EAGER: Multiscale Analysis of Human Heart Cooling Protocols

目前器官移植的主要问题是器官从采集到外科移植到受者体内的时间相对较短。在器官保存中，冷保存仍被认为是最好的方法。降低细胞、组织和器官的温度会降低它们的化学反应速率，从而降低它们的代谢衰变速率。在目前使用的标准心脏冷却程序中，提取的人类心脏被浸泡在一个装有盐水溶液的容器中，温度略高于冰水。目前使用这种冷却方法的心脏在移植中存活的极限只有4.5小时，之后心脏就会被丢弃。因此，由于心脏接受者住得太远，大量可存活的捐赠心脏被丢弃。这项研究的最终目标是将提取的人类心脏的生存能力延长到10.5小时以上，最近PI通过计算证明这是初步可行的。这将为空运提供超过8小时的时间，从而使心脏能够被运送到人口稠密的北美大陆的任何地方进行移植。这个项目的结果应该提供一个既可行又广泛适用的器官冷却方案的理解。该项目的目标是应用先进的数值分析和快速冷却人类心脏的优化概念，探索减少代谢衰变并将其用于长途运输到移植地点的目的。重点将是执行一个多尺度的分析，在现实的人的心脏，包括心外膜和血管内的共轭传热。风险在于，增加这种几何和数值复杂性可能不会提高冷却速度。为了实现这一目标，移植的心脏应该立即开始一个冷却过程，利用接近冰点的水尽可能均匀和快速地冷却心脏，以最大限度地减少新陈代谢对心肌的永久性损伤。在本初步研究中，将首次纳入冷却剂在冠状血管、分支血管和心肌组织微循环中的流动和相应的换热。通过将这些多重长度尺度效应纳入整体强制对流共轭换热分析中，可以期望提高现实人类心脏的冷却速度和均匀性，从而进一步减少代谢衰变，进一步延长可用于运输提取心脏的生存时限。

MULTI-SCALE ANALYSIS OF COOLING PROTOCOLS FOR HUMAN HEARTS The main current problem of organ transplantation is the relatively short time that organs can survive from the moment of their harvesting to the moment of their surgical transplantation into the recipient's body. In organ preservation, cold preservation is still considered as the best method. Lowering the temperatures of cells, tissues and organs lowers their chemical reaction rates, thus lowering their metabolic decay rate. In currently used standard heart cooling procedures, the extracted human heart is kept submerged in a container with saline solution at a temperature slightly above that of freezing water. The current limit for a heart to remain viable for transplantation using this method of cooling is only 4.5 hours, after which the heart is discarded. Consequently, a large number of viable donated hearts are discarded because the recipient of the heart lives too far away. The ultimate objective of this research is to extend the viability of the extracted human heart to more than 10.5 hours, which was recently computationally demonstrated by the PI as preliminarily feasible. This would provide more than 8 hours for air transport, thus enabling hearts to be transported for transplantation anywhere in the populated North American continent. The results of this project should provide an understanding of the proposed organ cooling protocols that are both viable and widely applicable.The objective of this project is to apply advanced numerical analysis and optimization concepts of rapidly cooling human hearts to explore reducing metabolic decay and extending their use for the purpose of long distance transportation to the transplantation site. The focus will be on performing a multi-scale analysis of the conjugate heat transfer in realistic human hearts including epicardiac and intramural blood vessels. The risk is that adding this geometric and numerical complexity might not increase the cooling rate. As part of achieving this goal, the explanted heart should immediately begin a cooling process utilizing nearly-freezing water in order to cool the heart as uniformly and as fast as possible to minimize permanent damage of the heart muscle due to metabolism. In this preliminary research, coolant flow and the corresponding heat transfer in coronary blood vessels, branching intramural vessels and microcirculation in the heart muscle tissue will be included for the first time. By including these multiple length scale effects into the overall forced convection conjugate heat transfer analysis, it could be expected that the speed and uniformity of cooling of the realistic human hearts can be increased, thus decreasing further the metabolic decay and extending further the viability time limit available for transporting the extracted hearts.