PDF(Pubmed)
Abstract：
Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6-55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.
摘要：
冷藏（CSS）长达6小时是心脏保存的黄金标准。虽然一些储存超过6小时的心脏已经被移植，更长的CSS时间增加了移植后的死亡率。Transmedics®器官护理系统（OCS™）是唯一获得FDA批准的商业系统，可在静息模式下使用主动脉灌注（Langendorff方法）使用常温异位心脏灌注（NEHP）提供CSS的替代方法。然而,它也仅限于6小时，并且缺乏对心脏功能的客观评估。开发一种可以在NEHP条件下灌注心脏超过24小时的系统可以促进器官康复，扩大捐赠池，和客观的功能评价。密歇根大学的体外生命支持实验室致力于将NEHP延长至>24小时，并对NEHP期间的心脏活力进行客观评估。使用血液来源的灌注液（白细胞/血小板耗尽的血液）开发了用于主动脉（Langendorff）灌注的NEHP系统。将不同大小（6-55kg）的猪心脏（n=42）分为五组，并在24小时内对NEHP进行了各种干预，并在三个仔猪（小尺寸）心脏组中进行了研究：（1）无干预的对照NEHP（n=15）；（2）NEHP血浆交换（n=5）；（3）NEHP心房血液滤过（n=10）和两个成年（NEi5）心脏组（所有接受NEHP+干预的心脏（n=27）成功灌注24小时，而14个(93.3%)对照心脏在10到21小时内衰竭，1个对照心脏（6.6％）持续24h。仔猪血液滤过和血浆置换组的心脏表现优于对照组。iLA灌注组（n=7）中的较大心脏允许实时心脏功能评估，并在NEHP的24小时内保持稳定。这些结果表明，使用我们的NEHP灌注技术将心脏保存24小时是可行的。延长保存时间超过24小时，感染控制,和营养支持都需要优化。这证明了以下概念:NEHP具有通过以下方式增加器官库的潜力:(1)考虑先前丢弃的心脏;(2)对心脏功能进行客观评估;(3)增加供体/受体距离;以及(4)开发心脏特异性灌注疗法。
