A systematic approach for an improved patient-device-connection to allow a long-term lung assist (ConnLA)

SPP 2014的目标是使研究能够支持长期植入式肺辅助系统的发展。体外肺辅助（ECLA）系统的插管仍然是不希望的并发症的来源，如由于插管位置不正确引起的再循环，避开的身体部位缺血，以及由于非生理性流动条件在插管尖端形成（微）血栓。这些并发症可能导致无效和可能有害的治疗，并减少ECLA系统的操作时间，因为凝血和堵塞。后者需要更高频率的成分变化，这增加了患者的风险。因此，一种新的系统方法将ECLA系统连接到患者是必要的，它解决了这些并发症，因此可能是迈向长期稳定和可植入的人工肺系统的重要一步。目前的项目旨在替代传统使用的插管，如直接连接血管的血流动力学优化移植物。这样做的目的是提供可靠的血液流入体外回路，而不形成（微）血栓和/或防止导管尖端吸入血管壁，另一方面防止含氧血液回流，这对血管壁造成低剪切应力，与自然血流混合良好，不会再循环到退出点。为了实现这一目标，需要确定针对不同肺部疾病实体的治疗概念的最小和最大体外血流量需求（例如，肺辅助单纯去除CO2或静脉-静脉ECLA联合氧合和CO2去除）。在成像方法的支持下，将确定合适的血管，并利用数值模拟和流动可视化方法研究最佳移植物形状和最佳位置，包括流动角度、混合、剪切应力和相对于其他解剖结构的空间位置。基于这些数据，新的移植物设计将在体外进行探索和测试。最后，这些体外试验结果将在急性动物试验系列中得到验证。计划在第二个批准期进行慢性动物试验系列的进一步体内试验。计划项目持续时间：36个月，随后是36个月的连续申请

Aim of SPP 2014 is to enable research to support the development of long-term implantable lung assist systems. The cannulation of Extracorporeal Lung Assist (ECLA) systems is still a source of undesired complications such as recirculation due to a malposition of the cannula, ischemia of the averted body parts, and formation of (micro-)thrombi at the cannula tip due to non-physiologic flow conditions. These complications can result in an ineffective and possibly harming treatment and a reduction of the operating time of the ECLA system due to clotting and clogging. The latter requires a higher frequency of component changes which adds to the risks for the patient.Therefore, a new systematic approach to connect the ECLA system to the patient is necessary, which addresses these complications and thus may represent an important step towards a long-term stable and implantable artificial lung system. The present project aims for an alternative to conventionally used cannula such as hemodynamically optimized grafts directly connected to blood vessels. The intention is to provide a reliable blood flow into the extracorporeal circuit without (micro-)thrombi formation and/or prevention of suction of the cannula tip to the vessel wall on one hand and a return of the oxygenated blood on the other hand, which causes low shear stress to the vessel wall, provides a good mixing with the natural blood flow and no recirculation to the withdrawal point.In order to accomplish this aim, the minimal and maximal demand of extracorporeal blood flow needs to be determined for therapy concepts tailored to different entities of lung disease (e. g. lung assist with mere CO2 removal or combined oxygenation and CO2 removal with venovenous ECLA). Suitable blood vessels will be identified with the support of imaging methods and the optimal graft shape and optimal positioning, regarding angle of flow, mixing, shear stresses, and spatial position relative to other anatomic structures, will be investigated using numerical simulation and flow visualization methods. Based on these data, novel graft designs will be explored and tested in vitro. Finally, these in-vitro test results will be validated in an acute animal test series. Further in-vivo testing in a chronic animal test series is planned for a second grant period.Planned project duration: 36 month followed by a continuative application for 36 month