THE PROTECTIVE EFFECT OF L-ARGININE ON ISCHEMIA-REPERFUSION INJURY INRAT SKIN FLAPS

The objective of this study was to examine whether the administration of L-arginine, a precursor of nitric oxide and substrate of nitric oxi de synthase, prior to reperfusion could lead to decrease in neutrophil -mediated tissue injury and improved flap survival. Epigastric island skin flaps were elevated in 70 rats and rendered ischemic. Thirty minu tes prior to reperfusion, the rats were treated with intraperitoneal s aline (n = 15), L-arginine (n = 15), D-arginine (n = 15), or N-omega-n itro-L-arginine methylester plus L-arginine in equimolar amounts (n = 15). Flap survival at 7 days and neutrophil counts at 24 hours were ev aluated. Flap necrosis as expected in the sham group of animals (n = 1 0) was 0.0 percent, while the control (saline-treated) animals had 59. 6 percent necrosis. Animals treated with L-arginine demonstrated a sig nificant decrease in flap necrosis to 12.7 percent. This protective ef fect was almost completely negated by N-omega-nitro-L-arginine methyle ster, which significantly increased flap necrosis to 49.3 percent and was much less pronounced with D-arginine (28.6 percent). Neutrophil co unts were significantly decreased in flaps from L-arginine-treated and sham animals versus both saline and N-omega-nitro-L-arginine methyles ter-treated groups. We conclude that administration of L-arginine Drie r to reperfusion can significantly reduce the extent of flap necrosis and flap neutrophil counts due to ischemia reperfusion injury. This pr otective effect is completely negated by nitric oxide synthase inhibit ion. Since L-arginine reduces the number of neutrophils within the fla p and the extent of flap necrosis only in the presence of active nitri c oxide synthase, we hypothesize that this protective effect of L-argi nine on ischemia-reperfusion injury is secondary to a nitric oxide-med iated suppression of neutrophil-mediated injury.