Toronto, Ontario, Canada From the Research Institute, The Hospital for Sick Children, and the Division of Plastic and Reconstructive Surgery and the Departments of Surgery and Physiology, University of Toronto.
Plast Reconstr Surg. 2013 Mar;131(3):473-485. doi: 10.1097/PRS.0b013e31827c6e0b.
In autogenous muscle transplantation, unpredictable complications can cause prolonged ischemia, resulting in ischemia-reperfusion injury. The authors investigated the efficacy and mechanism of nicorandil, a nitrovasodilator and adenosine triphosphate-sensitive potassium channel opener, in inducing perioperative protection of muscle flaps from ischemia-reperfusion injury.
Pigs (18.2 ± 2.4 kg) were assigned to one control and eight treatment groups. Bilateral latissimus dorsi muscle flaps were raised after saline administration (control) and 0, 4, 8, 12, 24, 48, 72, and 96 hours after nicorandil administration. Subsequently, flaps were subjected to 4 hours of ischemia and 48 hours of reperfusion. Viability was assessed, and biochemical probes were used to study nicorandil-induced infarct protection.
Protection by nicorandil was biphasic. Infarction reduced from 40.2 ± 1.9 percent (control) to 27.3 ± 1.7 percent and 24.0 ± 2.3 percent (p < 0.05) 0 and 4 hours after nicorandil administration, respectively (early phase protection). No difference was seen between control and treatment groups between 8 and 12 hours after nicorandil administration compared with the control. Infarct protection increased again (p < 0.05) at 24 (22.4 ± 2.0 percent), 48 (25.1 ± 2.1 percent), and 72 hours (28.5 ± 2.1 percent) but not at 96 hours (43.9 ± 4.6 percent) compared with control (late phase protection). The sarcolemmal and mitochondrial channels played a central role in the trigger and mediator mechanisms, respectively. Late protection was associated with lower myeloperoxidase activity and mitochondrial calcium overload and higher adenosine triphosphate content (p < 0.05).
Nicorandil induced 48-hour uninterrupted muscle infarct protection, starting 24 hours after intravenous administration. This category of clinical drug is a potential prophylactic treatment against skeletal muscle ischemia-reperfusion injury in reconstructive surgery.
在自体肌肉移植中，不可预测的并发症会导致长时间的缺血，从而引起缺血再灌注损伤。作者研究了尼可地尔，一种硝酸酯类和三磷酸腺苷敏感钾通道开放剂，在诱导肌肉皮瓣免受缺血再灌注损伤的围手术期保护中的功效和机制。
将猪（18.2±2.4kg）分为对照组和 8 个治疗组。在给予生理盐水（对照组）和尼可地尔后 0、4、8、12、24、48、72 和 96 小时后，双侧背阔肌皮瓣被抬起。随后，皮瓣经历 4 小时的缺血和 48 小时的再灌注。评估了活力，并使用生化探针研究了尼可地尔诱导的梗塞保护作用。
尼可地尔的保护作用呈双相性。梗塞从 40.2±1.9%（对照组）减少到 27.3±1.7%和 24.0±2.3%（p<0.05），分别在尼可地尔给药后 0 和 4 小时（早期保护）。与对照组相比，尼可地尔给药后 8 至 12 小时，治疗组之间没有差异。梗塞保护作用再次增加（p<0.05），分别在 24 小时（22.4±2.0%）、48 小时（25.1±2.1%）和 72 小时（28.5±2.1%），但在 96 小时（43.9±4.6%）时没有增加（晚期保护）。肌细胞膜和线粒体通道分别在触发和介质机制中发挥核心作用。晚期保护与较低的髓过氧化物酶活性和线粒体钙超载以及较高的三磷酸腺苷含量相关（p<0.05）。
尼可地尔诱导了 48 小时不间断的肌肉梗塞保护作用，在静脉给药后 24 小时开始。这种临床药物类别是重建手术中预防骨骼肌缺血再灌注损伤的潜在治疗方法。
