Bolling S F, Su T P, Childs K F, Ning X H, Horton N, Kilgore K, Oeltgen P R
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor 48109-0344, USA.
Transplantation. 1997 Jan 27;63(2):326-9. doi: 10.1097/00007890-199701270-00026.
Cardiac transplant is hindered by donor shortage and preservation time. Extended extracorporeal preservation could increase the number and distribution of hearts for transplantation. Interestingly, mammalian hibernation biology closely parallels the altered cardiac cellular physiology noted with hypothermic organ storage. The present study undertook to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic storage in a nonhibernating mammalian model. To study this hypothesis, isolated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standard cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE), which mimics natural hibernation, or preperfusion with DADLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed pressure, coronary flows, and myocardial oxygen consumption were significantly improved with DADLE pretreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation following prolonged storage ischemia. This study demonstrates that hibernation protection with DADLE is beneficial for prolonged cardiac storage. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.
心脏移植受到供体短缺和保存时间的限制。延长体外保存时间可以增加可用于移植的心脏数量并扩大其分配范围。有趣的是，哺乳动物的冬眠生物学与低温器官保存时所观察到的心脏细胞生理学变化极为相似。本研究旨在测试在非冬眠哺乳动物模型中，使用冬眠诱导触发因素进行处理是否能改善长时间缺血保存后的心肌功能恢复。为了研究这一假设，先记录离体兔心脏的基线功能和代谢参数，然后分别给予单纯低温保存、标准心脏停搏液，或含有1毫克/千克D - 丙氨酸2 - 亮氨酸5 - 脑啡肽（DADLE）的心脏停搏液（DADLE可模拟自然冬眠），或者在心脏停搏液缺血前25分钟以2毫摩尔的剂量给予DADLE预灌注15分钟。随后，心脏在4摄氏度下进行18小时的全心缺血保存。与保存和再灌注后的所有其他组相比，DADLE预处理显著改善了等容收缩压、冠状动脉血流量和心肌耗氧量。此外，长时间保存缺血后，DADLE处理的心脏在组织学超微结构保存方面表现更佳。本研究表明，DADLE诱导的冬眠保护对延长心脏保存时间有益。使用冬眠诱导触发因素在器官保存方面具有前景，值得进一步开展机制研究。
