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）是一种严重的心输出量（CO）减少的疾病， 40- 50%在重度CS中，低CO引起的终末器官灌注不足导致多器官衰竭和左室肥厚。 心室（LV）前负荷增加LV壁应力。对于重度CS，静脉动脉体外膜 氧合是最常用的，也是重建循环的最快方法，但在> 50%的患者中， 这些病人。经皮机械循环支持（MCS）器械用于严重CS，但可能 不能完全稳定循环。非经皮MCS器械提供全面的心脏支持，但需要开放 胸部手术安装。我们的目标是开发一个紧凑的，单端口，脉动心室辅助装置 （sppVAD）用于全LV支持，采用微创单插管技术进行植入。 与连续流LVAD相比，我们的sppVAD系统可以在与 自体心脏进行反搏我们形成sppVAD系统的使能技术是 单腔套管（VSLC）和无阀单口隔膜排量泵（spDDP）。我们 创新的sppVAD系统特点：1）通过一个VSLC进行经心尖至主动脉的微创安装 2）spDDP较小，无进、出口阀，死腔较大; 3)由于通过作为入口和出口的VSLC通过LV的路径较短，因此血液阻力较低 插管; 4）依赖性全LV卸载; 5）反搏时潜在LV内部/每搏功降低 抽气W-Z Biotech制作了sppVAD系统的初始原型，其具有3.1 L/min的泵送流量， 模拟环测试中的80 mm Hg后负荷。我们在第一阶段SBIR的目标是开发/制造新的 sppVAD系统的工作原型（VSLC和spDDP），并在模拟环路中测试sppVAD系统原型 和重度CS绵羊模型。具体目标1：开发/制造/台架测试新的工作原型 sppVAD系统（VSLC和spDDP）。22 Fr VSLC主体将采用记忆合金丝加固 聚氨酯（PU）。VSLC壁上的两个单向入口阀将位于LV中用于抽血。两个单向 靠近头端的VSLC壁上的出口阀和VSLC头端上的单向出口阀将位于升主动脉中，用于血液 交付. spDDP将具有刚性PU外壳、柔软的柔性PU隔膜和50 mL泵 音量.在spDDP上仅制作一个3/8”血液端口，用于直接连接至VSLC。该sppVAD系统 将在台架模拟循环中进行测试。具体目标2：在严重CS中测试sppVAD系统原型 绵羊模型我们的严重CS绵羊模型将用于测试我们的sppVAD系统原型，以便于 插入/展开、LV卸载性能、反搏能力和6小时可靠性（n=5）。的 sppVAD系统原型设计/制造/体外试验将在W-Z Biotech完成，而体内试验将在W-Z Biotech完成。 动物研究将在肯塔基州大学进行。项目完成后，商业化的sppVAD 系统将仅通过微创单次插管为严重CS患者提供全LV支持。