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

基本信息

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
项目类别：
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

项目摘要

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）支持允许使用先天性心脏病或心肌病的体重更大，对于复杂的手术矫正或心脏更可行移植。柏林心脏的excor，已通过FDA批准用于儿科LVAD应用。虽然这个设备是在体外，流出移植物可能仍会产生冠状动脉/心脏压缩。我们的最终目标是为新生儿和老年患者开发一个侵入性和可靠的LVAD系统。这启用技术是双管套管（DLC），它从顶点插入主动脉。耦合使用现有的血液泵，该DLC从LV中撤出血液，并将血液输送到主动脉中，卸载 LV。我们的基于DLC的LVAD仅需要一个一个站点，侵入性的先端插管较少。优点是： 1）没有流出移植物和相关的心脏/冠状动脉压缩； 2）不需要心肺旁路和相关的输血； 3）为将来的复杂心脏手术提供了更多侵入性胸骨切开术。这对主动脉（TAA）DLC的跨行动可实现高性能的体体/体外LVAD，并允许为氰化心脏病的添加气体交换器。我们的I阶段研究证明了基于TAA DLC 新生儿LVAD系统非常容易通过左下胸腔切开术植入，并有效地卸下了LV 6个小时，不增加自由血红蛋白，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广告质量的TAA DLC原型用于较小的新生儿施用和为期5天的生存羔羊研究。具体的目标1：设计，制造和替补测试高效率，商业质量TAA DLC原型用于较小的新生儿施用和体内羔羊研究中的5天生存。 TAA DLC将由一块增强的聚氨酯。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固定在顶端和胸壁上卧床用途。将开发13 fr/10 fr taa DLC用于2-4 kg新生儿羔羊急性研究和19 fr/15 FR TAA DLC将为4周大的羔羊（20公斤）生存研究开发。最终原型将进行测试性能，可靠性和溶血。三十天的耐用性将在37％的甘油中进行测试。具体目标2：测试新的13/10 FR TAA DLC在2-4 kg Neonate Lamb中测试（n = 5）。这个6小时的研究旨在证明适用于临床新生儿LVAD应用的TAA DLC。我们将调查TAA部署的便利以及体内性能以及通过延伸输注套管的潜在主动脉瓣阻塞。具体的目标3：在4周大的新生儿羔羊（n = 5）中测试TAA DLC原型5天LVAD施用。这个4周大的羔羊仍然被认为是新生儿，但几乎完全断奶，使我们能够表演5天生存研究。这项体内研究将测试性能，可靠性，耐用性和生物相容性。因此 SBIR赠款完成，商业化的TAA DLC将提供侵入性较小的Neonate LVAD。