Calcitonin gene-related peptide improves skin flap survival and tissue inflammation.
The effects of systemic administration of calcitonin gene-related peptide (CGRP) on survival and inflammation of experimental skin flaps subjected to prolonged arterial ischemia were studied. An island groin flap 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. Following 12 h of ischemia, three flaps (30%) survived, compared with 100% survival of the control group. In the second part of the study the effects of CGRP on flap survival were assessed. Eighty flaps were rendered ischemic 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. Administration of CGRP (10(-7) M) significantly increased the number of flaps surviving compared with the control. The effect of systemic pretreatment of the animals with the CGRP receptor antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Flap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected 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. Myeloperoxidase (MPO) analysis was used as marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h MPO accumulation in the flap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increase of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on survival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.
Gherardini
G
G
Department of Surgery, Karolinska Hospital and Institutet, Stockholm, Sweden. ggherardini@usa.net
Gürlek
A
A
Milner
S M
SM
Matarasso
A
A
Evans
G R
GR
Jernbeck
J
J
Lundeberg
T
T
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000627:therapeutic use*; D003250:Constriction; D005263:Femoral Artery / Q000502:physiology; D006085:Graft Survival; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000201:enzymology; D013524:Surgical Flaps; D013997:Time Factors
D009195:Peroxidase; D015740:Calcitonin Gene-Related Peptide