Pickard Jack M J, Davidson Sean M, Hausenloy Derek J, Yellon Derek M
The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
Basic Res Cardiol. 2016 Jul;111(4):50. doi: 10.1007/s00395-016-0568-z. Epub 2016 Jun 23.
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.
远程缺血预处理（RIC）所提供的心脏保护作用是通过一种复杂机制介导的，该机制涉及感觉传入神经、迷走神经以及一种血液中携带的体液因子的释放。然而，尚不清楚这种保护因子的释放是依赖于迷走神经激活还是独立发生。本研究旨在评估RIC神经和体液途径的相互依赖性，重点关注迷走神经和心脏固有神经节。在第一项研究中，麻醉大鼠在进行RIC（4×5分钟肢体缺血-再灌注）或假RIC之前立即接受双侧颈迷走神经切断术或假手术。将静脉血浆通过12 - 14 kDa的膜进行透析，并将透析液灌注到未经处理的离体大鼠心脏，然后进行35分钟的左前降支缺血和60分钟的再灌注。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）。在进行上述缺血-再灌注之前，在存在神经节阻滞剂六甲铵或毒蕈碱拮抗剂阿托品的情况下，制备透析液并灌注到未经处理的离体大鼠心脏。从接受RIC处理的大鼠收集的透析液使未经处理的大鼠心脏梗死面积从40.7±6.3%降至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%，与RIC透析液相比p<0.05）。在第二项研究中，给予50μM六甲铵（45.8±2.5%）或100 nM阿托品（36.5±3.4%）消除了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脏固有神经节诱导心脏保护作用。
