Improved survival of murine island skin flaps by prevention of reperfusion injury.
BACKGROUND
Studies have demonstrated that blocking a single specificity of self-reactive immunoglobulin M with a 12-amino acid peptide mimic of the antigen of immunoglobulin M can attenuate murine intestinal and skeletal muscle injury following ischemia and reperfusion. The aim of this study was to ascertain whether peptide (P8) had protective effects in an axial island skin flap model, where tissue loss is attributed to ischemia-reperfusion injury.


METHODS
Dorsal lateral thoracic artery island skin flaps (3.5 x 1.5 cm) were elevated in 82 male C57BL/6 mice and rendered ischemic for 10 hours by placing a 7-mm microclamp on the vascular pedicle followed by 7 days of reperfusion. Group I (n = 7), the sham group, had no clamp placed. Group II (n = 21) had clamp placement but no other treatment. Thirty minutes before clamp placement, group III (n = 18) received 0.25 cc of saline intravenously, group IV (n = 18) received 25 microg/0.25 cc P8 peptide, and group V (n = 7) received 25 microg/0.25 cc random 12-mer peptide. Animals in group VI (n = 11) underwent two cycles of 20 minutes of ischemic preconditioning before 10 hours of ischemia. After 1 week of reperfusion, percent necrosis was measured and results were compared using analysis of variance and an unpaired t test.


RESULTS
In animals treated with P8 peptide, flap necrosis was 14.61 +/- 2.77 percent. This represents a statistically significant, 56 percent reduction in flap necrosis compared with controls (p < 0.001).


CONCLUSIONS
These data demonstrate that prevention of ischemia-reperfusion injury with P8 peptide produces a significant reduction in necrosis of treated flaps.
Tatlidede
Soner H
SH
Boston, Mass. From the Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, and Brigham and Women's Hospital, Harvard Medical School.
Murphy
Adrian D
AD
McCormack
Michael C
MC
Nguyen
John T
JT
Eberlin
Kyle R
KR
Randolph
Mark A
MA
Moore
Francis D
FD
Austen
William G
WG
D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010455:Peptides / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology
C541129:P8 peptide; D010455:Peptides