 套管4）可靠的总LV卸载； 5）潜在的LV内部/中风工作随着反抗而减小 抽水。 W-Z Biotech制作了SPPVAD系统的初始原型，该原型具有3.1 l/min的抽水流量 在模拟环测试中进行80 mm HG后负载。我们在这个阶段的目标是开发/制造新的 SPPVAD系统（VSLC和SPDDP）的工作原型，并在模拟循环中测试SPPVAD系统原型 和严重的CS绵羊模型。特定目的1：开发/制造/台式测试新的工作原型 SPPVAD系统（VSLC和SPDDP）。 22 FR VSLC主体将是内存合金线加固 聚氨酯（PU）。 VSLC壁上的两个单向入口阀将在LV中进行抽血。两个单向 尖端附近VSLC墙上的出口阀和VSLC尖端上的单向出口阀将升高为血液 送货。 SPDDP将具有刚性PU外壳，柔软，柔性的PU隔膜膜和50毫升泵 体积。 SPDDP将只有一个3/8英寸的血液端口直接连接到VSLC。此SPPVAD系统 将在基准模拟循环中进行测试。特定目标2：测试严重CS中的SPPVAD系统原型 绵羊模型。我们严重的CS绵羊模型将用于测试我们的SPPVAD系统原型，以便于 插入/部署，LV卸载性能，抗管能力和6个小时的可靠性（n = 5）。这 SPPVAD系统原型设计/制造/体外测试将在W-Z Biotech进行，而体内将进行 动物研究将在肯塔基大学进行。项目完成后，商业化的sppvad 系统将仅通过微创单套管为严重的CS患者提供全部LV支持。