PURPOSE: In replantation and free-tissue transfer surgeries, partial skin necrosis may occur after temporary interruption of blood supply despite subsequent restoration of blood flow. This is due to ischemia-reperfusion injury, where free radicals generated upon reperfusion cause endothelial cell damage and lead to microcirculatory failure, resulting in skin necrosis. D-amino acid (D-4F), a synthetic mimetic peptide of apolipoprotein A1, has been shown to decrease reactive oxygen species formation and decrease endothelial cell sloughing. We hypothesize that the antioxidant effect of D-4F will decrease the amount of skin necrosis in temporary ischemic flaps.

METHOD: 240 adult male Sprague-Dawley rats were used. A 5x7 cm fasciocutaneous flap based on bilateral inferior epigastric vessels (IEVs) was raised in each rat. The right IEVs were ligated and divided. The left IEVs were skeletonized under 30x operating microscope, clamped using an atraumatic vascular clamp and released after 7 hours. The control group (n=10) received daily intra-peritoneal (IP) injection of sterile saline for 4 days starting on the day prior to surgery. The experimental group (n=10) received D-4F (1mg/kg) rather than saline in the same fashion. Digital photography of each flap was taken on post-operative day #5 at fixed distance. Digital imaging measurement software was used to measure and calculate the percentage of flap necrosis.

RESULTS: No infection occurred. In the control group, each flap showed 40-67% of necrosis with the mean of 53±9.8%. In the experimental group, each flap showed 11-39% of necrosis by with the mean of 22±3.7%. The difference was statistically significant (P<0.0001).

CONCLUSION: D-4F is effective in rats to decrease necrosis of fasciocutaneous flaps induced by ischemia-reperfusion injury. It may be useful in microsurgery involving digital replantation, free-tissue transfer, and salvaging failing free flaps.