Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China.
Life Sci. 2012 Oct 29;91(17-18):860-5. doi: 10.1016/j.lfs.2012.08.037. Epub 2012 Sep 13.
Remote preconditioning is a powerful and potentially clinically viable mode of cardioprotection. The mechanisms underlying its transmission process have not been extensively studied. The aim of this study was to test the hypothesis that spinal opioid receptors are involved with signal transmission of remote cardiac preconditioning.
Two established models of remote preconditioning were used, one using intermittent ischaemia of the lower limb (remote ischaemic preconditioning, RIPC) and the other by stimulation of cutaneous pain fibres via an abdominal incision (remote preconditioning of trauma, RPOT). Classic ischaemic preconditioning (IPC) was used as positive control. Selective blockade of spinal opioid receptors was achieved through intrathecal injection of naloxone methiodide, a compound not known to cross the blood-brain barrier.
The prior introduction of naloxone methiodide abolished the cardioprotective effects of RIPC, RPOT but not IPC, as assessed by infarct size as a percentage of area at risk following 30min of ischaemia and 120min reperfusion. Of the specific receptor antagonists, only that specific for the mu receptor subtype, and not delta or kappa receptor, block the protective response.
These results suggest that the central nervous system at the spinal cord level is involved with the relaying of signals between the afferent and efferent arms of remote preconditioning.
远程预处理是一种强大且具有潜在临床可行性的心脏保护模式。其传输过程的机制尚未得到广泛研究。本研究旨在检验以下假设，即脊髓阿片受体参与远程心脏预处理的信号传递。
使用两种已建立的远程预处理模型，一种使用下肢间歇性缺血（远程缺血预处理，RIPC），另一种通过腹部切口刺激皮肤痛觉纤维（创伤远程预处理，RPOT）。经典缺血预处理（IPC）用作阳性对照。通过鞘内注射纳洛酮甲碘化物来实现脊髓阿片受体的选择性阻断，这是一种不通过血脑屏障的化合物。
预先引入纳洛酮甲碘化物消除了 RIPC、RPOT 的心脏保护作用，但 IPC 没有，如缺血 30 分钟和再灌注 120 分钟后，梗死面积占风险面积的百分比所示。在特定的受体拮抗剂中，只有针对 mu 受体亚型的拮抗剂，而不是 delta 或 kappa 受体拮抗剂，阻断了保护反应。
这些结果表明，中枢神经系统在脊髓水平参与了远程预处理的传入和传出臂之间的信号传递。
