An Organ Perfusion Stent as an Alternative to Surgery in Donor Organ Recovery

项目摘要 在美国，用于移植的器官严重短缺，只有四分之一的人 12万名需要器官移植的病人等待移植的病人的费用 医疗保健系统每年总计数百亿美元。同时，成千上万的器官被丢弃 由于供血不足造成的损伤（缺血性损伤），每年都会发生一次。的 心源性死亡捐献者同意捐献的传统模式是停止 心肺生命支持，使器官没有足够的血液灌注，直到心脏停止。这 与非捐赠者的患者的通常临终护理选择形成对比，其中患者及其家属 家庭可以选择停止对某些身体功能的生命支持（CPR，维持血压的药物， 透析或插管），同时维持其他器官的生命支持。我们的提案详细说明了 创新的针刺方法，以保持选择性的血液流向器官，同时允许供体心脏， 以自己的方式失败。这与先前报道的加速心脏死亡的方法形成对比， 违背了道德原则。我们已经检查了一个商业混合原型器官灌注支架（OPS）， 一项初步研究表明，改善了血液输送到器官，而不会对心脏功能产生负面影响。 认识到当前成像在危重患者（例如， 为了治疗供体，我们还开发了一种便携式射频（RF）方法，用于床边支架定位。 当前方法的主要目标是证明一种新的定制OPS 提供针对缺血性器官损伤的客观保护。我们的调查将开始与优化 这种新型双腔支架的机械性能，以确保快速部署，成功隔离， 内脏动脉和简化的回收。接下来，我们将优化支架的血流动力学，以确保 均匀的血液流向器官。一个小型化的射频天线将直接打印到支架上 结构在器官供体的猪模型中，OPS将通过针刺入路展开， 在密切的心脏监测下使用便携式X射线和RF标签方法的定位方法将 与金标准血管造影术进行比较以确定器械定位。经过60分钟的模拟 间隔活检的灌注不良，支架和对照动物将通过每日评估恢复 来监测器官功能术后两天，将对肝脏、胰腺和肾脏活检进行评价 组织学上的缺血性变化为了在人类环境中研究该设备， 然后将评估人体解剖结构在心脏跳动中的成功部署和器官灌注 人体尸体模型。总之，我们预计，最终，器官灌注支架可以允许每一个 在尊重器官回收伦理的情况下，获得同意的捐赠者成功捐赠器官用于移植。

PROJECT SUMMARY In the United States, there is a critical shortage of organs for transplant, with only a quarter of the 120,000 patients in need of an organ actually receiving one. The cost of patients awaiting transplant to the healthcare system totals tens of billions of dollars each year. Meanwhile, thousands of organs are discarded each year as a result of injury from inadequate blood flow (ischemic injury) as the donor is dying. The traditional paradigm for consented Donation after Cardiac Death donors has been to discontinue cardiopulmonary life support, leaving organs without adequate blood perfusion until the heart stops. This contrasts with the usual end of life care options for patients who are not donors, in which patients and their families can elect to withhold life support for some body functions (CPR, agents to maintain blood pressure, dialysis, or intubation) while at the same time maintaining life support for other organs. Our proposal details an innovative needlestick approach to maintain selective blood flow to the organs while allowing the donor heart to fail on its own terms. This contrasts to previously reported approaches which would accelerate cardiac death, against ethical principles. We have examined a commercial hybrid prototype Organ Perfusion Stent (OPS) in a pilot study and shown improved blood delivery to organs without a negative impact on cardiac function. Recognizing the logistical challenges of current imaging for device placement in a critically ill patient, such as a donor, we have also developed a portable radiofrequency (RF) approach for stent positioning at bedside. The primary objective of the current approach is to demonstrate that a novel custom made OPS provides objective protection against ischemic organ injury. Our investigation will begin with optimizing the mechanical properties of this novel dual-chambered stent to ensure rapid deployment, successful isolation of the visceral arteries, and simplified retrieval. Next, we will optimize the hemodynamics of the stent to ensure uniform blood flow to the organs. A miniaturized RF antenna will then be directly printed onto the stent structure. In a porcine model of the organ donor, an OPS will be deployed by a needlestick access while under close cardiac monitoring. Positioning approaches using both portable X-ray and RF tag approaches will be compared to gold standard angiography for device positioning. Following a 60 minute period of simulated malperfusion with interval biopsies, both stented and control animals will be recovered with daily assessment to monitor organ function. At two days postoperatively, liver, pancreas and kidney biopsies will be evaluated for ischemic changes histologically. To investigate this device in a human context, an OPS calibrated for human anatomy will then be evaluated for successful deployment and organ perfusion in a heart beating human cadaver model. In summary, we expect that ultimately, an Organ Perfusion Stent may allow every consented donor to successfully donate organs for transplant while respecting the ethics of organ recovery.