Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning.
Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning.
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DOI：
10.1007/s00395-016-0568-z
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发表时间：
2016-07
影响因子：
9.5
通讯作者：
Yellon DM
中科院分区：
文献类型：
--
作者：
Pickard JM;Davidson SM;Hausenloy DJ;Yellon DM
远程缺血条件（RIC）提供的心脏保护是通过一个复杂的机制介导的感觉传入神经，迷走神经，和体液血液传播因子的释放。然而，目前尚不清楚保护因子的释放是否依赖于迷走神经激活或独立发生。本研究旨在评价RIC的神经和体液通路的相互依赖性，重点是迷走神经和心内神经节。在第一项研究中，麻醉大鼠在RIC（4 × 5 min肢体缺血-再灌注）或假RIC前即刻接受双侧颈部迷走神经切断术或假手术。在35分钟左前降支缺血和60分钟再灌注之前，通过12-14 kDa膜透析静脉血浆，并通过未处理的分离大鼠心脏灌注透析液。在第二项研究中，麻醉大鼠接受RIC（4 × 5分钟肢体缺血-再灌注）或对照（假RIC）。在上述缺血-再灌注前，在神经节阻滞剂六甲铵或毒蕈碱拮抗剂阿托品存在下，制备透析液并通过未处理的离体大鼠心脏灌注。从RIC处理的大鼠中收集的透析液将未处理大鼠心脏的梗死面积从40.7 ± 6.3%降低至23.7 ± 3.1%，p < 0.05。双侧颈迷走神经切断术后，RIC透析液的保护作用消失（42.2 ± 3.2%，p < 0.05 vs RIC透析液）。在第二项研究中，给予50 μM六烃季铵（45.8 ± 2.5%）或100 nM阿托品（36.5 ± 3.4%）可消除透析液介导的保护作用。RIC后保护因子的释放依赖于迷走神经的预先激活。此外，该因子似乎通过募集心内神经节诱导心脏保护作用。本文的在线版本（doi：10.1007/s 00395 -016-0568-z）包含补充材料，可供授权用户使用。
The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia–reperfusion) or sham-RIC. Venous blood plasma was dialysed across a 12–14 kDa membrane and dialysate perfused through a naïve-isolated rat heart prior to 35-min left anterior descending ischemia and 60-min reperfusion. In the second study, anesthetised rats received RIC (4 × 5-min limb ischemia–reperfusion) or control (sham-RIC). Dialysate was prepared and perfused through a naïve-isolated rat heart in the presence of the ganglionic blocker hexamethonium or muscarinic antagonist atropine, prior to ischemia–reperfusion as above. Dialysate collected from RIC-treated rats reduced infarct size in naïve rat hearts from 40.7 ± 6.3 to 23.7 ± 3.1 %, p < 0.05. Following bilateral cervical vagotomy, the protection of RIC dialysate was abrogated (42.2 ± 3.2 %, p < 0.05 vs RIC dialysate). In the second study, the administration of 50-μM hexamethonium (45.8 ± 2.5 %) or 100-nM atropine (36.5 ± 3.4 %) abrogated the dialysate-mediated protection. Release of a protective factor following RIC is dependent on prior activation of the vagus nerve. In addition, this factor appears to induce cardioprotection via recruitment of intrinsic cardiac ganglia. The online version of this article (doi:10.1007/s00395-016-0568-z) contains supplementary material, which is available to authorized users.