Ischemia-reperfusion injury occurs when tissue is reperfused following a prolonged period of ischemia. It is a subject of interest to plastic surgeons involved in replantation, free tissue transfer, and composite tissue allotransplantation, as it can have a significant impact on the overall success of these procedures. The purpose of this article is to review the recent progress in the investigation of ischemia-reperfusion injury in skeletal muscle and skin and to highlight the potential clinical implications of therapeutic interventions aimed at reducing ischemia-reperfusion injury.

Vasospasm and capillary no-reflow are common complications following replantation and free flap transfer. The purpose of the present study was to clarify whether vasospasm and capillary no-reflow which are induced by prolonged warm ischemia/reperfusion can be attenuated by ischemic preconditioning in the vascular isolated cremaster muscle model. Male Sprague-Dawley rats were anesthetized with pentobarbital. Arteriole diameter and capillary perfusion were measured utilizing intravital microscopy. In the control group, the cremasters sustained 4-hour warm global ischemia followed by 60-minute reperfusion. In the ischemic preconditioning group, the cremasters were subjected to one cycle of 45-minute ischemia followed by 15-minute reperfusion prior to 4-hour warm global ischemia followed by 60-minute reperfusion. The results from this experiment showed that ischemic preconditioning significantly attenuated ischemia/reperfusion-induced vasospasm and capillary no-reflow which occur early during reperfusion after prolonged warm ischemia in skeletal muscle. The mechanism of this phenomenon remains to be elucidated.

Necrosis was considered to be the solo mechanism for ischemia/reperfusion (I/R)-induced cell death. Recent evidence from I/R models of the heart, liver, kidney, and brain indicates that apoptosis is a major contributor to I/R-induced cell death. However, evidence of I/R-induced apoptosis in skeletal muscle is sparse and divided. The purpose for the present study was to investigate I/R-induced necrosis and apoptosis in the cells isolated from rat skeletal muscle. A rat gracilis muscle model was used. After surgical preparation, clamps were applied on the vascular pedicle to create 4 h of ischemia and released for 24 h of reperfusion (I/R, n ¼ 10). Clamping was omitted in sham I/R rats (sham I/R, n ¼ 10). The muscle samples were harvested after 24 h of reperfusion for the process of cell isolation. Cells were stained by Propidium Iodide (PI) or Annexin V-FITC or both. Twenty thousand cells from each muscle sample were scanned and analyzed by flow cytometry. The average percentage of live cells was 45 AE 2% in the I/R group versus 65 AE 3% in the sham I/R group (p < 0.01). The average percentage of necrotic cells was 18 AE 1% in I/R versus 12 AE 1% in sham I/R (p < 0.01). The average percentage of apoptotic cells was 40 AE 3% in I/R versus 27 AE 3% in sham I/R (p < 0.01). Our results clearly demonstrated that I/R not only causes necrosis, but also accelerates apoptosis in the cells isolated from rat skeletal muscle.ß

The purpose of this study was to determine microcirculatory effects and response of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion. Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal injection at 30 min prior to reperfusion and the same dose was given immediately after reperfusion. After reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion and endothelial-dependent and -independent vasodilatation were performed. The cremaster muscle was then harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene expression and enzyme activity. Three groups of rats were used: sham-ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with vehicle + I/R group, administration of melatonin significantly enhanced arteriole diameter, improved capillary perfusion, and attenuated endothelial dysfunction in the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm ischemia followed by reperfusion significantly depressed eNOS gene expression and constitutive NOS activity and enhanced iNOS gene expression. Administration of melatonin did not significantly alter NOS gene expression or activity in skeletal muscle after prolonged ischemia and reperfusion. Melatonin provided a significant microvascular protection from reperfusion injury in skeletal muscle. This protection is probably attributable to the free radical scavenging effect of melatonin, but not to its anti-inflammatory effect.

Our results suggest both ischemic preconditioning and intermittent reperfusion are useful techniques for attenuating ischemia/reperfusion injury.