Effects of calcitonin gene-related peptide on tissue survival, blood flow and neutrophil recruitment in experimental skin flaps.

Local administration of calcitonin gene-related peptide (CGRP) has been shown to improve tissue survival in surgical skin flaps. Moreover, topical CGRP has been demonstrated to exert anti-inflammatory effects in different animal models of skin inflammation. The aim of the present study was to establish whether systemic treatment with low doses of CGRP may improve survival and reduce neutrophil accumulation in surgical skin flaps. Using a well-established dorsal skin-flap model in the rat, we found that intraperitoneal (i.p.) pretreatment with low doses of CGRP dose-dependently increased flap survival. Thus, in untreated animals flap survival at day 7 after surgery was 42%, as compared to 44%, 60%, 69% and 73% survival after a single preoperative i.p. injection of 10(-15), 10(-12), 10(-9) and 10(-6) mol CGRP, respectively (P < 0.05 versus control for the three highest doses). The three effective doses had no detectable effects on either flap blood flow (laser Doppler) or mean arterial blood pressure. On the other hand, 5 x 10(-9) mol CGRP i.p. significantly reduced the marked surgery-induced accumulation of flap myeloperoxidase (a marker for neutrophil recruitment) without affecting the circulating neutrophil count. Taken together, our findings demonstrate that low systemic doses of CGRP can cause a major improvement in skin-flap survival in the rat, possibly via inhibition of surgically induced neutrophil recruitment.