Innovating Organ Shipment by Studying Environmental Factors which Affect Organs During Cold Preservation

摘要：人体器官运输方式的创新迫在眉睫。虽然有很多 在过去的三十年里，在提高移植存活率和免疫效果方面所做的工作很少 已经完成，以了解如何在运输过程中最佳地护理器官。作为移植领域 聪明地重新考虑器官分配，需要做更多的工作来帮助改善器官运输的过程。 在之前的工作中，我们质疑无人驾驶飞机或无人机按需运送器官是否可能 改善获得可移植器官的机会。器官无人机可能会减少CIT并提高器官利用率。 在最初的无人机实验中，新型遥测设备显示出显著的压力差异， 温度，以及当无人机飞行与传统的固定翼飞行进行比较。这一点特别有趣 因为最近的出版物揭示了器官移动时器官移植结果的不同 空中对抗地面。此外，众所周知，航空公司航班的低压暴露会对器官产生负面影响。 创伤后的功能。目前还没有针对这些因素或它们对可移植器官的影响的研究。 然后，我们在异位心脏的一个小模型中模拟了影响器官的环境因素 移植模型。我们发现，与非振动相比，中度振动会导致存活率降低 红心。移植的心脏显示细胞凋亡和F-肌动蛋白紊乱增加。需要做更多的工作来 确定照顾运输中器官的最适当方式，并减轻运输过程中的潜在风险。 这项建议建立在我们在创新器官运输方面的专业知识基础上。我们假设CIT是 不仅仅是独处的时间，环境因素可能会影响移植物的存活。我们会 分离压力、温度和振动，了解每个因素是如何单独影响移植器官的 更大的目标是实施战略，以减轻每一种风险并改善器官功能。 在目标1中，我们将确定目前尚未测量的影响心脏的实际环境因素 通过汽车、直升机、飞机和无人机进行运输。我们将计算温度、压力和振动，以及 比较每种运输方式的遥测结果。然后我们将评估装运前和装运后的活组织检查 改变细胞黏附分子(ICAM-1、VCAM-1)和细胞骨架肌动蛋白。在目标2中，我们将对这些进行建模 在心脏移植的动物模型中施加压力。供体心脏将经过压力、温度或 震动。主要的结果指标将是移植物存活率。次要结果衡量标准将不是 侵入性经胸超声心动图和组织学检测黏附分子和肌动蛋白，如目标1所示。 在这里，我们将第一次了解环境是如何影响数千个人体器官的 在运输过程中。然后我们将学习多变量冷缺血时间的每个组成部分是如何贡献的 器官功能、免疫反应和移植物存活率。这些发现将共同推动器官领域的研究 坚持不懈地走进下一个十年。

Abstract: There is an urgent and critical need to innovate shipment methods for human organs. While much has been done in the last three decades to improve transplant survival rates and immunologic outcome, little has been done to understand how to optimally care for organs during shipment. As the field of transplantation smartly rethinks organ allocation, more work needs to be done to help improve the process of organ shipment. In prior work, we questioned if on-demand organ shipment with unmanned aircraft, or drones, might improve access to transplantable organs. Organ drones may decrease CIT and improve organ availability. During initial drone experiments, novel telemetry devices showed significant differences in the pressure, temperature, and when drone flight was compared with traditional fixed wing flight. This is particularly interesting because recent publications have revealed differences in organ transplant outcome when organs are moved by air versus ground. Further, it is well known that low-pressure exposure from airline flight negatively impact organ function after trauma. There are no studies addressing these factors or their impact on transplantable organs. We then modeled environmental factors affecting organs in a small model of heterotopic cardiac transplant model. We found that mid-range vibration led to reduced survival when compared with non-vibrated hearts. Explanted hearts showed increases in apoptosis and F-actin derangement. More work is needed to determine the most appropriate way to care for organs in transit and mitigate potential risks during shipment. This proposal builds on our expertise with innovating organ shipment. We hypothesize that CIT is comprised of more than just time alone, and that environmental factors may impact graft survival. We will separate pressure, temperature, and vibration to learn how each factor individually affects transplanted organs with the greater goal of implementing strategies to mitigate each of these risks and improve organ function. In Aim 1 we will determine, presently unmeasured, actual environmental factors that affect hearts during transport by car, helicopter, airplane, and drone. We will calculate temperature, pressure, and vibration, and compare telemetry findings for each shipment modality. We will then assess pre-and-post shipment biopsies for changes cellular adhesion molecules (ICAM-1, VCAM-1) and cytoskeletal actin. In Aim 2, we will model these forces in an animal model of heart transplant. Donor hearts will be pre-treated with pressure, temperature, or vibration. The primary outcome measure will be graft survival. The secondary outcome measure will be non- invasive transthoracic echocardiographic and histology for adhesion molecules and actin as in Aim 1. Here, we will learn for the first time how the environment has been affecting thousands of human organs during shipment. We will then learn how each component of a multi-variable cold ischemia time contributes to organ function, immunological response, and graft survival. Together these findings will launch the field of organ perseveration into the next decade.