Involvement of Neutrophils in Ischemia-Reperfusion Injury of Inguinal Island Skin Flaps in Rats

Abstract

Increased production of oxygen free radicals and infiltration of neutrophils into tissue subjected to ischemia-reperfusion have emphasized that neutrophils play a direct role in the development of injury. The present study was designed to elucidate the effect of FK506, a new immunosuppressive drug, on 11 hours of complete ischemia and reperfusion of the inguinal island skin flaps in rats. Group 1 (n = 10) control animals underwent ischemia and reperfusion and no treatment. Group 2 (n = 10) animals received FK 506 0.3 mg/kg/day, and group 3 (n = 9) animals received 0.5 mg/kg/day intramuscularly for 3 days before the ischemia. The effect of the drug was evaluated by measuring flap survival and tissue malondialdehyde content and myeloperoxidase activity and also by histopathologic examination of the skin specimens taken at the 1st and 24th hour after reperfusion. The survival of flaps controlled for 7 days was found to be significantly improved in group 2 (65.0 +/- 10.93 percent) and group 3 (93 +/- 6.25 percent) when compared with the control group (14 +/- 10.12 percent) (p < 0.04 and p < 0.0001). The tissue contents of malondialdehyde and activities of myeloperoxidase were significantly lower in groups 2 and 3 than in the control group. Three days of pretreatment with FK506 significantly reduced neutrophil infiltration in groups treated with either of the doses. These results showed that neutrophils play an important role in island flap survival associated with ischemia-reperfusion injury. Increased neutrophil infiltration was found related with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and the increase in malondialdehyde, myeloperoxidase, and neutrophil infiltration were improved by FK506 pretreatment, a neutrophil modulating agent.

Montelukast Protects Axial Pattern Rat Skin Flaps Against Ischemia/Reperfusion Injury

“…Neutrophils activated via cytokine stimulation play an integral role in I/R injury [27][28][29]. In this study, tissue neutrophil counts were lower when the viable flap area was larger, which is similar to previous studies [8,14].…”

“…This flap model has been widely used in experimental studies on I/R injury and skin flap survival [1,2,8,12,13,29,31]. In the literature, flap sizes range between 4 to 7 cm in length and 2.5 to 4 cm in width [1,2,8,12,13,29,31].…”

The Impact of Lidocaine on Flap Survival Following Reperfusion Injury

“…The beginning and progression of tissue damage in an inflammatory condition is influenced by the release of lipid mediators from neutrophils, along with the release of toxic free radical, proteolytic enzyme, cationic proteins, and many vasoactive transmitters [12]. The increase in MDA and MPO levels is dependent on reperfusion injury; while MDA level reflects the elevated necrosis rate, MPO level demonstrates the elevated neutrophil accumulation [15]. As treatment flaps displayed an increase in survival, the level of lipid degradation products showed a decrease, but the neutrophil infiltration was not reduced.…”

Establishment of a Cutaneous Flap Animal Model to Study Platelet and Leukocyte Dynamics After Ischemia-Reperfusion Injury

“…3,5 Inflammatory mediators accumulate, neutrophils and platelets are recruited and activated, vascular permeability increases, and oxygen free radicals and proteolytic enzymes are released. 7 The end result can be cellular necrosis in postischemic tissues. Increased platelet and leukocyte activity has been implicated in ischemiareperfusion injury in various tissues, such as the liver, heart, and gastrointestinal tract.…”