INVOLVEMENT OF NEUTROPHILS IN ISCHEMIA-REPERFUSION INJURY OF INGUINALISLAND SKIN FLAPS IN RATS

Increased production of oxygen free radicals and infiltration of neutr ophils into tissue subjected to ischemia-reperfusion have emphasized t hat neutrophils play a direct role in the development of injury. The p resent study was designed to elucidate the effect of FK506, a new immu nosuppressive drug, on 11 hours of complete ischemia and reperfusion o f the inguinal island skin flaps in rats. Group 1 (n = 10) control ani mals underwent ischemia and reperfusion and no treatment. Group 2 (n = 10) animals received FR 506 0.3 mg/kg/day, and group 3 (n = 9) animal s received 0.5 mg/kg/day intramuscularly for 3 days before thr ischemi a. 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 9 (93 +/- 6.25 percent) when compared with the c ontrol group (14 +/- 10.12 percent) (p < 0.04 and p < 0.0001). The tis sue contents of malondialdehyde and activities of myeloperoxidase were significantly lower in groups 2 and 3 than in the control group. Thre e days of pretreatment with FK506 significantly reduced neutrophil inf iltration in groups treated with either of the doses. These results sh owed that neutrophils play an important role in island flap survival a ssociated with ischemia-reperfusion injury. Increased neutrophil infil tration was found related with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and the increase in malondialdehyde, m yeloperoxidase, and neutrophil infiltration were improved by FK506 pre treatment, a neutrophil modulating agent.