Department of Anaesthesiology, University of Hong Kong, Room 424, K Block, Queen Mary Hospital, Pokfulam Road, Hong Kong.
J Cardiovasc Pharmacol. 2012 Aug;60(2):172-8. doi: 10.1097/FJC.0b013e31825e2195.
Central opioid receptor activation triggers cardioprotection against ischemia reperfusion injury, independent of peripheral opioid receptor activity. Using a rodent model of myocardial ischemia reperfusion injury with infarct size as the primary outcome, we tested the hypothesis that spinal opioids confer this beneficial effect via a neural pathway. Intrathecal morphine reduced the infarct size compared with control (23% ± 7% vs. 58% ± 3%, respectively, P < 0.01). Prior antagonism of the autonomic pathway, and the receptors for bradykinin, calcitonin gene-related peptide, and the KATP channel, respectively, abolished this cardioprotection (54% ± 13%, 52% ± 10%, 56% ± 9%, and 49% ± 8%, respectively, P < 0.05). In a second set of experiments, we demonstrated that the increased expression of myocardial phosphorylated-Akt and endothelial nitric oxide synthase induced by intrathecal morphine was blocked by prior administration of hexamethonium. These findings support the notion that spinal opioid receptors stimulate a neural pathway that uses nonopioid neurotransmitters to confer cardioprotection from ischemia reperfusion injury. The use of intrathecal morphine for this purpose has potential clinical application, and it is already being used in the perioperative period to provide prolonged analgesia.
中枢阿片受体激活触发对缺血再灌注损伤的心脏保护作用，而不依赖于外周阿片受体活性。使用心肌缺血再灌注损伤的啮齿动物模型，以梗塞面积为主要结局，我们测试了这样一个假设，即脊髓阿片类药物通过神经途径赋予这种有益作用。鞘内吗啡与对照组相比，减少了梗塞面积（分别为 23%±7%和 58%±3%，P<0.01）。预先拮抗自主神经途径，以及缓激肽、降钙素基因相关肽和 KATP 通道的受体，分别消除了这种心脏保护作用（分别为 54%±13%、52%±10%、56%±9%和 49%±8%，P<0.05）。在第二组实验中，我们证明了鞘内吗啡诱导的心肌磷酸化-Akt 和内皮型一氧化氮合酶表达增加被六烃季铵预先给药所阻断。这些发现支持这样一种观点，即脊髓阿片受体刺激一种神经途径，该途径使用非阿片类神经递质来提供缺血再灌注损伤的心脏保护作用。为此目的使用鞘内吗啡具有潜在的临床应用价值，它已经在围手术期用于提供延长的镇痛。
