CALCITONIN-GENE-RELATED PEPTIDE IMPROVES SKIN FLAP SURVIVAL AND TISSUE INFLAMMATION

The effects of systemic administration of calcitonin gene-related pept ide (CGRP) on survival and inflammation of experimental skin flaps sub jected to prolonged arterial ischemia were studied. An island groin fl ap was elevated in the rat. The femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a group of 10 sham-operated control animals, the femoral artery was not occluded. After ischemia, blood flow was restored and flap survival evaluated at day 7. Followin g 12 h of ischemia, three flaps (30%) survived, compared with 100% sur vival of the control group. In the second part of the study the effect s of CGRP on flap survival were assessed. Eighty flaps were rendered i schemic for 12 h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or Saline (control) at the end of the ischemia period. Admi nistration of CGRP (10(-7) M) significantly increased the number of fl aps surviving compared with the control. The effect of systemic pretre atment of the animals with the CGRP receptor antagonist CGRP8(-37), fo llowed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Fl ap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subj ected to arterial ischemia for 12 h, and received systemic CGRP (10(-7 ) M), or saline at the end of the period of ischemia. The animals were sacrificed at 24 h and flap tissue samples were obtained. Myeloperoxi dase (MPO) analysis was used as marker of neutrophil accumulation. CGR P (10(-7) M) significantly reduced the 24 h MPO accumulation in the fl ap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increa se of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on su rvival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.