使用“天然”冬眠诱导触发因素进行心肌保护。

Use of "natural" hibernation induction triggers for myocardial protection.

作者信息

Bolling S F, Tramontini N L, Kilgore K S, Su T P, Oeltgen P R, Harlow H H

机构信息

Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, USA.

出版信息

Ann Thorac Surg. 1997 Sep;64(3):623-7. doi: 10.1016/s0003-4975(97)00631-0.

DOI:10.1016/s0003-4975(97)00631-0

PMID:9307448

Abstract

BACKGROUND

Hypothermic cardioplegia provides adequate myocellular protection, yet stunning and dysfunction remain significant problems. Interestingly, the subcellular changes of hibernation parallel the altered biology of induced cardiac ischemia, but are well tolerated by hibernating mammalian myocardium. Hibernation induction trigger (HIT) from winter-hibernating animal serum induces hibernation in active animals. Hibernation induction trigger is opiate in nature and is similar to the delta 2 opioids.

METHODS

To determine whether HIT could improve myocardial recovery following global ischemia, we gave 37 isolated rabbit hearts either standard cardioplegia or cardioplegia containing summer-active woodchuck, hibernating woodchuck, or black bear HIT serum or a delta 2 opioid, D-Ala2-Leu5-enkephalin, before 2 hours of global ischemia.

RESULTS

Hibernation induction trigger appeared not to have an active mechanism during ischemia, as all hearts had equal recovery. In contrast, when examining for a preischemia mechanism, 23 additional rabbits received 3 days pretreatment with summer-active woodchuck or HIT hibernating woodchuck or black bear serum, or were preperfused with D-Ala2-Leu5-enkephalin or D-pen2,5-enkephalin, a-delta 1 opioid, again before 2 hours of global ischemia. Postischemic ventricular function, coronary flows, myocardial oxygen consumption, and ultrastructural preservation were all significantly improved with HIT and D-Ala2-Leu5-enkephalin pretreatment.

CONCLUSION

"Natural" HIT protection is superior to standard cardioplegia alone and may have clinical application.

摘要

背景

低温心脏停搏可提供充分的心肌细胞保护，但心肌顿抑和功能障碍仍是严重问题。有趣的是，冬眠的亚细胞变化与诱导性心肌缺血的生物学改变相似，但冬眠的哺乳动物心肌对此具有良好的耐受性。来自冬季冬眠动物血清的冬眠诱导触发因子（HIT）可使活跃动物进入冬眠状态。冬眠诱导触发因子本质上是阿片类物质，与δ2阿片类物质相似。

方法

为了确定HIT是否能改善全心缺血后的心肌恢复情况，我们在37个离体兔心进行2小时全心缺血前，分别给予标准心脏停搏液或含有夏季活跃土拨鼠、冬眠土拨鼠或黑熊HIT血清或一种δ2阿片类物质D - Ala2 - Leu5 - 脑啡肽的心脏停搏液。

结果

在缺血期间，冬眠诱导触发因子似乎没有积极作用机制，因为所有心脏的恢复情况相同。相比之下，在研究缺血前机制时，另外23只兔子在进行2小时全心缺血前3天，分别接受夏季活跃土拨鼠或HIT冬眠土拨鼠或黑熊血清预处理，或预先灌注D - Ala2 - Leu5 - 脑啡肽或D - pen2,5 - 脑啡肽（一种α - δ1阿片类物质）。HIT和D - Ala2 - Leu5 - 脑啡肽预处理后，缺血后心室功能、冠脉血流、心肌氧耗及超微结构保存均显著改善。