INFUSIONS OF A NOVEL CALCITONIN-GENE-RELATED PEPTIDE (CGRP) DERIVATIVE AT THE TIME OF REPERFUSION TO SALVAGE ISCHEMIC RABBIT SKIN FLAPS

Rabbit epigastric skin flaps were subjected to 21 h of ischaemia at 25 degrees C. In the first 40 min of reperfusion were infused intraarter ially with either Hanks' balanced salt solution (controls), chicken CG RP or a derivative DADA-CGRP. Skin biopsies and blood specimens were t aken immediately before and after 1-h reperfusion. The aim was to obse rve the effect of CGRP derivatives on compromised skin-flap survival a nd to help elucidate the critical biochemical mechanisms. It was found that chicken CGRP and DADA-CGRP produced a dose-dependent increase in blood flow, significant at and above 0.1 mu g/kg, but only the 0.1 mu g/kg DADA-CGRP infusion produced a statistically significant increase in flap survival (75.1%) as compared with controls (41.6%). CGRP infu sions caused significantly more rapid restoration of tissue ATP levels and resulted in a smaller rise in blood thromboxane as compared with controls. However, CGRP caused no significant change in the tissue lev els of myeloperoxidase, a measure of neutrophil infiltration, and lipi d peroxidation, an indicator of free-radical activity. It is concluded that intraarterial CGRP infusions to ischaemic flaps at the time of r eperfusion are indicated. However, an ideal infusion solution would al so need to counteract free radicals and neutrophils which are believed to also play a major role in the inflammatory response leading to fla p failure.