Pharmacologic Prophylactic Treatment for Perioperative Protection of Skeletal Muscle from Ischemia-Reperfusion Injury in Reconstructive Surgery

Background: 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. Methods: 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. Results: 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). Conclusions: 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. (Plast. Reconstr. Surg. 131: 473, 2013.)