Metabolic Modeling for Cadaveric Organ Resuscitation

尸体器官复苏的代谢模型

• 批准号: 9115174
• 负责人: Korkut Uygun
• 金额: $ 40.57万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115174
• 关键词: Algorithm Design; Algorithms; Biological Preservation; Cardiac Death; Cessation of life; Clinical; Complex; Data; Development; Devices; Engineering; Ensure; Goals; Healthcare; Injury; Ischemia; Lead; Least-Squares Analysis; Liver; Liver Cirrhosis; Liver Failure; Metabolic; Methods; Modality; Modeling; Organ; Organ Donor; Organ Preservation; Organ Transplantation; Organ Viability; Outcome; Perfusion; Process; Rattus; Recovery; Research; Resuscitation; Science; Survival Rate; System; Technology; Testing; Time; Translations; Transplantation; Validation; Work; base; body system; chronic liver disease; design; indexing; liver function; liver metabolism; liver transplantation; metabolic profile; novel; prevent; success

DESCRIPTION (provided by applicant): ABSTRACT Chronic liver disease and cirrhosis causes about 30,000 deaths annually in the US, 4,000 of which are directly due to lack of a donor liver available for transplant. These numbers could be reduced dramatically should the donor organ pool be expanded by rendering marginal cases, such as Donors obtained after Cardiac Death (DCD), transplantable. It is estimated that about 6,000 cadaveric livers/yr are only marginally damaged by ischemia post-cardiac death and could be resuscitated for transplantation. There is evidence from our lab and others that machine perfusion is a very promising approach for recovering cadaveric organs that would be otherwise rejected from the donor pool. However, clinical realization of such a machine perfusion device requires sophisticated algorithms that ensure tight control of the system, maximize the viability of the organ and accurately assess if the liver is ready for transplantation at the end of perfusion. There is a significant gap of algorithms designed for such an organ viability maximization task, which prevents clinical translation of these technologies and vertical advancement of the field. Our long-term goal is to develop novel engineering strategies to enable efficient transplantation of marginal donor organs and reduce deaths due to organ shortage. The objective of the proposed study is to develop a dynamic, online method to assess liver viability during perfusion and employ it to optimize liver metabolism to enhance recovery from ischemia. The central hypothesis to be tested here is that the liver viability during perfusion is correlated to liver metabolic function during machine perfusion. The work described here is expected to generate a dynamic, on-line liver viability score which can be used to assess the condition of the donor organs prior to transplantation surgery, ultimately reducing the guesswork involved in transplantation of marginal donor organs. The results of this work will also have a positive impact on engineering science by establishing the basis for integration of process design & control of these complex, dynamic organ preservation systems. The work is also expected to lead to improvements in healthcare by accelerating development of sophisticated organ preservation modalities and reducing deaths due to liver failure.

描述（由申请人提供）： 摘要 在美国，慢性肝病和肝硬化每年导致约 30,000 人死亡，其中 4,000 人直接由于缺乏可供移植的供体肝脏而导致。如果通过使边缘病例（例如心源性死亡（DCD）后获得的供体）可移植来扩大供体器官库，这些数字可能会大幅减少。据估计，每年约有 6,000 具尸体肝脏因心源性死亡后的缺血而受到轻微损害，可以进行复苏以进行移植。我们的实验室和其他实验室的证据表明，机器灌注是一种非常有前途的恢复尸体器官的方法，否则这些器官可能会被供体池拒绝。然而，这种机器灌注设备的临床实现需要复杂的算法，以确保对系统的严格控制，最大限度地提高器官的活力，并在灌注结束时准确评估肝脏是否已准备好进行移植。为此类器官活力最大化任务设计的算法存在显着差距，这阻碍了这些技术的临床转化和该领域的垂直发展。 我们的长期目标是开发新颖的工程策略，以实现边缘供体器官的有效移植并减少因器官短缺而导致的死亡。拟议研究的目的是开发一种动态在线方法来评估灌注过程中的肝脏活力，并利用它来优化肝脏代谢以促进缺血恢复。这里要测试的中心假设是灌注期间的肝脏活力与机器灌注期间的肝脏代谢功能相关。 这里描述的工作预计将产生动态的在线肝脏活力评分，可用于在移植手术前评估供体器官的状况，最终减少边缘供体器官移植中涉及的猜测。这项工作的结果还将通过为这些复杂的动态器官保存系统的过程设计和控制的集成奠定基础，对工程科学产生积极影响。这项工作预计还将通过加速复杂的器官保存方式的发展并减少因肝衰竭而导致的死亡来改善医疗保健。