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

研究冷藏过程中影响器官的环境因素，创新器官运输

• 批准号: 10689394
• 负责人: Joseph R. Scalea
• 金额: $ 18.88万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689394
• 关键词: ANXA5 gene; Actins; Address; Affect; Air; Aircraft; Animal Model; Animals; Annexins; Apoptosis; Architecture; Atmospheric Pressure; Biopsy; Cardiac Myocytes; Cardiac Output; Caring; Cell Adhesion; Cell Adhesion Molecules; Cell Death; Clinical; Cryopreservation; Data; Data Reporting; Devices; Dimensions; E-Selectin; Environment; Environmental Impact; Environmental Risk Factor; Exposure to; F-Actin; Failure; Future; Goals; Graft Survival; Heart; Heart Transplantation; Helicopter; Hemolysis; Histology; Hospitals; Hour; Human; Immune response; Immunologics; Improve Access; In Situ Nick-End Labeling; In Vitro; Individual; Intercellular adhesion molecule 1; Investigation; Ischemia; Laboratories; Learning; Liver; Measurement; Measures; Mediating; Methods; Modality; Modeling; Monitor; Mus; Muscle Cells; Organ; Organ Survival; Organ Transplantation; Organ failure; Outcome; Outcome Measure; Process; Publications; Reporting; Research Personnel; Risk; Shipping; Ships; Stains; Stroke Volume; Suggestion; Survival Rate; System; Telemetry; Temperature; Thrombosis; Thrombus; Time; Transplantation; Transportation; Trauma; Travel; Vascular Cell Adhesion Molecule-1; Vertebral column; Wing; Work; experimental study; extracellular; foot; graft function; heart function; improved; innovation; natural hypothermia; novel; organ allocation; pressure; primary outcome; secondary outcome; standard of care; transplant model; vibration

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.

翻译后摘要：有一个迫切和关键的需要，创新运输方法的人体器官。虽然大部分 在过去的三十年里，已经做了一些工作来提高移植存活率和免疫结果，但很少 了解如何在运输过程中对器官进行最佳护理。作为移植领域 聪明地重新思考器官分配，需要做更多的工作来帮助改善器官运送的过程。 在之前的工作中，我们质疑用无人驾驶飞机或无人机按需运送器官是否可能 改善可移植器官获取途径。器官无人机可能会降低CIT并提高器官可用性。 在最初的无人机实验中，新型遥测设备显示出压力的显著差异， 温度，以及无人机飞行与传统固定翼飞行的比较。这是特别有趣 因为最近的出版物揭示了器官移植结果的差异， 空中对地面此外，众所周知，航空公司飞行的低压暴露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其对可移植器官影响的研究。 然后，我们在一个异位心脏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，中等振动导致生存率降低 心中移植心脏细胞凋亡和F-肌动蛋白紊乱增加。需要做更多的工作来 确定最适当的方式来照顾转运中的器官，并降低运输过程中的潜在风险。 该提案建立在我们创新器官运输的专业知识基础上。我们假设CIT是 包括的不仅仅是独处的时间，环境因素可能会影响移植物的存活。我们将 分离压力、温度和振动，以了解每个因素如何单独影响移植器官 更大的目标是实施策略来减轻这些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、飞机和无人机运输。我们将计算温度、压力和振动， 比较每种运输方式的遥测结果。然后，我们将评估装运前后的活检， 改变细胞粘附分子（ICAM-1、VCAM-1）和细胞骨架肌动蛋白。在目标2中，我们将对这些模型进行建模 心脏移植动物模型中的力。供体心脏将被预处理的压力，温度，或 振动.主要结果指标是移植物存活率。次要结局指标为非- 如目标1中所述，进行侵入性经胸超声心动图和组织学检查以检测粘附分子和肌动蛋白。 在这里，我们将首次了解环境如何影响数千个人体器官 在装运期间。然后，我们将了解多变量冷缺血时间的每个组成部分如何有助于 器官功能、免疫反应和移植物存活。这些发现将共同启动器官领域 坚持到下一个十年。