Remote ischaemic pre- and delayed postconditioning - similar degree of cardioprotection but distinct mechanisms.

Remote ischaemic pre- and delayed postconditioning - similar degree of cardioprotection but distinct mechanisms.
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DOI:
10.1113/expphysiol.2012.064923
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发表时间:
2012-08
影响因子:
2.7
通讯作者:
Gourine A
Gourine A
中科院分区:
医学4区
文献类型:
--
作者:
Basalay M;Barsukevich V;Mastitskaya S;Mrochek A;Pernow J;Sjöquist PO;Ackland GL;Gourine AV;Gourine A

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心肌缺血-再灌注损伤可通过在心肌缺血(MI)之前或期间对位于离心脏一定距离处的外周组织施加缺血-再灌注事件而显著减少;这种现象称为远程缺血条件(RIc)。在这里,我们比较了RIc刺激在MI之前、期间和MI后不同时间点应用时RIc在保护心脏方面的功效。大鼠心肌缺血再灌注损伤模型包括左冠状动脉闭塞30分钟,然后再灌注120分钟。远端缺血预处理诱导15分钟闭塞股动脉,并赋予了类似程度的心脏保护时,应用25分钟前MI,10或25分钟后MI的发病,或开始10分钟后再灌注。这些RIc刺激分别使梗死面积减少了54、56、56和48%(均P < 0.001)。再灌注期30分钟的远程缺血预处理是无效的。只有在心肌梗死前给予辣椒素激活感觉神经才能有效地保护心脏。迷走神经切断术或周围缺血组织的去神经支配都完全取消心肌梗死前应用RIc诱导的心脏保护作用。迷走神经切断术或外周去神经支配均不影响延迟性远程后处理的神经保护作用。这些结果表明,RIc赋予有效的心脏保护,即使在心肌再灌注开始后显著延迟应用。远程预处理的脑保护主要依赖于远程器官的传入神经支配和完整的副交感神经活动,而延迟远程后处理似乎依赖于不同的信号通路。
Myocardial ischaemia–reperfusion injury can be significantly reduced by an episode(s) of ischaemia–reperfusion applied prior to or during myocardial ischaemia (MI) to peripheral tissue located at a distance from the heart; this phenomenon is called remote ischaemic conditioning (RIc). Here, we compared the efficacy of RIc in protecting the heart when the RIc stimulus is applied prior to, during and at different time points after MI. A rat model of myocardial ischaemia–reperfusion injury involved 30 min of left coronary artery occlusion followed by 120 min of reperfusion. Remote ischaemic conditioning was induced by 15 min occlusion of femoral arteries and conferred a similar degree of cardioprotection when applied 25 min prior to MI, 10 or 25 min after the onset of MI, or starting 10 min after the onset of reperfusion. These RIc stimuli reduced infarct size by 54, 56, 56 and 48% (all P < 0.001), respectively. Remote ischaemic conditioning applied 30 min into the reperfusion period was ineffective. Activation of sensory nerves by application of capsaicin was effective in establishing cardioprotection only when elicited prior to MI. Vagotomy or denervation of the peripheral ischaemic tissue both completely abolished cardioprotection induced by RIc applied prior to MI. Cardioprotection conferred by delayed remote postconditioning was not affected by either vagotomy or peripheral denervation. These results indicate that RIc confers potent cardioprotection even if applied with a significant delay after the onset of myocardial reperfusion. Cardioprotection by remote preconditioning is critically dependent on afferent innervation of the remote organ and intact parasympathetic activity, while delayed remote postconditioning appears to rely on a different signalling pathway(s).
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